bluuebunny/crossref_metadata_2025 huggingface dataset:
New Insights into the Understanding of High-Pressure Air Injection (HPAI): The Role of the Different Chemical Reactions
Authors: Gutiérrez Dubert , Moore Gord , Mallory Don , Ursenbach Matt , Mehta Raj , Bernal Andrea
Published: October 2024

High-pressure air injection (HPAI) is an enhanced oil recovery process in which compressed air is injected into deep, light oil reservoirs, with the expectation that the oxygen in the injected air will react with a fraction of the reservoir oil at an elevated temperature to produce carbon dioxide. The different chemical reactions taking place can be grouped into oxygen addition, thermal cracking, oxygen-induced cracking, and bond scission reactions. The latter reactions involve the combustion of a flammable vapor as well as the combustion of solid fuel, commonly known as “coke”. Since stable peak temperatures observed during HPAI experiments are typically below 300 °C, it has been suggested that thermal cracking and combustion of solid fuel may not be important reaction mechanisms for the process. The objective of this work is to assess the validity of that hypothesis. Therefore, this study makes use of different oxidation and combustion HPAI experiments, which were performed on two different light oil reservoir samples. Modeling of those tests indicate that thermal cracking is not an important reaction mechanism during HPAI and can potentially be ignored. The work also suggests that the main fuel consumed by the process is a flammable vapor generated by the chemical reactions. This represents a shift from the original in situ combustion paradigm, which is based on the combustion of coke.
Prevalence and Predictors of Potentially Inappropriate Prescribing in Older People Receiving Home Health Care in Saudi Arabia According to the American Geriatrics Society Beers Criteria 2019
Authors: Khawagi Wael Y. , Alshehri Abdullah A. , Alghuraybi Ziyad M. , Alashaq Abdullah K. , Alziyadi Rayan A. , Fathelrahman Ahmed I.
Published: October 2024

Background/Objectives: Potentially inappropriate prescribing (PIP) is a common health problem in older adults and is associated with negative health outcomes such as the occurrence of adverse drug events. Several studies have been conducted in different countries and settings to assess the prevalence of PIP, including in Home Care Services. However, data on the prevalence of PIP in home-care services in Saudi Arabia are limited. This study aimed to evaluate PIP use among older patients receiving home healthcare services in Saudi Arabia and to identify the predictors and commonly implicated medications.; Methods: A cross-sectional study was conducted over an 8-month period between January and August 2023. Data were collected from the medical records of patients older than 65 years who were currently receiving home health care services at King Faisal Hospital in Taif City, Saudi Arabia. PIPs were identified using the 2019 updated Beers Criteria.; Results: A total of 375 patients were included. Out of these, 285 PIPs were identified, of which 219 patients (58.4%) received at least one PIP. The most common therapeutic class associated with the PIPs was gastrointestinal medications (66.3%). Patient age and number of medications were significant predictors of PIP.; Conclusions: Our study found a high prevalence of PIP among elderly patients receiving home health care in Taif, Saudi Arabia. This study highlights the need for improved patient data automation and implementation of the Beers criteria to prevent PIPs in the future.
Kilometer-Scale Precipitation Forecasting Utilizing Convolutional Neural Networks: A Case Study of Jiangsu’s Coastal Regions
Authors: Cai Ninghao , Sun Hongchuan , Yan Pengcheng
Published: October 2024

High-resolution precipitation forecasts play a pivotal role in formulating comprehensive disaster prevention and mitigation plans. As spatial resolution enhances, striking a balance between computation, storage, and simulation accuracy becomes imperative to ensure optimal cost-effectiveness. Convolutional neural networks (CNNs), a cornerstone of deep learning, are examined in this study for their downscaling capabilities in precipitation simulation. During a precipitation event on 23 June 2022, in Jiangsu Province, China, distinct rain belts emerged in both southern and northern Jiangsu, precisely captured by a numerical model (the Weather Research and Forecasting, WRF) with a 3 km spatial resolution. Specifically, precipitation was prevalent in northern Jiangsu from 00:00 to 11:00 Beijing Time (BJT), transitioning to southern Jiangsu from 12:00 to 23:00 BJT on the same day. Upon dynamic downscaling, the model reproduced precipitation in these periods with an average error of 12.35 mm at 3 km and 12.48 mm at 1 km spatial resolutions. Employing CNN technology for statistical downscaling to a 1 km spatial resolution, samples from the initial period were utilized for training, while those from the subsequent period served for validation. Following dynamic downscaling, CNNs with four, five, six, and seven layers exhibited average errors of 8.86 mm, 8.93 mm, 9.71 mm, and 9.70 mm, respectively, accompanied by correlation coefficients of 0.550, 0.570, 0.574, and 0.578, respectively. This analysis indicates that for this precipitation event, a shallower CNN depth yields a lower average error and correlation coefficient, whereas a deeper architecture enhances the correlation coefficient. By employing deep network architectures, CNNs are capable of capturing nonlinear patterns and subtle local features from complex meteorological data, thereby providing more accurate predictions during the downscaling process. Leveraging faster computation and reduced storage requirements, machine learning has demonstrated immense potential in high-resolution forecasting research. There is significant scope for advancing technologies that integrate numerical models with machine learning to achieve higher-resolution numerical forecasts.
Spatial–Temporal Patterns in the Enteric Pathogen Contamination of Soil in the Public Environments of Low- and Middle-Income Neighborhoods in Nairobi, Kenya
Authors: Gutema Fanta D. , Okoth Bonphace , Agira John , Amondi Christine S. , Busienei Phylis J. , Simiyu Sheillah , Mberu Blessing , Sewell Daniel , Baker Kelly K.
Published: October 2024

Public spaces in countries with limited societal development can be contaminated with feces containing pathogenic microbes from animals and people. Data on contamination levels, spatial distribution, and the diversity of enteric pathogens in the public settings of low- and middle-income neighborhoods are crucial for devising strategies that minimize the enteric infection burden. The objective of this study was to compare spatial–temporal differences in the detection rate and diversity of enteric pathogens in the public spaces of low- and middle-income neighborhoods of Nairobi, Kenya. TaqMan array card (TAC) molecular assays were employed to analyze soil samples for 19 enteropathogens, along with a selective bacterial culture for pathogenic Enterobacteriaceae. An observational assessment was conducted during every site visit to document the hygienic infrastructure and sanitation conditions at the sites. We detected at least one pathogen in 79% (127/160) and ≥2 pathogens in 67.5% (108/160) of the soil samples tested. The four most frequently detected pathogens were EAEC (67.5%), ETEC (59%), EPEC (57.5%), and STEC (31%). The detection rate (91% vs. 66%) and mean number of enteric pathogens (5 vs. 4.7) were higher in low-income Kibera than in middle-income Jericho. The more extensive spatial distribution of pathogens in Kibera resulted in increases in the detection of different enteric pathogens from within-site (area < 50 m2) and across-site (across-neighborhood) movements compared to Jericho. The pathogen detection rates fluctuated seasonally in Jericho but remained at sustained high levels in Kibera. While better neighborhood conditions were linked with lower pathogen detection rates, pathogenic E. coli remained prevalent in the public environment across both neighborhoods. Future studies should focus on identifying how the sources of pathogen contamination are modified by improved environmental sanitation and hygiene and the role of these contaminated public environments in enteric infections in children.
Analyzing Social Support from Facebook on Viral Suppression among Young Black Men Who Have Sex with Men Living with HIV: A Pilot Study
Authors: Friedman Eleanor E. , Del Vecchio Natascha , Mason Joseph A. , Devlin Samantha A. , Ridgway Jessica P. , Schneider John A.
Published: October 2024

Social support has been associated with viral suppression among persons living with HIV (PWH). We examined cross-sectional data from young Black men who have sex with men to see if sociodemographic factors, medical history, and egocentric Facebook social support measures are related to viral suppression. Differences between participants were examined using Chi-square, Fisher’s exact, or Wilcoxon Rank Sum Tests, with significance set at p = 0.10. Degree centrality (p = 0.074) and Eigenvector centrality (p = 0.087) were significant, indicating that PWH with unsuppressed viral loads had more social connections. These results contrast prior studies in the literature. Further research on online social support for PWH is needed.
Early Socio-Emotional Difficulty as a Childhood Barrier to the Expected Benefits of Active Play: Associated Risks for School Engagement in Adolescence
Authors: Kosak Laurie-Anne , Harandian Kianoush , Bacon Simon L. , Archambault Isabelle , Correale Luca , Pagani Linda S.
Published: October 2024

Active play allows children to develop social and cognitive skills, which could lead to higher school engagement. Little is known about the role of child socioemotional difficulty in these associations. This study aims to examine the interaction between active play and socioemotional difficulty in childhood and their prospective association with academic engagement in adolescence. The participants were 4537 children (51.1% boys) who were longitudinally followed, between ages 6 and 14 years, from the National Longitudinal Study on Children and Youth (NLSCY), Canada. Active play (weekly organized sport and unstructured physical activity outside of school hours) and child behavior (hyperactivity, anxiety, and relational difficulties) were reported by mothers for their children at age 6 years. Academic engagement was self-reported at age 14 years. Unstructured physical activity predicted lower subsequent school engagement for boys (β = −0.057, p < 0.05). Boys with high anxiety symptoms and high relational aggression who participated in more unstructured physical activity in childhood were subsequently less engaged in school (respectively, β = −0.066, p < 0.05 and β = −0.062, p < 0.05). Girls who partook in more organized sports showed lower school engagement in adolescence when they had high anxiety symptoms (β = −0.067, p < 0.05). Although past studies have highlighted the contribution of active play to school engagement, certain socioemotional difficulties could impede the child’s ability to reap its benefits.
Lesbian and Gay Population, Work Experience, and Well-Being: A Ten-Year Systematic Review
Authors: Lacatena Marina , Ramaglia Ferdinando , Vallone Federica , Zurlo Maria Clelia , Sommantico Massimiliano
Published: October 2024

Despite an increase in the promotion of equal opportunities at work, there is still persistent discrimination against lesbian and gay (LG) workers. In this vein, this study aimed to systematically review the research investigating the peculiarities of the work experience of LG people, particularly considering the theoretical frameworks in the approach to sexual minorities’ work-related issues, as well as individual and contextual variables influencing the work experience and the impact they may have on health and well-being. We explored the PsycArticles, EMBASE, Scopus, and Web of Science electronic databases and the EBSCOHost (PsycInfo, Psychology and Behavioral Sciences Collection) scholarly search engine, between 01/01/2013 to 01/03/2023, with regards to the search terms “lgb*”, “gay*”, “lesbian*”, “homosexual*”, and “sexual minorit*”, associated with “employee*”, ”personnel”, “worker*”, and “staff”, and with “workplace”, “work”, “job”, “occupation”, “employment”, and “career”. Data were narratively synthesized and critically discussed. Of the 1584 potentially eligible articles, 140 papers contributed to this systematic review. Five main theoretical frameworks were identified: (a) minority stress, (b) sexual prejudice and stigma, (c) queer and Foucauldian paradigms, (d) social identity theories, and (e) intersectionality. Furthermore, significant individual (e.g., outness, disclosure, and work–family conflict) and contextual (e.g., heterosexist and heteronormative workplace climate and culture) variables influencing LG people’s work experience were identified. This review highlights the need to develop a unified theoretical model for the construction of specific measurement tools to assess the work experience of LG people and for the implementation of interventions aimed at minimizing the effects of stigma in work contexts.
Mechanism of Intracellular Elemental Sulfur Oxidation in Beggiatoa leptomitoformis, Where Persulfide Dioxygenase Plays a Key Role
Authors: Rudenko Tatyana S. , Trubitsina Liubov I. , Terentyev Vasily V. , Trubitsin Ivan V. , Borshchevskiy Valentin I. , Tishchenko Svetlana V. , Gabdulkhakov Azat G. , Leontievsky Alexey A. , Grabovich Margarita Yu.
Published: October 2024

Representatives of the colorless sulfur bacteria of the genus Beggiatoa use reduced sulfur compounds in the processes of lithotrophic growth, which is accompanied by the storage of intracellular sulfur. However, it is still unknown how the transformation of intracellular sulfur occurs in Beggiatoa representatives. Annotation of the genome of Beggiatoa leptomitoformis D-402 did not identify any genes for the oxidation or reduction of elemental sulfur. By searching BLASTP, two putative persulfide dioxygenase (PDO) homologs were found in the genome of B. leptomitoformis. In some heterotrophic prokaryotes, PDO is involved in the oxidation of sulfane sulfur. According to HPLC-MS/MS, the revealed protein was reliably detected in a culture sample grown only in the presence of endogenous sulfur and CO2. The recombinant protein from B. leptomitoformis was active in the presence of glutathione persulfide. The crystal structure of recombinant PDO exhibited consistency with known structures of type I PDO. Thus, it was shown that B. leptomitoformis uses PDO to oxidize endogenous sulfur. Additionally, on the basis of HPLC-MS/MS, RT-qPCR, and the study of PDO reaction products, we predicted the interrelation of PDO and Sox-system function in the oxidation of endogenous sulfur in B. leptomitoformis and the connection of this process with energy metabolism.
Deciphering Immunotoxicity in Animal-Derived Biomaterials: A Genomic and Bioinformatics Approach
Authors: Lian Huan , Liu Yu , Ke Linnan , Han Qianqian
Published: October 2024

Immunotoxicity evaluation has been crucial in preclinical testing for implantable animal-derived biomaterials due to their prolonged contact with the human body, which requires stringent safety assessments. By creating experimental models with varying levels of immunotoxicity, this study reveals the decisive role of decellularization treatment in diminishing the immunogenicity of materials, thus ensuring clinical safety. Employing cutting-edge differential gene expression analysis, the research not only accurately quantifies gene expression alterations in immune responses but also, through pathway enrichment analysis, identifies gene networks associated with oncogenesis. This offers novel insights into the mechanisms of immune responses following biomaterial implantation. Additionally, the study highlights the importance of developing highly sensitive immunotoxicity testing methods and validates the efficacy of high-throughput sequencing and bioinformatics tools in assessing biomaterial safety, providing robust scientific support for future preclinical evaluations.
MetaWise: Combined Feature Selection and Weighting Method to Link the Serum Metabolome to Treatment Response and Survival in Glioblastoma
Authors: Tasci Erdal , Popa Michael , Zhuge Ying , Chappidi Shreya , Zhang Longze , Cooley Zgela Theresa , Sproull Mary , Mackey Megan , Kates Heather R. , Garrett Timothy J. , Camphausen Kevin , Krauze Andra V.
Published: October 2024

Glioblastoma (GBM) is a highly malignant and devastating brain cancer characterized by its ability to rapidly and aggressively grow, infiltrating brain tissue, with nearly universal recurrence after the standard of care (SOC), which comprises maximal safe resection followed by chemoirradiation (CRT). The metabolic triggers leading to the reprogramming of tumor behavior and resistance are an area increasingly studied in relation to the tumor molecular features associated with outcome. There are currently no metabolomic biomarkers for GBM. Studying the metabolomic alterations in GBM patients undergoing CRT could uncover the biochemical pathways involved in tumor response and resistance, leading to the identification of novel biomarkers and the optimization of the treatment response. The feature selection process identifies key factors to improve the model’s accuracy and interpretability. This study utilizes a combined feature selection approach, incorporating both Least Absolute Shrinkage and Selection Operator (LASSO) and Minimum Redundancy–Maximum Relevance (mRMR), alongside a rank-based weighting method (i.e., MetaWise) to link metabolomic biomarkers to CRT and the 12-month and 20-month overall survival (OS) status in patients with GBM. Our method shows promising results, reducing feature dimensionality when employed on serum-based large-scale metabolomic datasets (University of Florida) for all our analyses. The proposed method successfully identified a set of eleven serum biomarkers shared among three datasets. The computational results show that the utilized method achieves 96.711%, 92.093%, and 86.910% accuracy rates with 48, 46, and 33 selected features for the CRT, 12-month, and 20-month OS-based metabolomic datasets, respectively. This discovery has implications for developing personalized treatment plans and improving patient outcomes.
Interplay of Cellular Nrf2/NF-κB Signalling after Plasma Stimulation of Malignant vs. Non-Malignant Dermal Cells
Authors: Manzhula Kristina , Rebl Alexander , Budde-Sagert Kai , Rebl Henrike
Published: October 2024

Skin cancer is one of the most common malignancies worldwide. Cold atmospheric pressure Plasma (CAP) is increasingly successful in skin cancer therapy, but further research is needed to understand its selective effects on cancer cells at the molecular level. In this study, A431 (squamous cell carcinoma) and HaCaT (non-malignant) cells cultured under identical conditions revealed similar ROS levels but significantly higher antioxidant levels in unstimulated A431 cells, indicating a higher metabolic turnover typical of tumour cells. HaCaT cells, in contrast, showed increased antioxidant levels upon CAP stimulation, reflecting a robust redox adaptation. Specifically, proteins involved in antioxidant pathways, including NF-κB, IκBα, Nrf2, Keap1, IKK, and pIKK, were quantified, and their translocation level upon stimulation was evaluated. CAP treatment significantly elevated Nrf2 nuclear translocation in non-malignant HaCaT cells, indicating a strong protection against oxidative stress, while selectively inducing NF-κB activation in A431 cells, potentially leading to apoptosis. The expression of pro-inflammatory genes like IL-1B, IL-6, and CXCL8 was downregulated in A431 cells upon CAP treatment. Notably, CAP enhanced the expression of antioxidant response genes HMOX1 and GPX1 in non-malignant cells. The differential response between HaCaT and A431 cells underscores the varied antioxidative capacities, contributing to their distinct molecular responses to CAP-induced oxidative stress.
The Translatome Map: RNC-Seq vs. Ribo-Seq for Profiling of HBE, A549, and MCF-7 Cell Lines
Authors: Kozlova Anna , Sarygina Elizaveta , Ilgisonis Ekaterina , Tarbeeva Svetlana , Ponomarenko Elena
Published: October 2024

Gene expression is a tightly regulated process that involves multiple layers of control, including transcriptional, post-transcriptional, and translational regulation. To gain a comprehensive understanding of gene expression dynamics and its functional implications, it is crucial to compare translatomic, transcriptomic, and proteomic data. The two most common analysis methods, Ribo-seq and RNC-Seq, were used to analyze the translatome of the same sample, whose datasets were downloaded from the TranslatomeDB database. The resulting translatome maps obtained for three cell lines (HBE, A549, and MCF-7) using these two methods were comparatively analyzed. The two methods of translatome analysis were shown to provide comparable results and can be used interchangeably. The obtained mRNA translation patterns were annotated in the transcriptome and proteome context for the same sample, which may become the basis for the reconstruction of the molecular mechanisms of pathological process development in the future.
Myo-Inositol and D-Chiro-Inositol Reduce DHT-Stimulated Changes in the Steroidogenic Activity of Adult Granulosa Cell Tumors
Authors: Wojciechowska Anna Maria , Zając Paulina , Gogola-Mruk Justyna , Kowalik Magdalena Karolina , Ptak Anna
Published: October 2024

Considering the properties of myo-inositol (MI) and D-chiro-inositol (DCI), which are well known in polycystic ovary syndrome therapy, and the limitations of adult granulosa cell tumor (AGCT) treatment, especially for androgen-secreting tumors, we studied the role of MI and DCI in the androgen-rich environment of AGCTs. For this purpose, we analyzed the mRNA expression of steroidogenic genes and the secretion of progesterone (P4) and 17β-estradiol (E2) in an unstimulated and/or dihydrotestosterone (DHT)-stimulated environment under MI and DCI influence. Thus, we used the HGrC1 and KGN cell lines as in vitro models of healthy and cancerous granulosa cells. We found that DHT, the most potent androgen, increased E2 secretion and steroidogenic acute regulatory protein (StAR) and cytochrome P450 side-chain cleavage gene (CYP11A1) mRNA expression without affecting 450 aromatase (CYP19A1) in AGCTs. However, after the MI and DCI treatment of KGN cells, both compounds strongly reduced StAR and CYP11A1 expression. Interestingly, in DHT-stimulated KGN cells, only DCI alone and its cotreatment with MI reduced both CYP11A1 mRNA and E2 secretion. These findings suggest that CYP11A1 is responsible for the antiestrogenic effect of DCI in the androgen-rich environment of AGCTs. Therefore, MI and DCI could be used as effective agents in the adjuvant treatment of AGCT, but further detailed studies are needed.
Selenomethionine Mitigates Effects of Nocardia cyriacigeorgica-Induced Inflammation, Oxidative Stress, and Apoptosis in Bovine Mammary Epithelial Cells
Authors: Assabayev Talgat , Han Jinge , Bahetijiang Halihaxi , Abdrassilova Venera , Khan Muhammad Asfandyar , Barkema Herman W. , Liu Gang , Kastelic John P. , Zhou Xueying , Han Bo
Published: October 2024

Nocardia cyriacigeorgica causes bovine mastitis, reduces milk quantity and quality, and is often resistant to antimicrobials. Selenomethionine (SeMet) is a form of selenium, which reduces reactive oxygen species (ROS)-mediated apoptosis and intramammary infections. However, the protective effects of SeMet on N. cyriacigeorgica-infected bovine mammary epithelial cells (bMECs) are unclear. The objective of this study was to evaluate whether SeMet mitigated N. cyriacigeorgica-induced inflammatory injury, oxidative damage and apoptosis in bMECs. Cells were cultured with or without being pretreated with 40 µM of SeMet for 12 h, then challenged with N. cyriacigeorgica (multiplicity of infection = 5:1) for 6 h. Although N. cyriacigeorgica was resistant to lincomycin, erythromycin, enrofloxacin, penicillin, amoxicillin, cephalonium, cephalexin, and ceftriaxone, 40 μM SeMet increased cell viability and inhibited lactate dehydrogenase release in infected bMECs. Furthermore, N. cyriacigeorgica significantly induced mRNA production and protein expression of TNF-α, IL-1β, IL-6, and IL-8 at 6 h. Cell membrane rupture, cristae degeneration and mitochondria swelling were evident with transmission electron microscopy. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activities were down-regulated after 3, 6, or 12 h, whereas malondialdehyde (MDA) and ROS contents were significantly upregulated, with cell damage and apoptosis rapidly evident (the latter increased significantly in a time-dependent manner). In contrast, bMECs pretreated with 40 μM SeMet before infection, SOD, and GSH-px activities were upregulated (p < 0.05); MDA and ROS concentrations were downregulated (p < 0.05), and apoptosis was reduced (p < 0.05). In conclusion, 40 μM SeMet alleviated inflammation, oxidative stress and apoptosis induced by N. cyriacigeorgica in bMECs cultured in vitro.
Triterpenoid Saponins and Flavonoid Glycosides from the Flower of Camellia flavida and Their Cytotoxic and α-Glycosidase Inhibitory Activities
Authors: Ma Siyuan , Wu Yuxin , Min Hanfeng , Ge Li , Yang Kedi
Published: October 2024

Camellia flavida var. flavida, commonly known as “Jinhua Tea”, has its flowers and leaves traditionally utilized as tea and functional food sources. However, there is limited knowledge about its bioactive components and their biological activities. This study isolated ten previously unidentified glycoside compounds from the flowers of Camellia flavida, including three oleanane-type triterpenoid saponins (compounds 1–3) and seven flavonoid glycosides (compounds 4–10), collectively named flavidosides A–J. This study assessed the cytotoxicity of these compounds against a panel of human cancer cell lines and their α-glucosidase inhibitory activities. Notably, flavidoside C showed significant cytotoxicity against BEL-7402 and MCF-7 cell lines, with IC50 values of 4.94 ± 0.41 and 1.65 ± 0.39 μM, respectively. Flavidoside H exhibited potent α-glucosidase inhibitory activity, with an IC50 value of 1.17 ± 0.30 mM. These findings underscore the potential of Camellia flavida in the development of functional foods.
Impacts of Hyperglycemia on Epigenetic Modifications in Human Gingival Fibroblasts and Gingiva in Diabetic Rats
Authors: Kojima Kento , Nakamura Nobuhisa , Hayashi Airi , Kondo Shun , Miyabe Megumi , Kikuchi Takeshi , Sawada Noritaka , Saiki Tomokazu , Minato Tomomi , Ozaki Reina , Sasajima Sachiko , Mitani Akio , Naruse Keiko
Published: October 2024

Periodontal disease is considered one of the diabetic complications with high morbidity and severity. Recent studies demonstrated the involvement of the epigenome on diabetic complications. Histone modifications change chromatin architecture and gene activation. Histone modifications have been reported to alter chromatin structure and regulate gene transcription. In this study, we investigated the impacts of H3 lysine 4 trimethylation (H3K4me3) and specific histone methyltransferases of H3K4 methylation, su(var)3-9, enhancer-of-zeste, and trithorax domain 1A (SETD1A) on periodontal tissue affected by the diabetic condition. We observed the increase in H3K4me3 and SETD1A in gingival tissue of diabetic rats compared with the normal rats. Cultured human fibroblasts (hGFs) confirmed a high glucose-induced increase in H3K4me3 and SETD1A. We further demonstrated that high glucose increased the gene expression of matrix metalloproteinase (MMP) 1 and MMP13, which were canceled by sinefungin, an SETD1A inhibitor. Our investigation suggests that diabetes triggers histone modifications in the gingival tissue, resulting in gingival inflammation. Histone modifications may play crucial roles in the development of periodontal disease in diabetes.
A De Novo Splicing Mutation of STXBP1 in Epileptic Encephalopathy Associated with Hypomyelinating Leukodystrophy
Authors: Wang Zixuan , Zhang Jun , Zhou Yunfei , Liu Guicen , Tian Zixin , Song Xi
Published: October 2024

Deleterious variations in STXBP1 are responsible for early infantile epileptic encephalopathy type 4 (EIEE4, OMIM # 612164) because of its dysfunction in the central nervous system. The clinical spectrum of the neurodevelopmental delays associated with STXBP1 aberrations is collectively defined as STXBP1 encephalopathy (STXBP1-E), the conspicuous features of which are highlighted by early-onset epileptic seizures without structural brain anomalies. A girl was first diagnosed with unexplained disorders of movement and cognition, which later developed into STXBP1-E with unexpected leukoaraiosis and late onset of seizures. Genetic screening and molecular tests alongside neurological examinations were employed to investigate the genetic etiology and establish the diagnosis. A heterozygous mutation of c.37+2dupT at the STXBP1 splice site was identified as the pathogenic cause in the affected girl. The de novo mutation (DNM) did not result in any truncated proteins but immediately triggered mRNA degradation by nonsense-mediated mRNA decay (NMD), which led to the haploinsufficiency of STXBP1. The patient showed atypical phenotypes characterized by hypomyelinating leukodystrophy, and late onset of epileptic seizures, which had never previously been delineated in STXBP1-E. These findings strongly indicated that the haploinsufficiency of STXBP1 could also exhibit divergent clinical phenotypes because of the genetic heterogeneity in the subset of encephalopathies.
Genome-Wide Identification and Expression Analysis of the ALKB Homolog Gene Family in Potato (Solanum tuberosum L.)
Authors: Li Yan , Dong Xuanming , Ma Jianyu , Sui Chenxin , Jian Hongju , Lv Dianqiu
Published: October 2024

N6-methyladenosine (m6A) is an abundant and pervasive post-transcriptional modification in eukaryotic mRNAs. AlkB homolog (ALKBH) proteins play crucial roles in RNA metabolism and translation, participating in m6A methylation modification to regulate plant development. However, no comprehensive investigations have been conducted on ALKBH in potato. Here, 11 StALKBH family genes were identified in potato and renamed according to BLASTP and phylogenetic analyses following the Arabidopsis genome. The characteristics, sequence structures, motif compositions, phylogenetics, chromosomal locations, synteny, and promoter cis-acting element predictions were analyzed, revealing distinct evolutionary relationships between potato and other species (tomato and Arabidopsis). Homologous proteins were classified into seven groups depending on similar conserved domains, which implies that they possess a potentially comparable function. Moreover, the StALKBHs were ubiquitous, and their expression was examined in the various tissues of a whole potato, in which the StALKBH genes, except for StALKBH2, were most highly expressed in the stolon and flower. Multiple hormone and stress-response elements were found to be located in the promoters of the StALKBH genes. Further qRT-PCR results suggest that they may be significantly upregulated in response to phytohormones and abiotic stress (except for cold), and the expression of most of the StALKBH genes exhibited positively modulated trends. Overall, this study is the first to report a genome-wide assessment of the ALKBH family in potato, providing valuable insights into candidate gene selection and facilitating in-depth functional analyses of ALKBH-mediated m6A methylation mechanisms in potato.
Effects of Environmental Noise Stress on Mouse Metabolism
Authors: Lee Jungmin , Yang Jehoon , Kim Jeyun , Jang Yoonjung , Lee Jisun , Han Daehyun , Kim Hunnyun , Jeong Byong Chang , Seong Je Kyung
Published: October 2024

Environmental noise is associated with various health outcomes. However, the mechanisms through which these outcomes influence behavior and metabolism remain unclear. This study investigated how environmental noise affects the liver, adipose tissue, and brain metabolic functions, leading to behavioral and body weight changes. Mice were divided into a noise group exposed to construction noise and an unexposed (control) group. Behavior and body weight changes were monitored over 50 days. Early changes in response to noise exposure were assessed by measuring plasma cortisol and glial fibrillary acidic protein expression in brain tissues on days 1, 15, and 30. Chronic responses, including changes in lipoprotein and fat metabolism and neurotransmitters, were investigated by analyzing serum lipoprotein levels and body fat mass and evaluating liver, fat, and brain tissue after 50 days. The noise group showed higher locomotor activity and reduced anxiety in the open-field and Y-maze tests. Noise exposure caused an initial weight loss; however, chronic noise increased fat mass and induced adipocyte hypertrophy. Our findings underscore the role of environmental noise-induced stress in augmenting locomotor activity and reducing anxiety in mice through neurotransmitter modulation while increasing the risk of obesity by decreasing HDL cholesterol levels and promoting adipocyte hypertrophy.
Genomic Diversity of Streptomyces clavuligerus: Implications for Clavulanic Acid Biosynthesis and Industrial Hyperproduction
Authors: Ríos-Fernández Paula , Caicedo-Montoya Carlos , Ríos-Estepa Rigoberto
Published: October 2024

Streptomyces clavuligerus is a species used worldwide to industrially produce clavulanic acid (CA), a molecule that enhances antibiotic effectiveness against β-lactamase-producing bacterial strains. Despite its low inherent CA production, hyper-producing strains have been developed. However, genomic analyses specific to S. clavuligerus and CA biosynthesis are limited. Genomic variations that may influence CA yield were explored using S. clavuligerus strain genomes from diverse sources. Despite the slight differences obtained by similarity index calculation, pan-genome estimation revealed that only half of the genes identified were present in all strains. As expected, core genes were associated with primary metabolism, while the remaining genes were linked to secondary metabolism. Differences at the sequence level were more likely to be found in regions close to the tips of the linear chromosome. Wild-type strains preserved larger chromosomal and plasmid regions compared to industrial and/or hyper-producing strains; such a grouping pattern was also found through refined phylogenetic analyses. These results provide essential insights for the development of hyper-producing S. clavuligerus strains, attending to the critical demand for this antibiotic enhancer and contributing to future strategies for CA production optimization.
Identification of Phospholipids Relevant to Cancer Tissue Using Differential Ion Mobility Spectrometry
Authors: Sioris Patrik , Mäkelä Meri , Kontunen Anton , Karjalainen Markus , Vehkaoja Antti , Oksala Niku , Roine Antti
Published: October 2024

Phospholipids are the main building components of cell membranes and are also used for cell signaling and as energy storages. Cancer cells alter their lipid metabolism, which ultimately leads to an increase in phospholipids in cancer tissue. Surgical energy instruments use electrical or vibrational energy to heat tissues, which causes intra- and extracellular water to expand rapidly and degrade cell structures, bursting the cells, which causes the formation of a tissue aerosol or smoke depending on the amount of energy used. This gas phase analyte can then be analyzed via gas analysis methods. Differential mobility spectrometry (DMS) is a method that can be used to differentiate malignant tissue from benign tissues in real time via the analysis of surgical smoke produced by energy instruments. Previously, the DMS identification of cancer tissue was based on a ‘black box method’ by differentiating the 2D dispersion plots of samples. This study sets out to find datapoints from the DMS dispersion plots that represent relevant target molecules. We studied the ability of DMS to differentiate three subclasses of phospholipids (phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine) from a control sample using a bovine skeletal muscle matrix with a 5 mg addition of each phospholipid subclass to the sample matrix. We trained binary classifiers using linear discriminant analysis (LDA) and support vector machines (SVM) for sample classification. We were able to identify phosphatidylcholine, -inositol, and -ethanolamine with SVM binary classification accuracies of 91%, 73%, and 66% and with LDA binary classification accuracies of 82%, 74%, and 72%, respectively. Phosphatidylcholine was detected with a reliable classification accuracy, but ion separation setups should be adjusted in future studies to reliably detect other relevant phospholipids such as phosphatidylinositol and phosphatidylethanolamine and improve DMS as a microanalysis method and identify other phospholipids relevant to cancer tissue.
Therapeutic Effects of Proanthocyanidins on Diabetic Erectile Dysfunction in Rats
Authors: Zeng Xiaoyan , Li Lanlan , Tong Li
Published: October 2024

The rising occurrence of erectile dysfunction related to diabetes mellitus (DMED) has led to the creation of new medications. Proanthocyanidins (PROs) is a potential agent for DMED. In this study, the DMED rat model was established using streptozotocin (STZ) and erectile function was assessed using apomorphine (APO) in rats. Following this, the rats were subjected to oral treatment with PRO. Then, we evaluated the influence of PROs on DMED rats. The findings suggest that PROs significantly enhance erectile function in DMED rats. PROs modulated glucose and lipid metabolism in DMED rats by decreasing blood glucose and lipid levels while increasing liver glycogen and serum insulin levels. Furthermore, PROs enhanced vascular endothelial function in DMED rats by augmenting nitric oxide (NO) levels and reducing the levels of endothelin-1 (ET-1) and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). Additionally, PROs have been shown to elevate testosterone (T) levels, mitigate pathological testicular damage, and enhance sperm concentration and survival rates. Finally, the core targets were screened using network pharmacology, followed by validation through molecular docking, enzyme-linked immunoassay (ELISA), and real-time PCR methodologies. Our findings imply that PROs may treat DMED by elevating AKT1 levels while concurrently diminishing CASP3 levels, thereby effectively regulating the PI3K-Akt signaling pathway. Overall, these results support using PROs as a potential candidate for the treatment of DMED.
Reporter Alleles in hiPSCs: Visual Cues on Development and Disease
Authors: Cotta Gustavo Caldeira , Teixeira dos Santos Rachel Castro , Costa Guilherme Mattos Jardim , Lacerda Samyra Maria dos Santos Nassif
Published: October 2024

Reporter alleles are essential for advancing research with human induced pluripotent stem cells (hiPSCs), notably in developmental biology and disease modeling. This study investigates the state-of-the-art gene-editing techniques tailored for generating reporter alleles in hiPSCs, emphasizing their effectiveness in investigating cellular dynamics and disease mechanisms. Various methodologies, including the application of CRISPR/Cas9 technology, are discussed for accurately integrating reporter genes into the specific genomic loci. The synthesis of findings from the studies utilizing these reporter alleles reveals insights into developmental processes, genetic disorder modeling, and therapeutic screening, consolidating the existing knowledge. These hiPSC-derived models demonstrate remarkable versatility in replicating human diseases and evaluating drug efficacy, thereby accelerating translational research. Furthermore, this review addresses challenges and future directions in refining the reporter allele design and application to bolster their reliability and relevance in biomedical research. Overall, this investigation offers a comprehensive perspective on the methodologies, applications, and implications of reporter alleles in hiPSC-based studies, underscoring their essential role in advancing both fundamental scientific understanding and clinical practice.
The Role of Mast Cells in the Remodeling Effects of Molecular Hydrogen on the Lung Local Tissue Microenvironment under Simulated Pulmonary Hypertension
Authors: Atiakshin Dmitrii , Kostin Andrey , Alekhnovich Alexander , Volodkin Artem , Ignatyuk Michael , Klabukov Ilya , Baranovskii Denis , Buchwalow Igor , Tiemann Markus , Artemieva Marina , Medvedeva Nataliya , LeBaron Tyler W. , Noda Mami , Medvedev Oleg
Published: October 2024

Molecular hydrogen (H2) has antioxidant, anti-inflammatory, and anti-fibrotic effects. In a rat model simulating pulmonary fibrotic changes induced by monocrotaline-induced pulmonary hypertension (MPH), we had previously explored the impact of inhaled H2 on lung inflammation and blood pressure. In this study, we further focused the biological effects of H2 on mast cells (MCs) and the parameters of the fibrotic phenotype of the local tissue microenvironment. MPH resulted in a significantly increased number of MCs in both the pneumatic and respiratory parts of the lungs, an increased number of tryptase-positive MCs with increased expression of TGF-β, activated interaction with immunocompetent cells (macrophages and plasma cells) and fibroblasts, and increased MC colocalization with a fibrous component of the extracellular matrix of connective tissue. The alteration in the properties of the MC population occurred together with intensified collagen fibrillogenesis and an increase in the integral volume of collagen and elastic fibers of the extracellular matrix of the pulmonary connective tissue. The exposure of H2 together with monocrotaline (MCT), despite individual differences between animals, tended to decrease the intrapulmonary MC population and the severity of the fibrotic phenotype of the local tissue microenvironment compared to changes in animals exposed to the MCT effect alone. In addition, the activity of collagen fibrillogenesis associated with MCs and the expression of TGF-β and tryptase in MCs decreased, accompanied by a reduction in the absolute and relative content of reticular and elastic fibers in the lung stroma. Thus, with MCT exposure, inhaled H2 has antifibrotic effects involving MCs in the lungs of rats. This reveals the unknown development mechanisms of the biological effects of H2 on the remodeling features of the extracellular matrix under inflammatory background conditions of the tissue microenvironment.
Pyrimidine Derivatives as Selective COX-2 Inhibitors with Anti-Inflammatory and Antioxidant Properties
Authors: Tylińska Beata , Janicka-Kłos Anna , Gębarowski Tomasz , Nowotarska Paulina , Plińska Stanisława , Wiatrak Benita
Published: October 2024

Pyrimidine derivatives exhibit a wide range of biological activities, including anti-inflammatory properties. The aim of this study was to investigate the effects of tested pyrimidine derivatives on the activity of cyclooxygenase isoenzymes (COX-1 and COX-2), antioxidant properties, and their ability to inhibit the growth of inflammatory cells. In vitro tests were conducted to assess the ability of pyrimidine derivatives L1–L4 to inhibit COX-1 and COX-2 activity using the TMPD oxidation assay (N,N,N′,N′-tetramethyl-p-phenylenediamine). The compounds’ ability to inhibit the growth of lipopolysaccharide (LPS)-stimulated THP-1 (human leukemia monocytic) monocyte cells and their impact on reactive oxygen species (ROS) levels in an inflammatory model were also evaluated. The binding properties of human serum albumin (HSA) were assessed using UV–Vis spectroscopy, circular dichroism (CD), and isothermal titration calorimetry (ITC). Among the tested pyrimidine derivatives, L1 and L2 showed high selectivity towards COX-2, outperforming piroxicam and achieving results comparable to meloxicam. In the sulforhodamine B (SRB) assay, L1 and L2 demonstrated dose-dependent inhibition of LPS-stimulated THP-1 cell growth. Additionally, ROS assays indicated that these compounds reduced free radical levels, confirming their antioxidant properties. Binding studies with albumin revealed that L1 and L2 formed stable complexes with HSA. These results suggest that these compounds could serve as a basis for further research into anti-inflammatory and anticancer drugs with reduced toxicity.
Comparative Transcriptomic Analysis Reveals Domestication and Improvement Patterns of Broomcorn Millet (Panicum miliaceum L.)
Authors: Zhao Xinyu , Liu Minxuan , Li Chunxiang , Zhang Jingyi , Li Tianshu , Sun Fengjie , Lu Ping , Xu Yue
Published: October 2024

Broomcorn millet (Panicum miliaceum L.) is one of the earliest crops, domesticated nearly 8000 years ago in northern China. It gradually spread across the entire Eurasian continent, as well as to America and Africa, with recent improvement in various reproductive and vegetative traits. To identify the genes that were selected during the domestication and improvement processes, we performed a comparative transcriptome analysis based on wild types, landraces, and improved cultivars of broomcorn millet at both seeding and filling stages. The variations in gene expression patterns between wild types and landraces and between landraces and improved cultivars were further evaluated to explore the molecular mechanisms underlying the domestication and improvement of broomcorn millet. A total of 2155 and 3033 candidate genes involved in domestication and a total of 84 and 180 candidate genes related to improvement were identified at seedling and filling stages of broomcorn millet, respectively. The annotation results suggested that the genes related to metabolites, stress resistance, and plant hormones were widely selected during both domestication and improvement processes, while some genes were exclusively selected in either domestication or improvement stages, with higher selection pressure detected in the domestication process. Furthermore, some domestication- and improvement-related genes involved in stress resistance either lost their functions or reduced their expression levels due to the trade-offs between stress resistance and productivity. This study provided novel genetic materials for further molecular breeding of broomcorn millet varieties with improved agronomic traits.
Research on the Action and Mechanism of Pharmacological Components of Omphalia lapidescens
Authors: Xu Keyang , Wang Li , He Dan
Published: October 2024

Omphalia lapidescens is a macrofungus that is used in traditional Chinese medicine for its insecticidal and stagnation-relieving properties. The active ingredients of this fungus including proteins, polysaccharides and sterols have been demonstrated to exhibit antiparasitic, anti-inflammatory, and antitumor effects. Omphalia has been used in clinical cancer treatment. Many studies on Omphalia have concentrated on its cytotoxicity and anticancer effects. However, the investigation of its natural metabolites remains a significant area for further research. This review presents a comprehensive analysis of the research progress concerning the pharmacological components of Omphalia. The aim of this discussion is to provide a reference for further in-depth study of Omphalia, with the objective of exploring its potential value. Therefore, the focus of this review was on the classification of metabolites in Omphalia and their mechanisms of action.