bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of key miRNAs and target genes in extracellular vesicles derived from low-intensity pulsed ultrasound-treated stem cells
Authors: Yin Xin , Yi Jialian , Mao Fugang , Tang Qisheng , Zhang Xinyu , Yang Xiaoyu , Xie Hongqing , Wang Linping , Sun Shuifen , Yu Xin , Liu Jie , Jiang Lihong 
Published: January 2025

ObjectivesThis study aimed to investigate the impact of low-intensity pulsed ultrasound (LIPUS) treatment on the miRNA and mRNA profiles of stem cell-derived extracellular vesicles (EVs). Specifically, it sought to identify key miRNAs and their target mRNAs associated with enhanced therapeutic efficacy in LIPUS-treated stem cell-derived EVs.MethodsUtilizing miRNA deep-sequencing data from the Gene Expression Omnibus database, differential gene analysis was performed. MiRNA-mRNA target analysis, functional and pathway enrichment analysis, protein-protein interaction network construction, and hub gene identification were conducted. Validation of differentially expressed miRNAs was performed via RT-qPCR in human umbilical cord mesenchymal stem cells (hUC-MSCs) treated with LIPUS.ResultsTen differentially expressed miRNAs were identified, with six upregulated and four downregulated miRNAs in LIPUS-treated stem cell-derived EVs. Functional enrichment analysis revealed involvement in biological processes such as regulation of metabolic processes, cellular component organization, and response to stress, as well as signaling pathways like cell cycle, MAPK signaling, and Hippo signaling. Protein-protein interaction network analysis identified key hub genes including MYC, GAPDH, HSP90AA1, EP300, JUN, PTEN, DAC1, STAT3, HSPA8, and HIF1A associated with LIPUS treatment. RT-qPCR validation confirmed differential expression of selected miRNAs (hsa-miR-933, hsa-miR-3943, hsa-miR-4633-5p, hsa-miR-592, hsa-miR-659-5p, hsa-miR-4766-3p) in LIPUS-treated hUC-MSCs.ConclusionThis study sheds light on the potential therapeutic mechanisms underlying LIPUS-treated stem cell-derived EVs. The identified differentially expressed miRNAs and their potential target mRNAs offer valuable insights into the biological processes influenced by LIPUS treatment. While further investigation is necessary to validate their roles as therapeutic targets, this study lays the groundwork for future research on optimizing SC-EV therapy with LIPUS preconditioning.
Difference between estimated glomerular filtration rate based on cystatin C versus creatinine and cardiovascular–kidney–metabolic health
Authors: Wu Xiaoyan , Hu Wuming , Xu Jian , Shen Jiayi , Lin Li , Zhu Jingshuai , Wei Tiemin , Lv Lingchun 
Published: January 2025

BackgroundThe difference between the estimated glomerular filtration rate (eGFR) calculated from cystatin C and creatinine (eGFRdiff) serves as a biomarker of kidney function impairment. However, the role of eGFRdiff in cardiovascular–kidney–metabolic (CKM) health and its impact on mortality in CKM syndrome patients has not yet been studied.MethodsThis study included 3,622 participants from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2004. Weighted ordinal logistic regression was used to explore the link between eGFRdiff and CKM health, while weighted Cox regression was used to examine the relationship between eGFRdiff and mortality in CKM syndrome patients. Restricted cubic splines (RCSs) were used to analyze the dose–response relationship.ResultsThe common odds ratio (cOR) per 10 mL/min/1.73m2 increase in eGFRdiff was 0.86 [95% confidence interval (CI), 0.81 to 0.91]. Compared to the midrange eGFRdiff, the cOR values for the negative and positive eGFRdiff were 1.88 [95% CI, 1.23 to 2.88] and 0.69 [95% CI, 0.58 to 0.83], respectively. During a median follow-up of 201 months, 853 participants died from all causes, while 265 died due to cardiovascular causes. The hazard ratios (HRs) per 10 mL/min/1.73m2 increase in eGFRdiff were 0.88 [95% CI, 0.83 to 0.93] for all-cause mortality and 0.90 [95% CI, 0.81 to 1.00] for cardiovascular mortality cases. Compared to the participants with a midrange eGFRdiff, those with negative eGFRdiff had a 48% higher risk of all-cause mortality, while those with positive eGFRdiff had a 30% lower risk. No significant non-linear associations were found in these regression analyses.ConclusionOur study found that eGFRdiff is associated with CKM health and stratified mortality risk in CKM syndrome patients.
Association between self-reported eye conditions in patients at rural federally qualified health centers and vision-targeted health-related quality of life: the AL-SIGHT study
Authors: Swain Thomas A. , McGwin Gerald , Rhodes Lindsay A. , Girkin Christopher A. , Owsley Cynthia 
Published: January 2025

BackgroundFederally Qualified Health Centers (FQHCs) are safety-net primary health care clinics in the US serving medically underserved areas and populations. We administered the National Eye Institute Visual Function Questionnaire – 9 (VFQ-9), a vision-targeted, health-related quality of life questionnaire, to patients in 3 FQHCs in rural Alabama at risk for glaucoma. We examined demographic factors and self-reported eye conditions associated with VFQ-9 scores.MethodsThe VFQ-9 (score range 0–100) was administered to patients at-risk for glaucoma including African Americans or Hispanics ≥40 years, white persons ≥50 years, persons with diabetes ≥18 years, ≥18 years with glaucoma or glaucoma suspect, and/or ≥ 18 years with a family history of glaucoma. Demographic variables were collected -- age, gender, race/ethnicity, employment, marital status, health insurance, education, and driving status. Patients reported the presence of eye conditions including glaucoma and many other eye conditions. Stepwise linear regression modeled which variables accounted for the greatest variance of the VFQ-9 score.ResultsComposite VFQ-9 scores averaged 82.4. The best fitting model for VFQ-9 scores included being a driver, insurance type/status, self-reported glaucoma or glaucoma suspect, blurry vision, and double vision.ConclusionPatients at-risk for glaucoma seeking care at FQHCs in rural Alabama have moderate impairment in quality of life as assessed by the VFQ-9. Factors negatively influencing scores are self-reported glaucoma or glaucoma suspect, blurry vision, double vision, not being a driver, and having no health insurance. The VFQ-9 is a good candidate as a vision-targeted quality of life outcome for eye health interventions at rural FQHCs in those with glaucoma.
Angelica sinensis polysaccharide as potential protectants against recurrent spontaneous abortion: focus on autophagy regulation
Authors: Sun Yeli , Li Guohua , Kong Mengwen , Li Junyuan , Wang Shuyun , Tan Yuan 
Published: January 2025

IntroductionRecurrent spontaneous abortion (RSA) represents a significant clinical challenge, with its underlying mechanisms yet to be fully elucidated. Despite advances in understanding, the precise pathophysiology driving RSA remains unclear. Angelica sinensis, a traditional herbal remedy, is frequently used as an adjunctive treatment for miscarriage. However, it remains uncertain whether its primary active component, Angelica sinensis polysaccharide (ASP), plays a definitive role in its therapeutic effects. The specific function and mechanism of ASP in the context of RSA require further investigation.MethodsIn this study, we sought to evaluate autophagy levels at the maternal-fetal interface in RSA patients and in an RSA mouse model treated with ASP, complemented by a comprehensive metabolomic analysis. Autophagy flux in the decidua was compared between eight RSA patients and eight healthy pregnant women. Additionally, changes in autophagy flux were assessed in an RSA mouse model following ASP treatment, with embryos and placental tissues collected for subsequent metabolomic profiling.ResultsOur results revealed a significant reduction in Beclin 1 protein levels in the decidua of RSA patients compared to the normal pregnancy group. Conversely, ASP treatment in the RSA mouse model restored autophagy-related protein expression, including ATG7, ATG16L, and Beclin 1, to levels higher than those observed in the untreated RSA group. Metabolomic analyses further identified significant changes in phosphatidylethanolamine levels between ASP-treated and control groups, with differential metabolites enriched in pathways related to glycolysis/gluconeogenesis, glycerolipid metabolism, and glycine, serine, and threonine metabolism. Functional assays revealed that ASP enhances trophoblast cell proliferation, migration, and invasion.ConclusionIn summary, our findings demonstrate diminished autophagy activity in RSA patients, while ASP appears to restore autophagy and regulate key metabolic pathways, including glycolysis/gluconeogenesis. These results provide new insights into the protective mechanisms of ASP in RSA, suggesting its potential as a therapeutic intervention for this condition.
Acute stress triggers sex-dependent rapid alterations in the human small intestine microbiota composition
Authors: Rodiño-Janeiro Bruno K. , Khannous-Lleiffe Olfat , Pigrau Marc , Willis Jesse R. , Salvo-Romero Eloísa , Nieto Adoración , Expósito Elba , Fortea Marina , Pardo-Camacho Cristina , Albert-Bayo Mercé , González-Castro Ana María , Guagnozzi Danila , Martínez Cristina , Lobo Beatriz , Vicario María , Santos Javier , Gabaldón Toni , Alonso-Cotoner Carmen 
Published: January 2025

Background/aimsDigestive disorders of gut-brain interaction (DGBI) are very common, predominant in females, and usually associated with intestinal barrier dysfunction, dysbiosis, and stress. We previously found that females have increased susceptibility to intestinal barrier dysfunction in response to acute stress. However, whether this is associated with changes in the small bowel microbiota remains unknown. We have evaluated changes in the small intestinal microbiota in response to acute stress to better understand stress-induced intestinal barrier dysfunction.MethodsJejunal biopsies were obtained at baseline and 90 min after cold pain or sham stress. Autonomic (blood pressure and heart rate), hormonal (plasma cortisol and adrenocorticotropic hormone) and psychological (Subjective Stress Rating Scale) responses to cold pain and sham stress were monitored. Microbial DNA from the biopsies was analyzed using a 16S metabarcoding approach before and after cold pain stress and sham stress. Differences in diversity and relative abundance of microbial taxa were examined.ResultsCold pain stress was associated with a significant decrease in alpha diversity (P = 0.015), which was more pronounced in females, along with significant sex differences in the abundance of specific taxa and the overall microbiota composition. Microbiota alterations significantly correlated with changes in psychological responses, hormones, and gene expression in the intestinal mucosal. Cold pain stress was also associated with activation of autonomic, hormonal and psychological response, with no differences between sexes.ConclusionsAcute stress elicits rapid alterations in bacterial composition in the jejunum of healthy subjects and these changes are more pronounced in females. Our results may contribute to the understanding of female predominance in DGBI.
Resistance to medically important antimicrobials in broiler and layer farms in Cameroon and its relation with biosecurity and antimicrobial use
Authors: Vougat Ngom Ronald , Laconi Andrea , Tolosi Roberta , Akoussa Adonis M. M. , Ziebe Stephane D. , Kouyabe Vincent M. , Piccirillo Alessandra 
Published: January 2025

IntroductionPoultry production accounts for 42% of Cameroonian meat production. However, infectious diseases represent the main hindrance in this sector, resulting in overuse and misuse of antimicrobials that can contribute to the emergence and dissemination of antimicrobial resistance (AMR). This study aimed to evaluate the prevalence of antimicrobial resistance genes (ARGs) conferring resistance to carbapenems (blaVIM-2 and blaNDM), (fluoro) quinolones (qnrS, qnrA, and qnrB), polymyxins (mcr1 to mcr5), and macrolides (ermA and ermB) in the poultry farm environment. Additionally, the study examined the relationship between these ARGs and biosecurity implementation, as well as farmers’ knowledge, attitudes, and practices toward antimicrobial use (AMU) and AMR, including their perception of AMR risk.Materials and methodsFecal, drinking water, and biofilm samples from drinking water pipelines were collected from 15 poultry farms and subsequently analyzed by real-time PCR and 16S rRNA NGS.ResultsAll samples tested positive for genes conferring resistance to (fluoro) quinolones, 97.8% to macrolides, 64.4% to polymyxins, and 11.1% to carbapenems. Of concern, more than half of the samples (64.4%) showed a multi-drug resistance (MDR) pattern (i.e., resistance to ≥3 antimicrobial classes). Drinking water and biofilm microbial communities significantly differed from the one of the fecal samples, both in term of diversity (α-diversity) and composition (β-diversity). Furthermore, opportunistic pathogens (i.e., Comamonadaceae and Sphingomonadaceae) were among the most abundant bacteria in drinking water and biofilm. The level of biosecurity implementation was intermediate, while the knowledge and attitude of poultry farmers toward AMU were insufficient and unsuitable, respectively. Good practices toward AMU were found to be correlated with a reduction in polymyxins and MDR.DiscussionThis study provides valuable information on resistance to medically important antimicrobials in poultry production in Cameroon and highlights their potential impact on human and environmental health.
Predicting patient outcomes with gene-expression biomarkers from colorectal cancer organoids and cell lines
Authors: Razumovskaya Alexandra , Silkina Mariia , Poloznikov Andrey , Kulagin Timur , Raigorodskaya Maria , Gorban Nina , Kudryavtseva Anna , Fedorova Maria , Alekseev Boris , Tonevitsky Alexander , Nikulin Sergey 
Published: January 2025

IntroductionColorectal cancer (CRC) is characterized by an extremely high mortality rate, mainly caused by the high metastatic potential of this type of cancer. To date, chemotherapy remains the backbone of the treatment of metastatic colorectal cancer. Three main chemotherapeutic drugs used for the treatment of metastatic colorectal cancer are 5-fluorouracil, oxaliplatin and irinotecan which is metabolized to an active compound SN-38. The main goal of this study was to find the genes connected to the resistance to the aforementioned drugs and to construct a predictive gene expression-based classifier to separate responders and non-responders.MethodsIn this study, we analyzed gene expression profiles of seven patient-derived CRC organoids and performed correlation analyses between gene expression and IC50 values for the three standard-of-care chemotherapeutic drugs. We also included in the study publicly available datasets of colorectal cancer cell lines, thus combining two different in vitro models relevant to cancer research. Logistic regression was used to build gene expression-based classifiers for metastatic Stage IV and non-metastatic Stage II/III CRC patients. Prognostic performance was evaluated through Kaplan-Meier survival analysis and log-rank tests, while independent prognostic significance was assessed using multivariate Cox proportional hazards modeling.ResultsA small set of genes showed consistent correlation with resistance to chemotherapy across different datasets. While some genes were previously implicated in cancer prognosis and drug response, several were linked to drug resistance for the first time. The resulting gene expression signatures successfully stratified Stage II/III and Stage IV CRC patients, with potential clinical utility for improving treatment outcomes after further validation.DiscussionThis study highlights the advantages of integrating diverse experimental models, such as organoids and cell lines, to identify novel prognostic biomarkers and enhance the understanding of chemotherapy resistance in CRC.
Cognitive trajectories and their relationships with education and diets among older adults: a network-based 10-year cohort study
Authors: Wang Xuchun , Qiao Yuchao , Zhang Yudong , Cui Yu , Ren Hao , Hao Chongqi , Qiu Lixia 
Published: January 2025

ObjectivesFew studies have examined the underlying mechanisms of education, diets, and cognitive function in older adults. This study analyses the relationship between cognitive trajectories, education, and different dietary patterns in older adults from a network perspective, and further explores their longitudinal associations and mediation effects.MethodsData on cognitive trajectories were derived from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) between 2008 and 2018. Group-Based Trajectory Model (GBTM) was used to identify potential heterogeneity in the longitudinal changes in cognitive function. Multinomial logistic regression and network analysis were then applied to examine the relationships between different cognitive trajectories and years of education, food variety (FV), and plant-based dietary patterns. Cross-lagged panel model was used to examine the longitudinal associations between education, FV, and plant-based diet patterns. Furthermore, we constructed a mediation model based on categorical variables for cognitive trajectories to investigate the mediating effect of FV and plant-based diet index on education and cognitive.ResultsA total of 2,115 older adults were included in this study, revealing three distinct cognitive function trajectories. After controlling for potential confounders, education and dietary-related variables were associated with a cognitive stable decline trajectory (OR: 0.857/0.929/1.027) and a cognitive rapid decline trajectory (OR: 0.859/0.914, 95% CI: 0.775–0.882) compared to the cognitive stable trajectory. In the education, diet, and cognition network model, overall Plant-Based Diet Index (PDI) [expected influence (EI) = 1.82] and years of education (EI = 0.54) were the most central domains. There were longitudinal associations between education, FV, and plant-based dietary patterns, which were significant only in the slow decline group. FV acting as a mediator between education and cognitive trajectories.ConclusionYears of education are longitudinally associated with the diet of older adults in the slow cognitive decline group. Food diversity partially mediates the relationship between years of education and cognitive trajectories. Interventions targeting education and dietary behaviors may help alleviate cognitive decline in older adults.
The global research of magnetic resonance imaging in Alzheimer’s disease: a bibliometric analysis from 2004 to 2023
Authors: Sun Xiaoyu , Zhu Jianghua , Li Ruowei , Peng Yun , Gong Lianggeng 
Published: January 2025

BackgroundAlzheimer’s disease (AD) is a common neurodegenerative disorder worldwide and the using of magnetic resonance imaging (MRI) in the management of AD is increasing. The present study aims to summarize MRI in AD researches via bibliometric analysis and predict future research hotspots.MethodsWe searched for records related to MRI studies in AD patients from 2004 to 2023 in the Web of Science Core Collection (WoSCC) database. CiteSpace was applied to analyze institutions, references and keywords. VOSviewer was used for the analysis of countries, authors and journals.ResultsA total of 13,659 articles were obtained in this study. The number of published articles showed overall exponential growth from 2004 to 2023. The top country and institution were the United States and the University of California System, accounting for 40.30% and 9.88% of the total studies, respectively. Jack CR from the United States was the most productive author. The most productive journal was the Journal of Alzheimers Disease. Keyword burst analysis revealed that “machine learning” and “deep learning” were the keywords that frequently appeared in the past 6 years. Timeline views of the references revealed that “#0 tau pathology” and “#1 deep learning” are currently the latest research focuses.ConclusionThis study provides an in-depth overview of publications on MRI studies in AD. The United States is the leading country in this field with a concentration of highly productive researchers and high-level institutions. The current research hotspot is deep learning, which is being applied to develop noninvasive diagnosis and safer treatment of AD.
Uncovering novel KCC2 regulatory motifs through a comprehensive transposon-based mutant library
Authors: Uvarov Pavel , Fudo Satoshi , Karakus Cem , Golubtsov Andrey , Rotondo Federico , Sukhanova Tatiana , Soni Shetal , Di Scala Coralie , Kajander Tommi , Rivera Claudio , Ludwig Anastasia 
Published: January 2025

IntroductionThe neuron-specific K-Cl cotransporter KCC2 maintains low intracellular chloride levels, which are crucial for fast GABAergic and glycinergic neurotransmission. KCC2 also plays a pivotal role in the development of excitatory glutamatergic neurotransmission by promoting dendritic spine maturation. The cytoplasmic C-terminal domain (KCC2-CTD) plays a critical regulatory role in the molecular mechanisms controlling the cotransporter activity through dimerization, phosphorylation, and protein interaction.MethodsTo identify novel CTD regulatory motifs, we used the Mu transposon-based mutagenesis system to generate a library of KCC2 mutants with 5 amino acid insertions randomly distributed within the KCC2-CTD. We determined the insertion positions in 288 mutants by restriction analysis and selected clones with a single insertion site outside known KCC2 regulatory motifs. We analyzed the subcellular distribution of KCC2-CTD mutants in cultured cortical neurons using immunocytochemistry and selected ten mutants with ectopic expression patterns for detailed characterization.ResultsA fluorescent Cl−-transport assay in HEK293 cells revealed mutants with both reduced and enhanced Cl−-extrusion activity, which overall correlated with their glycosylation patterns. Live-cell immunostaining analysis of plasma membrane expression of KCC2-CTD mutants in cultured cortical neurons corroborated the glycosylation data. Furthermore, the somatodendritic chloride gradient in neurons transfected with the KCC2-CTD mutants correlated with their Cl−-extrusion activity in HEK293 cells. Gain- and loss-of-function mutant positions were analyzed using available KCC2 cryo-EM structures.DiscussionTwo groups of mutants were identified based on 3D structural analysis. The first group, located near the interface of transmembrane and cytoplasmic domains, may affect interactions with the N-terminal inhibitory peptide regulating KCC2 activity. The second group, situated on the external surface of the cytoplasmic domain, may disrupt interactions with regulatory proteins. Analyzing CTD mutations that modulate KCC2 activity enhances our understanding of its function and is essential for developing novel anti-seizure therapies.