bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ezetimibe, Niemann-Pick C1 like 1 inhibitor, modulates hepatic phospholipid metabolism to alleviate fat accumulation
Authors: Yang Hyekyung , Suh Dong Ho , Jung Eun Sung , Lee Yoonjin , Liu Kwang-Hyeon , Do In-Gu , Lee Choong Hwan , Park Cheol-Young 
Published: June 2024

BackgroundEzetimibe, which lowers cholesterol by blocking the intestinal cholesterol transporter Niemann-Pick C1 like 1, is reported to reduce hepatic steatosis in humans and animals. Here, we demonstrate the changes in hepatic metabolites and lipids and explain the underlying mechanism of ezetimibe in hepatic steatosis.MethodsWe fed Otsuka Long-Evans Tokushima Fatty (OLETF) rats a high-fat diet (60 kcal % fat) with or vehicle (control) or ezetimibe (10 mg kg-1) via stomach gavage for 12 weeks and performed comprehensive metabolomic and lipidomic profiling of liver tissue. We used rat liver tissues, HepG2 hepatoma cell lines, and siRNA to explore the underlying mechanism.ResultsIn OLETF rats on a high-fat diet, ezetimibe showed improvements in metabolic parameters and reduction in hepatic fat accumulation. The comprehensive metabolomic and lipidomic profiling revealed significant changes in phospholipids, particularly phosphatidylcholines (PC), and alterations in the fatty acyl-chain composition in hepatic PCs. Further analyses involving gene expression and triglyceride assessments in rat liver tissues, HepG2 hepatoma cell lines, and siRNA experiments unveiled that ezetimibe’s mechanism involves the upregulation of key phospholipid biosynthesis genes, CTP:phosphocholine cytidylyltransferase alpha and phosphatidylethanolamine N-methyl-transferase, and the phospholipid remodeling gene lysophosphatidylcholine acyltransferase 3.ConclusionThis study demonstrate that ezetimibe improves metabolic parameters and reduces hepatic fat accumulation by influencing the composition and levels of phospholipids, specifically phosphatidylcholines, and by upregulating genes related to phospholipid biosynthesis and remodeling. These findings provide valuable insights into the molecular pathways through which ezetimibe mitigates hepatic fat accumulation, emphasizing the role of phospholipid metabolism.
Association of thrombocytopenia with immune checkpoint inhibitors: a large-scale pharmacovigilance analysis based on the data from FDA adverse event reporting system database
Authors: Liu Geliang , Zhang Shuxian , Mo Zhuang , Huang Tai , Yu Qi , Lu Xuechun , He Peifeng 
Published: June 2024

Introduction: An increasing number of immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) have been reported during clinical treatment. We aimed to explore the clinical characteristics of patients with ICIs-induced ITP under different therapeutic strategies based on the FAERS database and explore the potential biological mechanisms in combination with TCGA pan-cancer data.Methods: Data from FAERS were collected for ICIs adverse reactions between January 2012 and December 2022. Disproportionality analysis identified ICIs-induced ITP in the FAERS database using the reporting odds ratio (ROR), proportional reporting ratio (PRP), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker algorithms (MGPS). The potential biological mechanisms underlying ITP induced by ICIs were examined using TCGA transcriptome data on cancers.Results: In the FAERS, 345 ICIs-induced ITP reports were retrieved, wherein 290 (84.06%) and 55 (15.94%) were reported as monotherapy and combination therapy, respectively. The median age of the reported patients with ICIs-induced ITP was 69 years (IQR 60-76), of which 62 (18%) died and 47 (13.6%) had a life-threatening outcome. The majority of reported indications were lung, skin, and bladder cancers, and the median time to ITP after dosing was 42 days (IQR 17-135), with 64 patients (43.5%) experiencing ITP within 30 days of dosing and 88 patients experiencing ITP in less than 2 months (59.9%). The occurrence of ICIs-induced ITP may be associated with ICIs-induced dysregulation of the mTORC1 signaling pathway and megakaryocyte dysfunction.Conclusion: There were significant reporting signals for ITP with nivolumab, pembrolizumab, cemiplimab, atezolizumab, avelumab, durvalumab, ipilimumab, nivolumab/ipilimumab, and pembrolizumab/ipilimumab. Patients treated with anti-PD-1 in combination with anti-CTLA-4 are more likely to have an increased risk of ICIs-induced ITP. Patients with melanoma are at a higher risk of developing ITP when treated with ICI and should be closely monitored for this risk within 60 days of treatment. The potential biological mechanism of ICIs-induced ITP may be related to the dysfunction of megakaryocyte autophagy through the overactivation of the mTOR-related signaling pathway. This study provides a comprehensive understanding of ICIs-induced ITP. Clinicians should pay attention to this potentially fatal adverse reaction.
Staphylococcus arlettae mediated defense mechanisms and metabolite modulation against arsenic stress in Helianthus annuus
Authors: Qadir Muhammad , Hussain Anwar , Shah Mohib , Hamayun Muhammad , Iqbal Amjad , Irshad Muhammad , Ahmad Ayaz , Alrefaei Abdulwahed Fahad , Ali Sajid 
Published: June 2024

IntroductionArsenate, a metalloid, acting as an analog to phosphate, has a tendency to accumulate more readily in plant species, leading to adverse effects.MethodsIn the current study, sunflower seedlings were exposed to 25, 50 and 100 ppm of the arsenic.ResultsLikewise, a notable reduction (p&lt;0.05) was observed in the relative growth rate (RGR) by 4-folds and net assimilation rate (NAR) by 75% of Helianthus annuus when subjected to arsenic (As) stress. Nevertheless, the presence of Staphylococcus arlettae, a plant growth-promoting rhizobacterium with As tolerance, yielded an escalation in the growth of H. annuus within As-contaminated media. S. arlettae facilitated the conversion of As into a form accessible to plants, thereby, increasing its uptake and subsequent accumulation in plant tissues. S. arlettae encouraged the enzymatic antioxidant systems (Superoxide dismutase (SOD), peroxidase (POD), ascorbate peroxidase (APX) and catalase (CAT)) and non-enzymatic antioxidants (flavonoids, phenolics, and glutathione) in H. annuus seedlings following substantial As accumulation. The strain also induced the host plant to produce osmolytes like proline and sugars, mitigating water loss and maintaining cellular osmotic balance under As-induced stress. S. arlettae rectified imbalances in lignin content, reduced high malonaldehyde (MDA) levels, and minimized electrolyte leakage, thus counteracting the toxic impacts of the metal.ConclusionThe strain exhibited the capability to concurrently encourage plant growth and remediate Ascontaminated growth media through 2-folds rate of biotransformation and bio-mobilization.
Trends in genitourinary cancer mortality in the United States: analysis of the CDC-WONDER database 1999–2020
Authors: Ghazwani Yahia , Alghafees Mohammad , Suheb Mahammed Khan , Shafqat Areez , Sabbah Belal Nedal , Arabi Tarek Ziad , Razak Adhil , Sabbah Ahmad Nedal , Alaswad Marwan , AlKattan Wael , Ouban Abderrahman , Abdul Rab Saleha , Shawwaf Kenan Abdulhamid , AlKhamees Mohammad , Alasker Ahmed , Al-Khayal Abdullah , Alsaikhan Bader , Addar Abdulmalik , Aldosari Lama , Al Qurashi Abdullah A. , Musalli Ziyad 
Published: June 2024

IntroductionSociodemographic disparities in genitourinary cancer-related mortality have been insufficiently studied, particularly across multiple cancer types. This study aimed to investigate gender, racial, and geographic disparities in mortality rates for the most common genitourinary cancers in the United States.MethodsMortality data for prostate, bladder, kidney, and testicular cancers were obtained from the Centers for Disease Control and Prevention (CDC) WONDER database between 1999 and 2020. Age-adjusted mortality rates (AAMRs) were analyzed by year, gender, race, urban–rural status, and geographic region using a significance level of p &lt; 0.05.ResultsOverall, AAMRs for prostate, bladder, and kidney cancer declined significantly, while testicular cancer-related mortality remained stable. Bladder and kidney cancer AAMRs were 3–4 times higher in males than females. Prostate cancer mortality was highest in black individuals/African Americans and began increasing after 2015. Bladder cancer mortality decreased significantly in White individuals, Black individuals, African Americans, and Asians/Pacific Islanders but remained stable in American Indian/Alaska Natives. Kidney cancer-related mortality was highest in White individuals but declined significantly in other races. Testicular cancer mortality increased significantly in White individuals but remained stable in Black individuals and African Americans. Genitourinary cancer mortality decreased in metropolitan areas but either increased (bladder and testicular cancer) or remained stable (kidney cancer) in non-metropolitan areas. Prostate and kidney cancer mortality was highest in the Midwest, bladder cancer in the South, and testicular cancer in the West.DiscussionSignificant sociodemographic disparities exist in the mortality trends of genitourinary cancers in the United States. These findings highlight the need for targeted interventions and further research to address these disparities and improve outcomes for all populations affected by genitourinary cancers.
Research on the correlation between clinical nurses’ self-efficacy, future time perspective, and occupational burnout
Authors: Xie Daixun , Zhu Xiaoqin , Zhang Xiurong , Jiang Zhaoquan , Wang Xin , Liu Tao 
Published: June 2024

BackgroundThe number of clinical nurses in China experiencing professional burnout is increasing yearly, posing a serious challenge to the public health sector. Implementing effective intervention strategies is key to reducing the level of occupational burnout. At present, training aimed at alleviating occupational burnout among clinical nurses is very limited, with common training programs focusing on addressing external factors of occupational burnout rather than the internal cognitive issues of clinical nurses. Self-efficacy and future time perspective are both aspects of an individual’s internal self-cognition. Meanwhile, the relationship between clinical nurses’ self-efficacy, future time perspective, and occupational burnout is not clear, and further research is needed to verify this.ObjectiveThis study aims to reveal the relationship between clinical nurses’ self-efficacy, future time perspective, and occupational burnout, and to explore the mediating role of future time perspective between self-efficacy and occupational burnout among clinical nurses, providing a scientific reference for training directions to improve occupational burnout.MethodsThis study used a cross-sectional design, conducting a questionnaire survey with 529 practicing clinical nurses using the General Demographics Questionnaire (GDQ), the General Self-Efficacy Scale (GSES), the Zimbardo Time Perspective Inventory (ZTPI), and the Maslach Burnout Inventory-General Survey (MBI-GS). SPSS software version 26.0 was used to analyze the correlation between variables, and AMOS 26.0 was used to test the mediation effect.ResultsClinical nurses’ self-efficacy had a negative predictive effect on occupational burnout (r = −0.503, p &lt; 0.001). Future time perspective showed significant differences in regression coefficients on both the paths of self-efficacy (r = 0.615, p &lt; 0.001) and occupational burnout (r = −0.374, p &lt; 0.001). Future time perspective played a partial mediating role between self-efficacy and occupational burnout, accounting for 33.8% of the total effect.ConclusionThis study suggests a significant correlation between clinical nurses’ self-efficacy, future time perspective, and occupational burnout. Self-efficacy can directly affect occupational burnout in clinical nurses and can also indirectly affect occupational burnout through the future time perspective.
Association of diet and outdoor time with inflammatory bowel disease: a multicenter case-control study using propensity matching analysis in China
Authors: Chu Xiaotian , Chen Xuanfu , Zhang Huimin , Wang Yufang , Guo Hong , Chen Yan , Liu Xiaowei , Zhu Zhenhua , He Yao , Ding Xueli , Wang Qunying , Zheng Changqing , Cao Xiaocang , Yang Hong , Qian Jiaming 
Published: June 2024

ObjectiveTo investigate the association between dietary and some other environmental factors and the risk of inflammatory bowel diseases (IBD) in Chinese population.Materials and methodsA multicenter case-control study was conducted involving 11 hospitals across China. A total of 1,230 subjects were enrolled consecutively, and diet and environmental factor questionnaires were collected. IBD patients were matched with healthy controls (HC) using propensity-score matching (PSM) at a 1:1 ratio with a caliper value of 0.02. Multivariate conditional logistic regression analyses were performed to evaluate the associations between diet, environmental factors, and IBD.ResultsModerate alcohol and milk consumption, as well as daily intake of fresh fruit, were protective factors for both Crohn's disease (CD) and ulcerative colitis (UC). Conversely, the consumption of eggs and chocolate increased the risk of IBD. Outdoor time for more than 25% of the day was a protective factor only for CD. In eastern regions of China, CD patients had higher egg consumption and less outdoor time, while UC patients consumed more chocolate. IBD patients from urban areas or with higher per capita monthly income consumed more fruit, eggs, and chocolate.ConclusionsThis study reveals an association between specific foods, outdoor time, and the emergence of IBD in the Chinese population. The findings emphasize the importance of a balanced diet, sufficient outdoor time and activities, and tailored prevention strategies considering regional variations.
Evaluation of viability, developmental competence, and apoptosis-related transcripts during in vivo post-ovulatory oocyte aging in zebrafish Danio rerio (Hamilton, 1822)
Authors: Konar Essaikiammal Sodalai Muthu , Mai Knut , Brachs Sebastian , Waghmare Swapnil Gorakh , Samarin Azadeh Mohagheghi , Policar Tomas , Samarin Azin Mohagheghi 
Published: June 2024

IntroductionPost-ovulatory aging is a time-dependent deterioration of ovulated oocytes and a major limiting factor reducing the fitness of offspring. This process may lead to the activation of cell death pathways like apoptosis in oocytes.MethodologyWe evaluated oocyte membrane integrity, egg developmental competency, and mRNA abundance of apoptosis-related genes by RT-qPCR. Oocytes from zebrafish Danio rerio were retained in vivo at 28.5°C for 24 h post-ovulation (HPO). Viability was assessed using trypan blue (TB) staining. The consequences of in vivo oocyte aging on the developmental competence of progeny were determined by the embryo survival at 24 h post fertilization, hatching, and larval malformation rates.ResultsThe fertilization, oocyte viability, and hatching rates were 91, 97, and 65% at 0 HPO and dropped to 62, 90, and 22% at 4 HPO, respectively. The fertilizing ability was reduced to 2% at 8 HPO, while 72% of oocytes had still intact plasma membranes. Among the apoptotic genes bcl-2 (b-cell lymphoma 2), bada (bcl2-associated agonist of cell death a), cathepsin D, cathepsin Z, caspase 6a, caspase 7, caspase 8, caspase 9, apaf1, tp53 (tumor protein p53), cdk1 (cyclin-dependent kinase 1) studied, mRNA abundance of anti-apoptotic bcl-2 decreased and pro-apoptotic cathepsin D increased at 24 HPO. Furthermore, tp53 and cdk1 mRNA transcripts decreased at 24 HPO compared to 0 HPO.DiscussionThus, TB staining did not detect the loss of oocyte competency if caused by aging. TB staining, however, could be used as a simple and rapid method to evaluate the quality of zebrafish oocytes before fertilization. Taken together, our results indicate the activation of cell death pathways in the advanced stages of oocyte aging in zebrafish.
A New Class of Coordinated Non-Convex Fuzzy-Number-Valued Mappings with Related Inequalities and Their Applications
Authors: Rakhmangulov Aleksandr , Aljohani A. F. , Mubaraki Ali , Althobaiti Saad 
Published: June 2024

Both theoretical and applied mathematics depend heavily on integral inequalities with generalized convexity. Because of its many applications, the theory of integral inequalities is currently one of the areas of mathematics that is evolving at the fastest pace. In this paper, based on fuzzy Aumann’s integral theory, the Hermite–Hadamard’s type inequalities are introduced for a newly defined class of nonconvex functions, which is known as U·D preinvex fuzzy number-valued mappings (U·D preinvex F·N·V·Ms) on coordinates. Some Pachpatte-type inequalities are also established for the product of two U·D preinvex F·N·V·Ms, and some Hermite–Hadamard–Fejér-type inequalities are also acquired via fuzzy Aumann’s integrals. Additionally, several new generalized inequalities are also obtained for the special situations of the parameters. Additionally, some of the interesting remarks are provided to acquire the classical and new exceptional cases that can be considered as applications of the main outcomes. Lastly, a few suggested uses for these inequalities in numerical integration are made.
Syrga2: Post-Quantum Hash-Based Signature Scheme
Authors: Algazy Kunbolat , Sakan Kairat , Nyssanbayeva Saule , Lizunov Oleg 
Published: June 2024

This paper proposes a new post-quantum signature scheme, Syrga2, based on hash functions. As known, existing post-quantum algorithms are classified based on their structures. The proposed Syrga2 scheme belongs to the class of multi-use signatures with state retention. A distinctive feature of state-retaining signatures is achieving a compromise between performance and signature size. This scheme enables the creation of a secure signature for r messages using a single pair of secret and public keys. The strength of signature algorithms based on hash functions depends on the properties of the hash function used in their structure. Additionally, for such algorithms, it is possible to specify the security level precisely. In the proposed scheme, the HBC-256 algorithm developed at the Institute of Information and Computational Technologies (IICT) is used as the hash function. The security of the HBC-256 algorithm has been thoroughly studied in other works by the authors. In contrast to the Syrga1 scheme presented in previous works by the authors, the Syrga2 scheme provides for the definition of different security levels determined by the parameter τ. This paper experimentally demonstrates the impossibility of breaking the proposed scheme using a chosen-plaintext attack. Additionally, the scheme’s performance is evaluated for signature creation, signing, and message verification.
Understorey Plant Functional Traits of Platycladus orientalis Depends on Crown Closure and Soil Properties in the Loess Plateau, China
Authors: Duan Gaohui , Liu Lifeng , Wen Zhongming , Tang Yu , Wang Boheng 
Published: June 2024

The crown closure of Platycladus orientalis forests has a wide-ranging impact on vegetation and soil, thereby affecting the overall functioning of the ecosystem. There is limited research on the effects of the Platycladus orientalis forest crown closure on changes in community plant functional traits, and their interactions are not yet clear. Therefore, we investigated 50 plots of different types of Platycladus orientalis crown closure, and we measured the functional traits of nine shrub species and 68 herb species in 50 plots under five different densities of Platycladus orientalis forests in the Loess Plateau. The consequence of Pearson’s correlation analysis showed significant positive correlations between LC and LTD, LN and LP, LN and LNP, LN and LV, LN and H, LP and LV, LP and H, and SLA and LV (p < 0.05). LC was significantly negatively correlated with LP, LC with SLA, LC with LV, LN with LTD, LP with LNP, LP with LTD, and LTD with H (p < 0.05). Only the soil phosphorus content (SP) and soil water content (SWC) showed a significant positive correlation with multiple plant functional traits. The crown closure of Platycladus orientalis forests increased significantly, as did the plant functional features. Changes in the Platycladus orientalis forest crown closure significantly increased the LC, LV, LN, LP, and SLA in plant functional traits. An increase in Platycladus orientalis forest crown closure significantly increased the soil organic carbon (SC), soil phosphorus content (SP), soil nitrogen content (SN), soil water content (SWC), field capacity (FC), and soil porosity (PO). Based on a structural equation model, we found that, while changes in the Platycladus orientalis forest crown closure did not directly affect plant functional traits, they could indirectly influence these traits through soil factors, primarily the soil water content (SWC) and soil phosphorus content (SP) (p < 0.05). Additionally, the mechanisms of the Platycladus orientalis forest crown closure’s impact on different functional traits vary. The research results provide scientific elements for the ecological restoration of Platycladus orientalis forests on the Loess Plateau.
Metabolic Engineering of Bacillus subtilis for the Production of Poly-γ-Glutamic Acid from Glycerol Feedstock
Authors: Pasotti Lorenzo , Massaiu Ilaria , Magni Paolo , Calvio Cinzia 
Published: June 2024

Poly-γ-glutamic acid (γ-PGA) is an attractive biopolymer for medical, agri-food, and environmental applications. Although microbial synthesis by Bacilli fed on waste streams has been widely adopted, the obtainment of efficient sustainable production processes is still under investigation by bioprocess and metabolic engineering approaches. The abundant glycerol-rich waste generated in the biodiesel industry can be used as a carbon source for γ-PGA production. Here, we studied fermentation performance in different engineered Bacillus subtilis strains in glycerol-based media, considering a swrA+ degU32Hy mutant as the initial producer strain and glucose-based media for comparison. Modifications included engineering the biosynthetic pgs operon regulation (replacing its native promoter with Physpank), precursor accumulation (sucCD or odhAB deletion), and enhanced glutamate racemization (racE overexpression), predicted as crucial reactions by genome-scale model simulations. All interventions increased productivity in glucose-based media, with Physpank-pgs ∆sucCD showing the highest γ-PGA titer (52 g/L). Weaker effects were observed in glycerol-based media: ∆sucCD and Physpank-pgs led to slight improvements under low- and high-glutamate conditions, respectively, reaching ~22 g/L γ-PGA (26% increase). No performance decrease was detected by replacing pure glycerol with crude glycerol waste from a biodiesel plant, and by a 30-fold scale-up. These results may be relevant for improving industrial γ-PGA production efficiency and process sustainability using waste feedstock. The performance differences observed between glucose and glycerol media also motivate additional computational and experimental studies to design metabolically optimized strains.