bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism study of oleanolic acid derivative, K73-03, inducing cell apoptosis in hepatocellular carcinoma
Authors: Wang Jiaqi , Ma Chuchu , Tang Zhongyuan , Sun Zhengwu , Qaed Eskandar , Chi Xinming , Wang Jun , Jamalat Yazeed , Geng Zhaohong , Tang Zeyao , Yao Qiying 
Published: May 2023

Abstract
Oleanolic acid (3β-hydroxyolean-12-en-28-oic acid, OA) is a kind of pentacyclic triterpene, which widely distributes in nature. OA possesses a powerful anti-cancer effect; however, its low solubility limits its bioavailability and application. In this study, a new OA derivative, K73-03, was used to determine its effect on liver cancer cells and detailed molecular mechanisms. We found that K73-03 could significantly inhibit the cell viability, migration and colony formation of SMMC-7721 and HepG2 cells in a dose-dependent manner, having a stronger effect on HepG2 cells. Excess ROS was produced when treated with K73-03 compared with the control group. After adding a reactive oxygen scavenger, N-acetyl-L-cysteine (NAC), the expression of ROS was downregulated. For mitochondrial dysfunction, K73-03 could reduce Mitochondrial membrane potential (∆Ψm) and inhibit cell respiration. In mechanism studies, the ratio of Bax/Bcl-2 and the expressions of cleaved-caspase9 and cleaved-caspase3 in HepG2 cells were upregulated after K73-03 treatment, while the ratio of LC3B-II/I and the expression of Beclin1 were also increased. The protein expressions of p-JAK2, p-STAT3, COX-2, p65 and p-65 in K73-03 treated HepG2 cells were downregulated and the nuclear translocation of p65 was inhibited. In our study, K73-03 may lead to the disorder of mitochondria in HepG2 cells, leading to excessive ROS production and apoptosis in cells. Meanwhile, K73-03 could induce cell apoptosis by inhibiting JAK2/STAT3 pathway and NF-κB/P65 pathway.
A resistivity-based experimental compaction model for Yunnan laterite
Authors: PENG Guangcan , XU Xingqian , ZHAO Xi , QU Xin , WANG Haijun 
Published: May 2023

Abstract
Soil resistivity can effectively reflect the variation in structural characteristics of soils. The changes in soil resistivity can indirectly represent the degree of soil compaction, which is of great significance for the rapid evaluation of soil compaction. Yunnan laterite, in China, has widely been used as a building material in foundations, roadbeds, and dams due to its high strength and low compression. In this work, we tested the vertical and lateral resistivity of laterite during consolidation compression through an improved consolidation compression resistivity tester to discuss the variations in resistivity structural characteristic parameters (structural factor, shape factor, and anisotropy coefficient). A comprehensive index of resistivity structure characteristics was proposed to create a compactness evaluation model of laterite. The results showed that the vertical resistivity, lateral resistivity, average structural factor, and average shape factor of laterite gradually increased with continuous multi-stage vertical loading; however, the anisotropy coefficient decreased first, and then slowly increased to a stable state. The comprehensive index of resistivity structure characteristics could indirectly reflect the water content and pore content of the laterite, and the lateral resistivity was predicted from the vertical resistivity. Considering the influence of saturation and porosity on the resistivity structure characteristics, the evaluation model of compaction for laterite was finally established based on resistivity characteristics and this model had high accuracy, with small model verification error and good applicability. The proposed prediction model could serve as a theoretical reference for the application of the high-density electrical method in the convenient detection of compaction for laterite rolling engineering.
Vertebral venous plexus abnormalities in a young Poodle causing chronic lameness
Authors: Vedel Tanja , Heidemann Pernille Lindholm , Koch Bodil Cathrine , Leifsson Páll S. , McEvoy Fintan J. , Gredal Hanne 
Published: May 2023

Abstract
Background

Chronic progressive lameness in young dogs which do not show abnormalities on initial, survey imaging, is diagnostically challenging. The present case had undergone extensive diagnostics without definitive diagnosis until magnetic resonance imaging (MRI) allowed lesion detection and localization to the vertebral venous system. Abnormalities of the vertebral venous system have only previously been reported once in veterinary medicine.

Case presentation

A 1-year-old intact male Standard Poodle was referred with a history of chronic and progressive right thoracic limb lameness. A full work up which included routine haematology, serum biochemistry, radiography, and native computed tomography (CT) of the affected thoracic limb was performed at the referring veterinarian and reported as normal. Management including conventional pain medication, laser treatment, and physiotherapy had been attempted unsuccessfully. Treatment with meloxicam (0.1 mg/kg per os daily) did, however, have some effect on the dog’s pain according to the owner. At our hospital the right thoracic limb lameness was confirmed. A pain reaction was found on manipulation of both shoulders, and a marked muscle atrophy was noted around the right shoulder. On neurological examination, the right thoracic limb had decreased muscle tone and a decreased withdrawal reflex localizing the problem to a right-sided C6-T2 myelopathy or radiculopathy. MRI of the cervicothoracic spine and both brachial plexuses was performed. This showed enlarged internal vertebral venous plexuses especially on the right side from the level of C6 -T2 vertebrae together with marked contrast enhancement of the nerve roots in this region, suggesting nerve root compression secondary to the enlarged venous system. Further analgetic medical management was attempted but due to progression of the dog’s clinical signs, euthanasia was elected 5 months later. Post-mortem investigations confirmed imaging findings and found loss of neurons and swelling of the axons at the compressive sites on histopathology.

Conclusions

Based on the imaging findings a diagnosis of venous plexus abnormalities with secondary radiculopathy was considered most likely. This was confirmed by the post-mortem investigation. Venous plexus abnormalities are rare but should be considered in young dogs with progressive signs of lameness and regional muscle atrophy in which the underlying cause is not identified with conventional diagnostics.
Impacts of Improved Horizontal Resolutions in the Simulations of Mean and Extreme Precipitation using CMIP6 HighResMIP Models over West Africa
Authors: Ajibola Felix Olabamiji , Afolayan Stella Abosede 
Published: May 2023

Abstract
We analyzed 16 historical simulations from High-Resolution Model Intercomparison Project (HighResMIP) within the framework of Coupled Model Intercomparison Project (CMIP) Phase 6 (CMIP6). The simulations comprise high and low-resolution simulations. The aim is to examine the effect of improved horizontal resolution models on mean and extreme precipitation over West Africa from 1985 – 2014. Observation shows southeast and southwest regions are the most active in precipitation, consistent with simulations of HighResMIP. The impact of improved horizontal resolutions is felt in the simulation of orographic-induced rainfall over the high grounds and the intensification of precipitation in most of the metrics employed. The observed highest 1-day precipitation shows most of the Guinea coast region had 1-day rainfall greater than 100 mm, which was over-estimated (under-estimated) by high (low) resolution simulations. Also, improvement in horizontal resolution seems to improve the capacity of high-resolution models to reproduce the observed pattern of heavy precipitation (R10mm) days and very heavy rainfall (R20mm) days. The spatio-temporal analysis showed the presence of uncertainty in the simulation of both the high and low resolutions simulations in reproducing the extreme precipitation over West Africa. Due to this, a bias correction approach was employed.
Proteomic analysis of mesenchymal stromal cells secretome in comparison to leukocyte- and platelet-rich fibrin
Authors: Al-Sharabi Niyaz , Gruber Reinhard , Sanz Mariano , Mohamed-Ahmed Samih , Kristoffersen Einar K , Mustafa Kamal , Shanbhag Siddharth 
Published: May 2023

Abstract
Secretomes of mesenchymal stromal cells (MSC) are emerging as a novel growth factor (GF)-based strategy for periodontal and bone regeneration. The objective of this study was to compare the secretome of human bone marrow MSC (BMSC) to that of leukocyte- and platelet-rich fibrin (L-PRF), an established GF-based therapy, in the context of wound healing and regeneration. Conditioned media from human BMSC (BMSC-CM) and L-PRF (LPRF-CM) were subjected to quantitative proteomic analysis using liquid chromatography with tandem mass spectrometry. Global profiles, gene ontology (GO) categories, differentially expressed proteins (DEPs), and gene set enrichment (GSEA) were identified using bioinformatic methods. Concentrations of selected proteins were determined using a multiplex immunoassay. Among the proteins identified in BMSC-CM (2157 proteins) and LPRF-CM (1420 proteins), 1283 proteins were common. GO analysis revealed similarities between the groups in terms of biological processes (cellular organization, protein metabolism) and molecular functions (cellular-/protein-binding). Notably more DEPs were identified in BMSC-CM (n=550) compared to LPRF-CM (n=118); these included several key GF, cytokines, and extracellular matrix (ECM) proteins involved in wound healing. GSEA revealed enrichment of ECM (especially bone-ECM) related processes in BMSC-CM and immune-related processes in LPRF-CM. Similar trends for inter-group differences in protein detection were observed in the multiplex analysis. Thus, while the secretomes of both BMSC and L-PRF are favourable for wound healing, BMSC-CM is additionally enriched for proteins/processes relevant for periodontal and bone regeneration.
Limit Theorem for a Rough Differential Equation with a Negative Long-Range Random Coefficient
Authors: Bedhiafi Mounir , Gaidi Mohamed 
Published: May 2023

Abstract
We consider an ordinary differential equation driven by rough paths, in the T. Lyons sense \cite{Ly}, depending on a small parameter and with a negative long-range random coefficient. We establish sufficient conditions under which the solution of this ordinary differential equation converges to the solution of a stochastic differential equation driven by a fractional Brownian motion with Hurst parameter \(H\in( \frac{1}{4},\frac{1}{2})\), depends on the asymptotic behavior of the covariance function of the random coefficient.
Cardiopulmonary physiological effects of diuretic therapy in preterm infants with chronic pulmonary hypertension
Authors: Zhu Faith , Rios Daniel Ibarra , Joye Sebastien , Baczynski Michelle , Rios Danielle , Giesinger Regan , McNamara Patrick , Jain Amish 
Published: May 2023

Abstract
Objective
Using targeted neonatal echocardiography (TNE) to examine cardiopulmonary physiological impact of diuretics in preterm infants with chronic pulmonary hypertension (cPH).
Study Design
Retrospective study comparing TNE indices pre- and ≤ 2 weeks (post) of initiating diuretic therapy in infants born < 32 weeks gestational age with cPH.
Results
Twenty-seven neonates with mean gestational age, birthweight and interval between pre-post diuretic TNE of 27.0±2.8 weeks, 859±294 grams, and 7.8±3.0 days respectively were studied. Diuretics was associated with improvement in pulmonary vascular resistance [pulmonary artery acceleration time (PAAT); 34.27(9.76) vs. 40.24(11.10)ms, p=0.01), right ventricular (RV) ejection time:PAAT ratio [5.92(1.66) vs. 4.83(1.14), p<0.01)], RV fractional area change [41.6(9.8) vs. 46.4(6.5%), p = 0.03)] and left ventricular myocardial performance index [0.55(0.09) vs. 0.41(0.23), p < 0.01)]. Post-treatment, frequency of bidirectional/right-to-left inter-atrial shunts decreased significantly (24% vs. 4%, p = 0.05).
Conclusion
Primary diuretic treatment in neonates with cPH may result in improvement in PVR, RV and LV function and compliance.
FSP1 and NRF2 independently contribute to ferroptosis resistance in KEAP1 mutant non-small cell lung carcinoma
Authors: KIM JongWoo , Kim Min-Ju , Han Tae-Hee , Lee Ji-Yoon , Kim Sangok , Kim Hyerin , Oh Kyoung-Jin , Kim Won-Kon , Han Baek-Soo , Bae Kwang-Hee , Ban Hyun Seung , Bae Soo Han , Lee SC , Lee Haeseung , Lee Eun-woo 
Published: May 2023

Abstract
Ferroptosis, a type of cell death induced by lipid peroxidation, has emerged as a novel anti-cancer strategy. Cancer cells frequently acquire resistance to ferroptosis. However, the underlying mechanisms are poorly understood. To address this issue, we conducted a thorough investigation of the genomic and transcriptomic data derived from hundreds of human cancer cell lines and primary tissue samples, with a particular focus on non-small cell lung carcinoma (NSCLC). It was observed that mutations in Kelch-like ECH-associated protein 1 (KEAP1) and subsequent nuclear factor erythroid 2-related factor 2 (NRF2, also known as NFE2L2) activation are strongly associated with ferroptosis resistance in NSCLC. Additionally, AIFM2 gene, which encodes ferroptosis suppressor protein 1 (FSP1),was identified as the gene most significantly correlatedwith ferroptosis resistance, followed by multiple NRF2 targets. We found that inhibition of NRF2 alone was not sufficient to reduce FSP1 protein levels and promote ferroptosis, whereas FSP1 inhibition effectively sensitized KEAP1-mutant NSCLC cells to ferroptosis. Furthermore, we found that combined inhibition of FSP1 and NRF2 induced ferroptosis more intensely. Our findings imply that FSP1 is a crucial suppressor of ferroptosis independent of NRF2 and that synergistically targeting both FSP1 and NRF2 may be a promising strategy for overcoming ferroptosis resistance in cancer.
Microbial Upcycling of Polyethylene into Recombinant Proteins
Authors: Connor Alexander , Lamb Jessica , Delferro Massimiliano , Koffas Mattheos , Zha Runye 
Published: May 2023

Abstract
Herein, we report the development of a new strain of Pseudomonas bacteria capable of upcycling deconstructed polyethylene into high value bespoke recombinant protein products. Using hexadecane, a proxy for depolymerized polyethylene, as a sole carbon nutrient source, we optimized media compositions that facilitate robust biomass growth, with results suggesting the benefits of lower hydrocarbon concentrations and the use of NH4Cl as a nitrogen source. We genomically integrated recombinant genes for green fluorescent protein and spider dragline-inspired silk protein, and we showed their expression in Pseudomonas aeruginosa, reaching titers of approximately 10 mg/L when hexadecane was used as the sole carbon source. Lastly, we demonstrated that chemically depolymerized polyethylene, comprised of a mixture of branched and unbranched alkanes, could be upcycled into silk protein by Pseudomonas aeruginosa at titers of 11.3 ± 1.1 mg/L. Thus, this work establishes a versatile microbial platform for valorizing recalcitrant plastic waste.
Limited water outflux from the subducted slab serpentinite via Mariana arc-basin magmatism
Authors: Zhao Si-Yu , Zhou Zhiyuan , Tamura Yoshihiko , Ma Jinlong , Xu Yi-Guang , Zhang Shao-Wei , Zhao Tai-Ping , Yang Alexandra Yang 
Published: May 2023

Abstract

The water cycle between Earth’s surface and interior controls the long-term stability of sea level. The discovery of ~24-km thick serpentinized mantle in the Pacific plate outside of the Mariana Trench suggests that water influx by plate subduction could be three times greater than previous estimates. However, the extent to which water hosted in the slab serpentinite is released by magmatism remains unclear. Here we present new boron isotopic data on Mariana frontal- and rear-arc volcanics, along with literature data on d11B, halogens and water, to examine the role of slab serpentinite in Mariana arc-basin magmatism. Our results indicate that the contribution of slab serpentinite occurs only in rear-arc volcanics, but is largely invisible in other Mariana arc-basin volcanics. Additionally, quantitative calculations suggest that the water influx of slab crust is sufficient to account for the water outflux through Mariana arc-basin magmatism, demonstrating a limited role of slab serpentinite. Given the extensive slab serpentinization inferred from well-developed bending faults throughout the entire Mariana arc system in the subducting plate, subduction of the 24-km slab serpentinite could potentially carry ~80% of bound water in the subducted slab to the mantle outside of the typical subduction zone region.
Factors affecting hemorrhagic events in patients with advanced lung cancer: from the Rising-VTE/NEJ037 study
Authors: Kawakado Keita , Tsubata Yukari , Hotta Takamasa , Yamasaki Masahiro , Ishikawa Nobuhisa , Fujitaka Kazunori , Kubota Tetsuya , Kobayashi Kunihiko , Isobe Takeshi 
Published: May 2023

Abstract
Background: Despite the occurrence of various hemorrhagic events during the treatment of advanced lung cancer, few studies have reported on their risk factors. In addition, the development of cancer-related thromboembolism indicates the use of anticoagulants. However, adverse events such as bleeding should be monitored. This study aimed to identify the factors that influence the onset of hemorrhagic events in patients with advanced lung cancer.
Methods: The Rising-VTE/NEJ037 study was a multicenter, prospective, observational study. A total of 1008patients with lung cancer who were unsuitable for radical resection or radiation were enrolled and followed up for 2 years. Multivariate analysis using a Cox proportional hazard model was performed to compare the outcomes of the time to the onset of hemorrhagic events for 2 years after registration.
Results: Hemorrhagic events occurred in 115 patients (11.4%), of which 35 (30.4%) had major bleeding events. The factors that significantly increased the risk of hemorrhagic events were venous thromboembolism (VTE) and an Eastern Cooperative Oncology Performance Status score of 1. The factors that significantly reduced the risk of hemorrhagic events were female sex and M1a status.
Conclusion: VTE is a risk factor for hemorrhagic events in patients with advanced lung cancer, and risks associated with anticoagulant therapy should be considered.
Molecular Function Validation and Prognostic Value Analysis of the Cuproptosis-Related Gene Ferredoxin 1 in Colon Cancer
Authors: Feng Ranran , Chen Yong , Shi Lei , Tian Ziying , Yan Shiqi , Jiang Su , Zhang Wenling 
Published: May 2023

Abstract
Background
Cuproptosis is the most recently discovered form of regulated cell death (RCD) induced by intracellular copper. Growing evidence has indicated that cuproptosis plays a considerable role in tumorigenesis among various cancers. However, the role of cuproptosis in the development of colon cancer (CC) and its prognostic value remains to be investigated.
Methods
Five independent cohorts with CC were included in this study. Comprehensive bioinformatics analyses were used to explore the expression, molecular function, and prognostic value of the pivotal regulator of cuproptosis, ferredoxin 1 (FDX1). Correlation analyses and least absolute shrinkage and selection operation (LASSO) regression analyses were utilized to screen the optimal combination of cuproptosis-related genes for constructing a Cox proportional hazards model, and the cuproptosis-related risk score (CRRS) was calculated to stratify CC patients in prognosis. The immunology, tumor stemness index, and drug sensitivity of the CRRS-based subgroups were also investigated. Moreover, the expression and biological functions of FDX1 were validated in vitro.
Results
Results showed that FDX1 was significantly downregulated in CC and its lower expression indicated poorer outcomes. Seven cuproptosis-associated genes were selected to construct the prognostic model. CRRS displayed good performance in predicting prognosis compared with clinical features. Moreover, CRRS could significantly enhance the prognostic prediction precision of the classic tumor, nodes, and metastases (TNM) staging system. The high-CRRS group showed an obvious immunosuppressive microenvironment and a lower stemness index compared with the low-CRRS group. The difference in FDX1 expression between CC and normal tissues was verified in vitro. Overexpression of FDX1 promoted cell death and inhibited cell proliferation and migration.
Conclusions
Our results suggest that CRRS can function as a good prognostic indicator for CC patients and may help guide treatment management. Our findings provide new insights into cuproptosis-targeted therapies for CC patients.
Association between dried fruit intake and DNA methylation: A Multivariable Mendelian Randomization Analysis
Authors: Wu Lingling , Pei Hua , Zhang Yanyan , Zhang Xingxing , Feng Minhua , Yuan Lin , Guo Meixiang , Wei Yuanhao , Tang Zhen , xiang xiqiao 
Published: May 2023

Abstract
Background
Observational studies have reported associations between dried fruit intake and DNA methylation(DNAm). However, inherent flaws in observational study designs make them susceptible to confounding and reverse causality bias. Consequently, it is unclear whether a causal association exists. In the present study, we aimed to investigate the causal associations between dried fruit intake and DNAm.
Methods
We performed two-sample Mendelian randomization (MR) using the IEU Open GWAS database aggregated data. Forty-three single nucleotide polymorphisms (SNPs) associated with dried fruit intake as instrumental variables (IVs) were selected as exposure. DNAm outcomes include Gran (estimated granulocyte proportions); AgeAccelGrim(GrimAge acceleration); Hannum (Hannum age acceleration); IEAA(Intrinsic epigenetic age acceleration), AgeAccelPheno( PhenoAge acceleration), and DNAmPAIadjAge (DNAm-estimated plasminogen activator inhibitor-1 levels). Inverse variance weighted (IVW) method was the primary method for MR analysis, complemented by four other MR methods to ensure the stability and reliability of the results. Additional sensitivity analyses were also performed. The direct effects of dried fruit intake on DNAm were estimated using multivariable mendelian randomization (MVMR).
Results
Univariate MR results showed that for each standard deviation increase in dried fruit intake, the risk of AgeAccelGrim was reduced by 77.7% [odds ratio (OR) = 0.223, 95% confidence interval (CI) = 0.081–0.612; PIVW=3.588×10− 3], and the risk of AgeAccelPheno was reduced by 81.7% (OR = 0.183, 95%CI = 0.054–0.621, PIVW=6.426×10− 3). However, the effects on Gran(PIVW=0.264), Hannum(PIVW=0.299), IEAA(PIVW=0.700), and DNAmPAIadjAge(PIVW=0.051) were not statistically significant. MVMR results adjusting for the potential effects of confounders showed that the causal relationship between dried fruit intake and AgeAccelGrim (PIVW=2.482×10− 2) persisted, but the effect on AgeAccelPheno (PIVW=0.052) was not statistically significant. Sensitivity analysis showed that our results were stable and reliable.
Conclusion
Our MR findings suggest that increased dried fruit intake is associated with slower AgeAccelGrim, providing a promising avenue for exploring the beneficial effects of dried fruit intake on lifespan extension.