bluuebunny/crossref_metadata_2025_split huggingface dataset:
Downregulation of IGFBP7 and TIMP-2 protects kidney cells by regulating cell cycle in sepsis-associated acute kidney injury
Authors: Wen Shiyao , Wang Qian , Jia Jia , Gong Xiaoying , Zhao Yang , Li Guofu 
Published: May 2023

Abstract
Background
Tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) are biomarkers for early-stage diagnosis of acute kidney injury (AKI) and mediate the cell cycle transition from G1 to S. However, their pathophysiological roles in AKI remain obscure. Downregulation of IGFBP7 and TIMP-2 protects the kidney in AKI.Here, we aimed to elucidate the underlying mechanism and the contribution of the G1/S cell cycle arrest to AKI.
Methods
CLP and LPS were used to build the sepsis-associated AKI models in vivo and vitro respectively. The cyclinD, cyclinE, and pRB were detected to interpret the relationship between cell cyle arrest and sepsis-associated AKI. Then we studied the cell cycle, apoptosis, and autophagy after knocking-down the gene of IGFBP7 and TIMP-2. Finally, ribociclib was added to explore whether attenuation of LPS-induced apoptosis depend on G1/S cell cycle transition.
Results
Compared to sham mice, mice subjected to cecal ligation and puncture exhibited severe G1/S cell cycle arrest in the kidney and higher urine IGFBP7 and TIMP-2 levels. In vitro, IGFBP7 or TIMP-2 downregulation in lipopolysaccharide-treated HK-2 cells decreased inflammatory cytokine levels, reduced apoptosis and G1/S cell cycle arrest, and increased autophagy, relative to the control group. Furthermore, ribociclib was used to restore the G1/S cell cycle arrest, which was also attenuated by IGFBP7 or TIMP2 siRNA treatments.
Conclusions
Downregulation of IGFBP7 and TIMP-2 protects kidney cells from sepsis-induced acute kidney injury by regulating cell cycle, apoptosis and autophagy, and the protective effects are not totally reversed by alleviating cell cycle arrest.
Untargeted metabolomics analysis of plasma metabolic characteristics in patients with acne and insulin resistance
Authors: He Qingqing , Shu Huiling , Peng Yu , Xu Yang , Liu Li , Zhou Jie , Zhao Juan , Xiong Xia , Li Changqiang 
Published: May 2023

Abstract
Acne vulgaris is a chronic inflammatory disease with high incidence, diverse clinical manifestations, poor clinical efficacy, and easy recurrence. Recent studies have found that the occurrence of acne is related to metabolic factors such as insulin resistance; however, the specific mechanism of action remains unclear. This study aimed to identify significantly different metabolites and related metabolic pathways in the serum of patients with and without insulin resistance and acne vulgaris. LC-MS/MS was used to analyze serum samples from patients with acne and insulin resistance (n = 51) and acne without insulin resistance (n = 69) to identify significant metabolites and metabolic pathways. In this study, 18 significant differential metabolites were screened for the first time. In the positive ion mode, the upregulated substances were creatine, sarcosine, D-proline, uracil, Phe-Phe, L-pipecolic acid, and DL-phenylalanine; the downregulated substances were tridecanoic acid (tridecylic acid), L-lysine, cyclohexylamine, sphingomyelin (d18:1/18:0), gamma-L-Glu-epsilon-L-Lys, and 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine. In the negative ion mode, the upregulated substance was cholesterol sulfate, and the downregulated substances were D(-)-beta-hydroxybutyric acid, myristic acid, D-galacturonic acid, and dihydrothymine. Cholesterol sulfate showed the most significant expression among all differential metabolites (VIP = 7.3411). Based on the KEGG database, necroptosis and ABC transporters were the most significantly enriched metabolic pathways in this experiment. The differential metabolites and pathways identified in this study may provide new possibilities for the clinical diagnosis and development of targeted drugs for acne patients with insulin resistance.
Neurotrophin-loaded PDADMAC/HEPARIN multilayers as an unexpected system to damage neuroblastoma cancer cells
Authors: Dąbkowska Maria , Stukan Iga , Kowalski Bogusław , Donerowicz Wiktoria , Wasilewska Monika , Szatanik Alicja , Stańczyk-Dunaj Małgorzata , Michna Aneta 
Published: May 2023

Abstract

Biomaterial science has contributed tremendously to developing nanoscale materials for delivering biologically active compounds, enhancing protein stability, and enabling its therapeutic use. We describe a process of formation of polyelectrolyte multilayer (PEM) prepared by sequential adsorption of positively charged polydiallyldimethylammonium chloride (PDADMAC) and negatively charged heparin sodium salt (HP), from low polyelectrolyte concentration, on a solid substrate. PEM was further applied as a platform for the adsorption of a brain-derived growth factor (BDNF), which is a protein capable of regulating neuronal cell development. The multilayers containing BDNF were thoroughly characterized by electrokinetic (streaming potential measurements, SPM) and optical (optical waveguide lightmode spectroscopy, OWLS) techniques. It was found that BDNF was successfully adsorbed on polyelectrolyte multilayers, terminated by PDADMAC and HP under physiological conditions. We further explore the effect of established PEMsin vitroon the neuroblastoma SH-SY5Y cell line. An enzyme-linked immunosorbent assay (ELISA) confirmed that BDNF was released from multilayers, and the use of the PEMs intensified its cellular uptake. PEMs significantly inhibited the proliferation of neuroblastoma cancer cells up to 72% and decreased polarization of mitochondrial membrane up to 58% (in relation to control). HPLC analysis showed that both PDADMAC and HP - terminated multilayers have antioxidative properties as they almost by half decreased lipid peroxidation in SH-SY5Y cells. Finally, enhanced formation of spheroid-like, 3D structures was observed by light microscopy. We offer a well-characterized, biodegradable PEM with antioxidant properties acting as BDNF carrier, stabilizing BDNF and making it more accessible to cells in an inhomogeneous, dynamic, and transientin vitroenvironment. Described multilayers can be utilized in future biomedical applications such as boosting the effect of treatment by selective anticancer as adjuvant therapy, and in biomedical research for future development of more precise neurodegenerative disease models, as they enhance cellular 3D structure formation.
First principles-based design of lightweight high entropy alloys
Authors: Sorkin Viacheslav , Yu Zhi Gen , Chen Shuai , Tan Teck Leong , Aitken Zachary , Zhang Yong-Wei 
Published: May 2023

Abstract
Recently, the design of lightweight high entropy alloys (HEAs) with a mass density lower than 5 g/cm3 has attracted much research interest in structural materials. We applied a first principles-based high-throughput method to design lightweight HEAs in single solid-solution phase. Three lightweight quinary HEA families were studied: AlBeMgTiLi, AlBeMgTiSi and AlBeMgTiCu. By comprehensively exploring their entire compositional spaces, we identified the most promising compositions according to the following design criteria: the highest stability, lowest mass density, largest elastic modulus and specific stiffness, along with highest Pugh’s ratio. We found that HEAs with the topmost compositions exhibit a negative formation energy, a low density and high specific Young’s modulus, but a low Pugh’s ratio. Importantly, we show that the most stable composition, Al0.31Be0.15Mg0.14Ti0.05Si0.35 is energetically more stable than its metallic compounds and it significantly outperforms the current lightweight engineering alloys such as the 7075 Al alloy. These results suggest that the designed lightweight HEAs can be energetically more stable, lighter, and stiffer but slightly less ductile compared to existing Al alloys. Similar conclusions can be also drawn for the AlBeMgTiLi and AlBeMgTiCu. Our design methodology and findings serve as a valuable tool and guidance for the experimental development of lightweight HEAs.
Implementation of Delay-Sensitive Smart Healthcare Framework in Cloud and Fog Environment
Authors: Rajpoot Navneet Kumar , Singh Prabhdeep , Pant Bhaskar 
Published: May 2023

Abstract
Smart healthcare systems are novel innovations that can improve healthcare services by giving individuals details about their medical conditions in real time. However, processing and analyzing huge amounts of information stored in these systems can frequently result in latency and interruptions, negatively impacting the system's efficiency. To solve this issue, this research presents an innovative healthcare framework incorporating cloud and fog computing techniques to reduce latency and enhance whole system performance. The framework has three different tiers: the user tier, the fog tier, and the cloud tier. Health-related information is gathered from users in the user tier using cloud pulses. An optimized Ant Colony Optimization load balancing algorithm subsequently monitors this data. The load balancer allocates user requests to fog servers in the fog tier, considering factors including response time and cost. The fog tier is comprised of fog servers that are located in closer proximity to end-users and are tasked with the real-time processing and analysis of data. The cloud tier accommodates vast quantities of healthcare data and facilitates sophisticated analytics and processing functionalities. The performance of the proposed framework was assessed by implementing it on the Cloud Analyst tool and utilizing metrics such as response time, cost, and system throughput. The experiment findings indicate that the proposed framework performs better in mitigating delay in healthcare compared to conventional healthcare systems. The load balancer that was optimized using Ant Colony Optimization algorithm efficiently allocated the workload among the fog servers, resulting in enhanced system response time and decreased latency. The concept of fog computing proved to be highly productive in mitigating latency by enabling local data processing and analysis near the end-user, thereby reducing reliance on the cloud tier. The empirical findings indicate that the framework put forward can transform the provision of healthcare services, rendering them more streamlined, economical, and focused on the needs of patients.
RGCC is a Prognostic Biomarker and Correlates with Immune Infiltrates in Breast Cancer
Authors: Zhang Huiwen , Su Yan , Jia Jianhua , Wang Qi 
Published: May 2023

Abstract
Background
RGCC (regulator of cell cycle) is a protein-coding gene, also known as RGC-32(response gene to complement 32 protein), which is an important regulatory gene of cell cycle progression. However, the relationship between RGCC and breast cancer prognosis and tumor immune cells remains unclear.
Methods and results
RGCC differential expression analysis was performed based on TCGA, GEO, UALCAN and HPA databases, respectively. Then, KM curve and ROC curve were constructed to evaluate the prognosis and diagnostic value of RGCC. In addition, Immune Infiltration Analysis was performed by ssGSEA. scTIME and cancerSEA databases were used to illustrate the relationship between RGCC and tumor immune cells at the single-cell level. Subsequently, the clinical relevance of RGCC was discussed and Nomogram and calibration curves were constructed. Finally, R package clusterProfiler was used for enrichment of the GO (Gene Oncology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways to explore the biological function of RGCC.
Results
Low expression of RGCC in breast cancer was associated with better overall survival (OS) and Disease Specific Survival (DSS), and ROC curve suggested that RGCC had a good diagnostic value. The expression of RGCC was positively correlated with the invasion levels of iDC, Macrophages, Neutrophils, CD8 T cells, and Th1 cells. RGCC was positively correlated with immunoinhibitors TGFB1 and immunostimulators C10orf54, CD40, CXCL12, CXCR4, IL6, NT5E, TNFRSF4, TNFRSF8 and TNFSF9 in BRCA. Single cell data showed that RGCC was highly expressed in Macrophages. RGCC mRNA expression was significantly correlated with Age, Histological type, T stage, HER2 status and PAM50. Mechanistically, we found that RGCC is closely related to cell adhesion and MHC Class II protein complexes. RGCC was associated with angiogenesis in two single-cell datasets.
Conclusions
RGCC may play an important role in cell proliferation and metastasis, and can be used as a prognostic biomarker to determine the prognosis of BRCA and immune invasion.
The efficacy and markers of recurrence of stereotactic body radiation therapy alone for hepatocellular carcinoma with the portal vein invasion (≤5 cm)
Authors: Jia Jun , Sun Jing , Li Dong , He Wei-ping , Zhang Ai-min , Li Wen-gang , Duan Xuezhang 
Published: May 2023

Abstract
Background and Aims: To evaluate the efficacy and safety of stereotactic body radiation therapy (SBRT) in patients with the portal vein invasion (≤5 cm) and explore the association between pretreatment platelet count and out-field recurrence and radiation-induced liver disease (RILD).
Methods: A total of 490 HCC patients whose single lesion with the portal vein invasion (≤5 cm) treated with SBRT were included in our study. 334 patients were retrospectively enrolled and 156 patients were prospectively included in our investigation respectively.
Results: The 1-, 3- and 5-year overall survival (OS) rates were 96.7%, 80.6% and 72.3%, respectively. The 1-, 3- and 5-year progression free survival (PFS) rates were 80.5%, 58.4% and 45.1%, respectively. The 1-, 3- and 5-year distant metastasis-free survival (DMFS) rates were 82.2%, 61.8% and 48.3%, respectively. The 1-, 3- and 5-year local control (LC) rates were 98.2%, 95.1% and 93.5%, respectively. A lower pretreatment PLT count was found to be associated with worse OS rates (HR 0.990, 95% CI 0.985-0.996, p=0.001*), PFS rates (HR 0.995, 95% CI 0.993-0.998, p=0.001*) and higher occurrence rates of RILD (HR 0.978, 95% CI 0.965-0.991, p=0.001*).
Conclusions: SBRT was a safe and effective option in patients with the portal vein invasion (≤5 cm), which had shown good LC, OS rates and low toxicity. The platelet count could predict out-field recurrence and RILD.
The mixed solutions of the (2 + 1)-dimensional Hirota-Satsuma-Ito equation and the analysis of nonlinear transformed waves
Authors: An Yongning , Guo Rui 
Published: May 2023

Abstract
In this paper, we obtain the N-soliton solution for the (2 + 1)-dimensional Hirota-Satsuma-Ito equation by the Hirota bilinear method. On this basis, the breathers and lumps can be obtained using the complex conjugate parameter as well as the long wave limit method, and the mixed solutions containing them are investigated. Then, different nonlinear transformed waves are obtained from breathers and lumps under specific conditions, which include quasi-anti-dark soliton, M-shaped soliton, oscillation M-shaped soliton, multi-peak soliton, quasi-periodic soliton and W-shaped soliton. Finally, on the basis of the two-breather solutions, we discuss in detail the mixed solutions consisting of one breather and one nonlinear transformed wave, and the mixed solutions formed by two nonlinear transformed waves.
Multidomain Interventions for Non-pharmacological Enhancement (MINE) Program in Chinese Older Adults with Mild Cognitive Impairment: A Multi-center Cluster Randomized Controlled Trial Protocol
Authors: Wu Xiaochu , Zhang Tianyao , Tu Yanhao , Deng Xueling , A Sigen , Li Yuxiao , Jing Xiaofan , Wei Lixuan , Huang Ning , Cheng Ying , Deng Linghui , Jia Shuli , Du Yingshi , Liu Yongming , Li Xiuli , He Yan , Gao Yanling , Zhou Lihua , Zhang Qin , Yang Yongxue , Li Jun , Jiang Ning , Dong Birong 
Published: May 2023

Abstract
Background
Dementia is characterized by insidious onset, difficult early diagnosis, and unclear pathogenesis without effective treatment. Therefore, the best intervention window is mild cognitive impairment (MCI) in pre-dementia. There are significant differences in health awareness, living customs, and daily behaviors among Chinese older adults compared to Europeans and Americans. Because the synergistic benefits of multidomain non-pharmacological interventions are consistent with the multifactorial pathogenicity of MCI, such interventions are more appealing, easier to adhere to, and more relevant to daily life than single-mode interventions. This study aims to investigate and validate multidomain intervention strategies for MCI patients based on Chinese population characteristics, establish a biological sample and image database to investigate the pathogenesis and pathways of cognitive impairment, and develop digital tools for MCI early intervention based on deep learning technology.
Methods
Our study was designed as a national multi-center, double-blind, community-based cluster randomized controlled trial (RCT). Twelve medical institutions in ten Chinese cities will participate in our study from 2022 to 2024, and 1080 community residents aged 50 and above will be enrolled as participants. Each sub-center will be responsible for 90 participants (30 people per community) across three communities (blank control group, health education group, and multidomain intervention group). All data gener–ated by the research will be analyzed and processed by statistical software (such as SPSS, R, etc.), and part of the research data will be displayed in the form of graphs and tables. The community will be the basic unit of the present study, and all participants in each community will receive the same intervention/control measure.
Discussion
As the optimal intervention window for the prevention of dementia, there is a lack of research evidence based on Southeast Asian population for mild cognitive impairment. Multidomain intervention is more in line with the diversified composition of lifestyle of the elderly. Compared with single intervention, the compliance of intervention objects is higher and easier to adhere to. Through the changes and comparison of subjects' biological sample information before and after the intervention, the biological targets and potential mechanisms related to cognitive intervention were explored.
Trial registration
ChiCTR2000035012
Prognosis of extracorporeal membrane oxygenation (ECMO) treatment on cardiac shock after acute myocardial infarction: A bioinformatic analysis
Authors: Liu Chuanzhen , Wei Kaiming , Lv Xin , Gu Xinghua , Liu Shuqin 
Published: May 2023

Abstract
Background
Cardiac shock after acute myocardial infarction becomes more common with age and the improvement of living standards. Extracorporeal membrane oxygenation (ECMO) is an effective treatment for such patients. However, genes and molecular processes that can predict the prognosis of shock after acute myocardial infarction with ECMO treatment are not known. Methods: The microarray dataset (GSE93101) was retrieved from the gene expression omnibus (GEO) online database. Differential expression, weighted gene co-expression network analyses (WGCNA), gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were performed. In order to find the first five hub genes, we used the mutual construction of the PPI network and the Cytoscape software. And then, the gene-miRNA network was performed to determine the regulated miRNAs of the hub genes. Results: 10 genes were obtained when those in the two highest correlation modules of WGCNA were intersected with the differential genes. 104 differential genes were found to be associated with oxidoreductase activity and metabolic pathways. We found the first five hub genes using the Cytoscape software: CD68, C8A, NR1H4, and ADGRE1 genes were downregulated while TMPRSS6 was upregulated. TMPRSS6 had the highest degree of affinity and was regulated by 29 miRNAs, while CD68, NR1H4, CD163, and C8A were regulated by 18, 14, 14, and 2 miRNAs, respectively. Conclusion: Through comprehensive analysis, CD68, which was regulated by 18 miRNAs, was found to be associated with the prognosis of ECMO after acute myocardial infarction (AMI), and the mechanism may be associated with macrophage differentiation.
In vivo reprogramming of macrophages using pro-resolving factors to resolve experimental CNS inflammation
Authors: Gauthier Thierry , Martin-Rodriguez Omayra , Chagué Cécile , Daoui Anna , Ceroi Adam , Varin Alexis , Bonnefoy Francis , Valmary-Degano Séverine , Couturier Mélanie , Behlke Susanne , Saas Philippe , Perruche Sylvain 
Published: May 2023

Abstract
Background
Reinstating inflammation resolution presents an innovative concept to regain inflammation control in diseases marked by chronic inflammation. While most therapeutics target inflammatory molecules and inflammatory effector cells and mediators, targeting macrophages to initiate inflammation resolution to control neuroinflammation has not yet been attempted. Resolution-phase macrophages are critical in the resolution process to regain tissue homeostasis, and are programmed through the presence and elimination of apoptotic leukocytes. Hence inducing resolution-phase macrophages might represent an innovative therapeutic approach to control and terminate dysregulated neuroinflammation.
Methods
Here, we investigated if the factors released by in vitro induced resolution-phase macrophages (their secretome) are able to therapeutically reprogram macrophages to control ongoing chronic neuroinflammation in the model of experimental autoimmune encephalomyelitis (EAE).
Results
We found that injection of the pro-resolutive secretome reduced demyelination and decreased inflammatory cell infiltration in the CNS, notably through the in vivo reprogramming of macrophages at the epigenetic level. Adoptive transfer experiments with macrophages in vivo or in vitro reprogrammed with such pro-resolutive secretome confirmed the stability and transferability of this acquired therapeutic activity.
Conclusions
Overall, our data confirm the therapeutic activity of a pro-resolution secretome in the treatment of ongoing CNS inflammation, via the epigenetic reprogramming of macrophages and open with that a new therapeutic avenue for diseases marked by neuroinflammation.
Identification of shared genes of atherosclerosis and Crohn's disease based on bioinformatics and machine learning algorithm
Authors: Cao Ye , Li Bo , Xia Nan , Zhang Jian-Cheng 
Published: May 2023

Abstract
Background: Atherosclerosis (AS) is a major contributor to cardiovascular mortality and morbidity globally. There is currently a dearth of information about Crohn's disease (CD) and its relation to the risk of atherosclerotic cardiovascular disease. However, recent studies were unable to identify the biological mechanism at the genetic level.
Methods: Four microarray datasets (GSE43292, GSE28829, GSE186582, and GSE102133) were downloaded from the Gene Expression Omnibus database. The Limma package was used to identify differentially expressed genes (DEGs) in AS and CD. Functional enrichment analysis, protein-protein interaction (PPI) network construction, and machine learning algorithms were applied to identify hub genes. Then the hub genes were calculated based on the receiver operating characteristic (ROC) curve. Subsequently, we conducted single-gene GSEA analysis and immune infiltration analysis to further investigated the possible mechanism of the hub genes.
Results: A total of 24 common upregulated DEGs and 10 common downregulated DEGs were observed in AS and CD. According to enrichment analyses, these genes were connected with immune-related and inflammation-related signaling pathways. Three hub genes (IL1RN, TNFSF13B, PRDM1) were identified. The AUC of hub genes was higher than 0.7 and the AUC of the hub genes-based logistic regression model was 0.873. Single-gene GSEA analysis and immune infiltration analysis found the hub genes were associated with AS in CD patients, and there were some associations between hub genes and 22 immune cells.
Conclusion: We identified and validated 3 hub genes (IL1RN, TNFSF13B, PRDM1) as biomarkers in AS and CD. This study may provide a new perspective on the pathogenesis of AS and CD comorbidity.