bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening and Identification of Hub Genes in the Development of Early Diabetic Kidney Disease Based on Weighted Gene Co-Expression Network Analysis
Authors: Wei Ran , Qiao Jingtao , Cui Di , Pan Qi , Guo Lixin 
Published: June 2022

ObjectiveThe study aimed to screen key genes in early diabetic kidney disease (DKD) and predict their biological functions and signaling pathways using bioinformatics analysis of gene chips interrelated to early DKD in the Gene Expression Omnibus database.MethodsGene chip data for early DKD was obtained from the Gene Expression Omnibus expression profile database. We analyzed differentially expressed genes (DEGs) between patients with early DKD and healthy controls using the R language. For the screened DEGs, we predicted the biological functions and relevant signaling pathways by enrichment analysis of Gene Ontology (GO) biological functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways. Using the STRING database and Cytoscape software, we constructed a protein interaction network to screen hub pathogenic genes. Finally, we performed immunohistochemistry on kidney specimens from the Beijing Hospital to verify the above findings.ResultsA total of 267 differential genes were obtained using GSE142025, namely, 176 upregulated and 91 downregulated genes. GO functional annotation enrichment analysis indicated that the DEGs were mainly involved in immune inflammatory response and cytokine effects. KEGG pathway analysis indicated that C-C receptor interactions and the IL-17 signaling pathway are essential for early DKD. We identified FOS, EGR1, ATF3, and JUN as hub sites of protein interactions using a protein–protein interaction network and module analysis. We performed immunohistochemistry (IHC) on five samples of early DKD and three normal samples from the Beijing Hospital to label the proteins. This demonstrated that FOS, EGR1, ATF3, and JUN in the early DKD group were significantly downregulated.ConclusionThe four hub genes FOS, EGR1, ATF3, and JUN were strongly associated with the infiltration of monocytes, M2 macrophages, and T regulatory cells in early DKD samples. We revealed that the expression of immune response or inflammatory genes was suppressed in early DKD. Meanwhile, the FOS group of low-expression genes showed that the activated biological functions included mRNA methylation, insulin receptor binding, and protein kinase A binding. These genes and pathways may serve as potential targets for treating early DKD.
TangShenWeiNing Formula Prevents Diabetic Nephropathy by Protecting Podocytes Through the SIRT1/HIF-1α Pathway
Authors: Chang Jing , Zheng Jinsu , Gao Xia , Dong Hengbei , Yu Haitian , Huang Mengxiu , Sun Zhencheng , Feng Xiaomeng 
Published: June 2022

BackgroundDiabetic nephropathy (DN) represents a major complication of diabetes, and podocyte injury has a critical function in DN development. TangShenWeiNing formula (TSWN) has been demonstrated to efficiently decrease proteinuria and protect podocytes in DN. This work aimed to explore the mechanism by which TSWN alleviates DN and protects podocytes.MethodsThe major bioactive components of TSWN were detected by mass spectrometry (MS) and pharmacological databases. Eight-week-old male C57BLKS/J db/m and db/db mice were provided pure water, valsartan, low dose TSWN, middle dose TSWN and high dose TSWN by gavage for 12 weeks, respectively.ResultsMS and network pharmacology analyses suggested that TSWN might prevent DN through the sirtuin (SIRT)1/hypoxia-inducible factor (HIF)-1α pathway. Diabetic mice showed elevated urinary albumin in comparison with non-diabetic mice, and TSWN decreased urinary albumin in diabetic mice. Histological injury increased in the kidney in diabetic mice, which could be improved by TSWN. Fibrosis and collagen I expression were induced in the diabetic mouse kidney in comparison with the non-diabetic mouse kidney; TSWN alleviated these effects. Apoptosis and cleaved caspase-3 were induced in the diabetic mouse kidney in comparison with the non-diabetic mouse kidney, and TSWN blunted these effects. Podocytes were damaged in the diabetic mouse kidney, which was improved by TSWN. Podocin and nephrin amounts were decreased in the diabetic mouse kidney in comparison with the non-diabetic mouse kidney, and podocalyxin was increased in urine of diabetic animals in comparison with non-diabetic counterparts. After TSWN treatment, podocin and nephrin were raised in the diabetic mouse kidney, and urinary podocalyxin was depressed in diabetic animals. Diabetic mice had lower SIRT1 and higher HIF-1α amounts in kidney specimens in comparison with non-diabetic mice, and TSWN promoted SIRT1 and inhibited HIF-1α in the diabetic mouse kidney. Moreover, co-staining of SIRT1 and podocin revealed that SIRT1 decreased in podocytes from diabetic mice in comparison with those from non-diabetic mice, and TSWN elevated SIRT1 in podocytes.ConclusionsThis study indicated that TSWN alleviates DN by improving podocyte injury through the SIRT1/HIF-1α pathway in diabetic mouse kidneys.
High-Temperature Characterization of Melted Nuclear Core Materials: Investigating Corium Properties Through the Case Studies of In-Vessel and Ex-Vessel Retention
Authors: Delacroix Jules , Journeau Christophe , Piluso Pascal 
Published: June 2022

During a severe accident in a nuclear reactor, the molten core—or corium—may be relocated into the reactor vessel’s lower plenum in case of core support plate failure. The severe accident management strategy for In-Vessel Retention—or IVR—consists in stabilizing the corium within the reactor pressure vessel by external cooling of the vessel’s lower head. If now, the vessel fails due to excessive thermal loading on its walls, the Ex-Vessel Retention—or EVR—strategy is adopted. In this case, the core melt stabilization can be achieved by effective corium spreading, either in the reactor vessel cavity or in a dedicated “core-catcher”, and cooling by water. The success of both strategies highly depends on the corium behavior at high temperatures, conditioning vessel’s integrity for IVR, and promotion for the spreading of the EVR. This involves a variety of fundamental mechanisms closely related to heat and mass transfer regimes prevailing at the system scale, which requires further analytical and experimental insight to determine the primary mechanisms and feed the modeling tools, allowing the numerical simulations of severe accident scenarios.Within the framework of corium characterization at high temperatures, the present study aims at filling the lack of such fundamental data as density, surface tension, liquidus and solidus temperatures, and viscosity. In order to accurately measure these properties at high temperatures, the VITI facility is designed with various configurations. Concerning IVR, the influence of density and surface tension is particularly highlighted through VITI-SD and VITI-MBP configurations, and practical applications of experimental results are finally discussed, in link with the focusing effect issue at the thin upper metallic layer of the corium pool. Concerning EVR, the properties of interest are solidus/liquidus temperature and dynamic viscosity, and typical experimental results obtained through VITI-VPA and VITI-GFL configurations are discussed in view of characterizing corium spreading.
Resistance Performance of a Ship in Model-Scaled Brash Ice Fields Using CFD and DEM Coupling Model
Authors: Xie Chang , Zhou Li , Wu Tiecheng , Liu Renwei , Zheng Sijie , Tsuprik Vladimir G. , Bekker Alexander 
Published: June 2022

The brash ice channel formed with icebreaker navigation is a normal working scenario for ice-going vessels. Therefore, it is necessary to study brash ice resistance in this condition. In this study, CFD and DEM coupling methods were adopted to investigate the resistance performance of a ship sailing in model-scaled brash ice fields, considering the collision force and friction resistance, among the brash ice, and the water resistance and hydrodynamic force of brash ice, which make up physical scenarios of navigation in the brash ice channel. To study the effect of aforementioned parameters on the average total resistance, the time step, iteration, and brash ice stiffness were analyzed; we found that a time step of 0.02 s, iteration of 10, and brash ice stiffness of 1000 N/m that showed better repeatability of the physical phenomenon, and it was used to reproduce working conditions created in the HSVA ice tank test. The error between the numerical simulation results and the test results is less than 5%, which shows the robustness of the present coupling strategy. Finally, the effects of ship–ice friction coefficient, ice thickness, ice shape, brash ice channel width, and ice concentration on the resistance of the ship were investigated and verified with the published results.
Bioremediation Potential of Plant-Bacterial Consortia for Chlorpyrifos Removal Using Constructed Wetland
Authors: Aziz Tahira , Rasheed Sajida , Shah Asad Hussain , Nasir Habib , Fariq Anila , Jamil Asma , Jannat Sammyia 
Published: June 2022

The extensive and unchecked application of chlorpyrifos against crop insects has caused contamination of various ecosystems, such as soil, sediments, and water, posing harm to plants, animals, useful arthropods, and humans. The present study aimed at evaluating the ability of proto-type constructed wetland to biodegrade chlorpyrifos and its major metabolites especially 2-hydroxy-3, 5, 6-trichloropyridine/ol (TCP) using chlorpyrifos-degrading indigenous bacterial strains, namely, Acinetobacter baumanni and Bacillus cibi with Canna spps. and indigenous Mentha spps. as a bacterial–plant consortium. Soil and plant samples were collected at regular time intervals for 12 weeks; analytes were extracted using the toluene method and evaluated through gas chromatography–mass spectrometry (GC-MS). In case of wetland vegetation with Canna and Mentha, 2-hydroxy-3, 5, 6-trichloropyridine (TCP, m/z = 198) and 2- hydroxypyridine (m/z = 97) with deprotonated molecular ions at m/z = 69 (M-H)−were detected as the intermediate metabolites, while in the bacterial–plant consortium, instead of TCP, 3, 5, 6-trichloro-2-methoxypyridine (TMP, m/z = 212) was formed along with di-ethylthiophosphate (DETP, m/z = 169). Based on the metabolite analysis using GC-MS, the biodegradation pathway for chlorpyrifos degradation through bacterial–plant consortia is predicted. The constructed wetland with the bacterial–plant consortium showed its potential to either bypass TCP generation, or TCP may have been immediately biodegraded by the plant part of the consortium. The designed constructed wetland provided a novel remedial measure to biodegrade chlorpyrifos without producing harmful metabolites.
Client Experiences in a Mobile-Phone Counseling Intervention for Enhancing Access to Prevention of Mother To-Child Transmission (PMTCT) Services in Kenya
Authors: Okal Jerry Okoth , Sarna Avina , Lango Daniel , Matheka James , Owuor Danmark , Kinywa Eunice Auma , Kalibala Sam 
Published: June 2022

BackgroundThe prevention of mother-to-child transmission (PMTCT) is considered one of the most successful HIV prevention strategies in detecting and reducing HIV acquisition in utero or at birth. It is anticipated that with the increasing growth of digital technologies mobile phones can be utilized to enhance PMTCT services by improving provider-client interactions, expanding access to counseling services, and assisting in counteracting social and structural barriers to uptake of PMTCT services. Understanding the subjective experiences of women accessing PMTCT services in different settings has the potential to inform the development and promotion of such methods. This paper explores the perspectives of HIV-positive pregnant women attending maternal and neonatal clinic services in Kisumu, Kenya.MethodsData are reported from in-depth interviews with women, following a longitudinal study investigating the impact of a structured, counselor-delivered, mobile phone counseling intervention to promote retention in care and adherence to ARV prophylaxis/treatment, for HIV-positive pregnant women. Thematic content analysis was conducted.ResultsDiscussions indicated that mobile-phone counseling provided useful health-related information, enhanced agency, and assisted mothers access critical PMTCT services across the cascade of care. Similarly, mobile-phone counseling offered personalized one-to-one contact with trained health providers including facilitating discussion of personal issues that likely affect access to services. Findings also identified barriers to the uptake of services, including a lack of partner support, poor health, poverty, facility-related factors, and provider attitudes.DiscussionOverall, findings show that mobile-phone counseling is feasible, acceptable, and can enhance access to PMTCT services by overcoming some of the individual and facility-level barriers. Although mobile-phone counseling has not been routinized in most health facilities, future work is needed to assess whether mobile-phone counseling can be scaled-up to aid in the effective use of HIV and PMTCT services, as well as improving other related outcomes for mother and child dyad.
Granulocyte-Macrophage Colony-Stimulating Factor Modulates Myeloid-Derived Suppressor Cells and Treg Activity in Decompensated Cirrhotic Patients With Sepsis
Authors: Sehgal Rashi , Maiwall Rakhi , Rajan Vijayaraghavan , Islam Mojahidul , Baweja Sukriti , Kaur Navkiran , Kumar Guresh , Ramakrishna Gayatri , Sarin Shiv K. , Trehanpati Nirupma 
Published: June 2022

BackgroundDecompensated cirrhosis patients are more prone to bacterial infections. Myeloid-derived suppressor cells (MDSCs) expand in sepsis patients and disrupt immune cell functions. Granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy helps in restoring immune cell functions and resolving infections. Its role in MDSC modulation in cirrhosis with sepsis is not well understood.MethodsA total of 164 decompensated cirrhotic—62 without (w/o), 72 with sepsis, and 30 with sepsis treated with GM-CSF—and 15 healthy were studied. High-dimensional flow cytometry was performed to analyze MDSCs, monocytes, neutrophils, CD4 T cells, and Tregs at admission and on days 3 and day 7. Ex vivo co-cultured MDSCs with T cells were assessed for proliferation and apoptosis of T cells and differentiation to Tregs. Plasma factors and mRNA levels were analyzed by cytokine-bead assay and qRT-PCR.ResultsFrequencies of MDSCs and Tregs were significantly increased (p = 0.011 and p = 0.02) with decreased CD4 T cells (p = 0.01) in sepsis than w/o sepsis and healthy controls (HCs) (p = 0.000, p = 0.07, and p = 0.01) at day 0 and day 7. In sepsis patients, MDSCs had increased IL-10, Arg1, and iNOS mRNA levels (p = 0.016, p = 0.043, and p = 0.045). Ex vivo co-cultured MDSCs with T cells drove T-cell apoptosis (p = 0.03, p = 0.03) with decreased T-cell proliferation and enhanced FOXP3+ expression (p = 0.044 and p = 0.043) in sepsis compared to w/o sepsis at day 0. Moreover, blocking the MDSCs with inhibitors suppressed FOXP3 expression. GM-CSF treatment in sepsis patients significantly decreased MDSCs and FOXP3+ Tregs but increased CD4 T-cell functionality and improved survival.ConclusionMDSCs have an immunosuppressive function by expanding FOXP3+ Tregs and inhibiting CD4+ T-cell proliferation in sepsis. GM-CSF treatment suppressed MDSCs, improved T-cell functionality, and reduced Tregs in circulation.
Bioenergetic Failure Drives Functional Exhaustion of Monocytes in Acute-on-Chronic Liver Failure
Authors: Maheshwari Deepanshu , Kumar Dhananjay , Jagdish Rakesh Kumar , Nautiyal Nidhi , Hidam Ashinikumar , Kumari Rekha , Sehgal Rashi , Trehanpati Nirupama , Baweja Sukriti , Kumar Guresh , Sinha Swati , Bajpai Meenu , Pamecha Viniyendra , Bihari Chhagan , Maiwall Rakhi , Sarin Shiv Kumar , Kumar Anupam 
Published: June 2022

ObjectiveThe monocyte–macrophage system is central to the host’s innate immune defense and in resolving injury. It is reported to be dysfunctional in acute-on-chronic liver failure (ACLF). The disease-associated alterations in ACLF monocytes are not fully understood. We investigated the mechanism of monocytes’ functional exhaustion and the role of umbilical cord mesenchymal stem cells (ucMSCs) in re-energizing monocytes in ACLF.DesignMonocytes were isolated from the peripheral blood of ACLF patients (n = 34) and matched healthy controls (n = 7) and patients with compensated cirrhosis (n = 7); phagocytic function, oxidative burst, and bioenergetics were analyzed. In the ACLF mouse model, ucMSCs were infused intravenously, and animals were sacrificed at 24 h and day 11 to assess changes in monocyte function, liver injury, and regeneration.ResultsPatients with ACLF (alcohol 64%) compared with healthy controls and those with compensated cirrhosis had an increased number of peripheral blood monocytes (p &lt; 0.0001) which displayed significant defects in phagocytic (p &lt; 0.0001) and oxidative burst capacity (p &lt; 0.0001). ACLF patients also showed a significant increase in the number of liver macrophages as compared with healthy controls (p &lt; 0.001). Bioenergetic analysis showed markedly reduced oxidative phosphorylation (p &lt; 0.0001) and glycolysis (p &lt; 0.001) in ACLF monocytes. Patients with monocytes having maximum mitochondrial respiration of &lt;37.9 pmol/min [AUC = 0.822, hazard ratio (HR) = 4.5] and baseline glycolysis of ≤42.7 mpH/min (AUC = 0.901, HR = 9.1) showed increased 28-day mortality (p &lt; 0.001). Co-culturing ACLF monocytes with ucMSC showed improved mitochondrial respiration (p &lt; 0.01) and phagocytosis (p &lt; 0.0001). Furthermore, ucMSC therapy increased monocyte energy (p &lt; 0.01) and phagocytosis (p &lt; 0.001), reduced hepatic injury, and enhanced hepatocyte regeneration in ACLF animals.ConclusionBioenergetic failure drives the functional exhaustion of monocytes in ACLF. ucMSCs resuscitate monocyte energy and prevent its exhaustion. Restoring monocyte function can ameliorate hepatic injury and promote liver regeneration in the animal model of ACLF.
Impact of Diminished Expression of circRNA on Multiple Sclerosis Pathomechanisms
Authors: Mycko Marcin P. , Zurawska Anna E. , Selmaj Igor , Selmaj Krzysztof W. 
Published: June 2022

Circular RNA (circRNA) molecules represent a novel and unique class of endogenous non-coding RNAs controlling the expression and function of microRNA (miRNA) and post-transcriptional regulation. Recent studies implicated circRNA in the pathomechanism of multiple sclerosis (MS). Hybridization microarray was used to define the circRNA profile in the peripheral blood mononuclear cells (PBMCs) from 20 untreated patients with relapsing–remitting MS (RRMS: 10 in relapse, 10 in remission) and 10 healthy controls (HCs). We analyzed close to 14,000 individual circRNAs per sample. The discovery set data were validated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) with an independent cohort of 45 RRMS patients (18 in relapse, 27 in remission) and 27 HCs. Microarray analysis revealed 246 circRNAs differentially downregulated (P &lt; 0.05) in RRMS patients versus HCs. We validated two circRNAs of the three showing the lowest levels of differential expression in the RRMS remission group versus the HC group: hsa_circRNA_101145 and hsa_circRNA_001896. Their expression was significantly decreased during remission in RRMS (P = 0.0000332, FC = 0.385 and P = 0.0455, FC = 0.591, respectively) and in patients showing a lower level of disability (hsa_circRNA_101145, P = 0.0695; hsa_circRNA_001896, P = 0.0008). Bioinformatic analysis revealed 10 miRNAs interacting with these circRNAs in a complementary manner and led to the discovery of three protein-coding mRNAs downregulated in patients with RRMS during remission. These transcripts have been previously implicated in oxidative stress, blood–brain barrier permeability, microglia function, and extracellular matrix molecules altering the microenvironment and inhibiting oligodendrocyte progenitor cells. circRNAs displayed a distinct profile in PBMCs from patients with RRMS, and our results may implicate circRNAs with low expression in important mechanistic pathways of RRMS.
Single-Cell RNA and ATAC Sequencing Reveal Hemodialysis-Related Immune Dysregulation of Circulating Immune Cell Subpopulations
Authors: Wu Hongwei , Dong Jingjing , Yu Haiyan , Wang Kang , Dai Weier , Zhang Xinzhou , Hu Nan , Yin Lianghong , Tang Donge , Liu Fanna , Dai Yong 
Published: June 2022

BackgroundAn increased risk of infection, malignancy, and cardiovascular diseases in maintenance hemodialysis patients is associated with hemodialysis-related immunity disturbances. Although defects in T-lymphocyte-dependent immune responses and preactivation of antigen-presenting cells have been documented in hemodialysis patients, the effects of long-term hemodialysis on the transcriptional program and chromosomal accessibility of circulating immune cell subpopulations remain poorly defined.MethodsWe integrated single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) to characterize the transcriptome profiles of peripheral mononuclear cells (PBMCs) from healthy controls and maintenance hemodialysis patients. Validation of differentially expressed genes in CD4+ T cells and monocytes were performed by magnetic bead separation and quantitative real-time PCR.ResultsWe identified 16 and 15 PBMC subgroups in scRNA-seq and scATAC-seq datasets, respectively. Hemodialysis significantly suppressed the expression levels of T cell receptor (TCR) genes in CD4+ T cell subsets (e.g., TRAV4, CD45, CD3G, CD3D, CD3E) and major histocompatibility complex II (MHC-II) pathway-related genes in monocytes (HLA-DRB1, HLA-DQA2, HLA-DQA1, HLA-DPB1). Downstream pathways of TCR signaling, including PI3K-Akt-mTOR, MAPK, TNF, and NF-κB pathways, were also inhibited in CD4+ T cell subpopulations during the hemodialysis procedure. Hemodialysis altered cellular communication patterns between PBMC subgroups, particularly TGF-TGFBR, HVEM-BTLA, and IL16-CD4 signalings between CD4+ T cells and monocytes. Additionally, we found that hemodialysis inhibited the expression of AP-1 family transcription factors (JUN, JUND, FOS, FOSB) by interfering with the chromatin accessibility profile.ConclusionsOur study provides a valuable framework for future investigations of hemodialysis-related immune dysregulation and identifies potential therapeutic targets for reconstituting the circulating immune system in maintenance hemodialysis patients.