Crohn's disease (CD) is a type of heterogeneous, dysfunctional immune-mediated intestinal chronic and recurrent inflammation caused by a variety of etiologies. Cuproptosis is a newly discovered form ...of programmed cell death that seems to contribute to the advancement of a variety of illnesses. Consequently, the major purpose of our research was to examine the role of cuproptosis-related genes in CD.
We obtained two CD datasets from the gene expression omnibus (GEO) database, and immune cell infiltration was created to investigate immune cell dysregulation in CD. Based on differentially expressed genes (DEGs) and the cuproptosis gene set, differentially expressed genes of cuproptosis (CuDEGs) were found. Then, candidate hub cuproptosis-associated genes were found using machine learning methods. Subsequently, using 437 CD samples, we explored two distinct subclusters based on hub cuproptosis-related genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, Gene set variation analysis (GSVA) and immune infiltration analysis studies were also used to assess the distinct roles of the subclusters.
Overall, 25 CuDEGs were identified, including ABCB6, BACE1, FDX1, GLS, LIAS, MT1M, PDHA1, etc. And most CuDEGs were expressed at lower levels in CD samples and were negatively related to immune cell infiltration. Through the machine learning algorithms, a seven gene cuproptosis-signature was identified and two cuproptosis-related subclusters were defined. Cluster-specific differentially expressed genes were found only in one cluster, and functional analysis revealed that they were involved in several immune response processes. And the results of GSVA showed positive significant enrichment in immune-related pathways in cluster A, while positive significant enrichment in metabolic pathways in cluster B. In addition, an immune infiltration study indicated substantial variation in immunity across different groups. Immunological scores were higher and immune infiltration was more prevalent in Cluster A.
According to the current research, the cuproptosis phenomenon occurs in CD and is correlated with immune cell infiltration and metabolic activity. This information indicates that cuproptosis may promote CD progression by inducing immunological response and metabolic dysfunction. This research has opened new avenues for investigating the causes of CD and developing potential therapeutic targets for the disease.
Cellular diversity of the lung endothelium has not been systematically characterized in humans. We provide a reference atlas of human lung endothelial cells (ECs) to facilitate a better understanding ...of the phenotypic diversity and composition of cells comprising the lung endothelium.
We reprocessed human control single-cell RNA sequencing (scRNAseq) data from 6 datasets. EC populations were characterized through iterative clustering with subsequent differential expression analysis. Marker genes were validated by fluorescent microscopy and in situ hybridization. scRNAseq of primary lung ECs cultured in vitro was performed. The signaling network between different lung cell types was studied. For cross-species analysis or disease relevance, we applied the same methods to scRNAseq data obtained from mouse lungs or from human lungs with pulmonary hypertension.
Six lung scRNAseq datasets were reanalyzed and annotated to identify >15 000 vascular EC cells from 73 individuals. Differential expression analysis of EC revealed signatures corresponding to endothelial lineage, including panendothelial, panvascular, and subpopulation-specific marker gene sets. Beyond the broad cellular categories of lymphatic, capillary, arterial, and venous ECs, we found previously indistinguishable subpopulations; among venous EC, we identified 2 previously indistinguishable populations: pulmonary-venous ECs (COL15A1
) localized to the lung parenchyma and systemic-venous ECs (COL15A1
) localized to the airways and the visceral pleura; among capillary ECs, we confirmed their subclassification into recently discovered aerocytes characterized by
,
, and
and general capillary EC. We confirmed that all 6 endothelial cell types, including the systemic-venous ECs and aerocytes, are present in mice and identified endothelial marker genes conserved in humans and mice. Ligand-receptor connectome analysis revealed important homeostatic crosstalk of EC with other lung resident cell types. scRNAseq of commercially available primary lung ECs demonstrated a loss of their native lung phenotype in culture. scRNAseq revealed that endothelial diversity is maintained in pulmonary hypertension. Our article is accompanied by an online data mining tool (www.LungEndothelialCellAtlas.com).
Our integrated analysis provides a comprehensive and well-crafted reference atlas of ECs in the normal lung and confirms and describes in detail previously unrecognized endothelial populations across a large number of humans and mice.
Traditional architectural elements carry our excellent traditional culture, contain rich connotation, and are the valuable wealth of modern architectural environment design research and reference. ...However, the application of traditional architectural elements in the architectural environment design has some problems, such as homogenization and does not reflect the connotation of traditional architectural elements. The effective integration of traditional architectural elements and architectural environment design is of great significance to the development, inheritance of traditional architectural elements and the development of architectural environment design engineering. On the basis of understanding the design characteristics of the architectural environment art, this paper analyzes the current situation of the traditional architectural elements in the architectural environment design, and puts forward the countermeasures to effectively integrate the traditional architectural elements and the architectural environment design. In order to combine the traditional architectural elements with the development needs and use functions of architectural environment design in the new era, enrich the connotation of architecture and improve the artistic aesthetic level of architectural environment design.
The great Wenchuan Earthquake occurred on May 12, 2008 in the Sichuan Province of China, and had a magnitude of 8.0. It is the most serious earthquake disaster in China since the great Tangshan ...Earthquake (
M
s
=7.8, July 28, 1976). According to official reports, there were 69,225 deaths, 379,640 injuries and 17,939 missing as of Aug. 11, 2008. The China Earthquake Administration quickly sent hundreds of experts to the field immediately after the event, to investigate the damage and assess the economic losses. This paper emphasizes the impact of seismic intensity and presents a preliminary loss assessment. A brief description of the geological features of the affected region is provided, followed by a summary of the earthquake damage. An isoseismal map is developed that shows that the high intensity region is distributed like a belt around the seimogenic fault, and that the epicentral intensity reached XI (Chinese Intensity Scale, similar to the Modified Mercalli Scale). The direct economic loss resulting from the earthquake is 692 billions RMB (about 100 billions US$).
In this contribution, we conduct a multi-angular analysis of the interdisciplinarity of Nobel Prize winning research compared to non-Nobel Prize winning articles, based on a large data set. Here ...interdisciplinarity is measured by the diversity of references, using two true diversity indicators. Articles mentioned by the Nobel Prize committee in Physiology or Medicine (in short: NP articles) awarded during the period from 1900 to 2016 are the focus of our research. These articles are compared with those in a dataset of articles that do not include a Nobel Prize winner among their authors. Moreover, these non-NPs articles were not only published in the same year and in the same research field as the NP ones but were also dealing with the same research topic (such articles are referred to as non-NP articles). The results suggest that the topic-related knowledge included in Nobel Prize winning work is higher than that in non-NPs, hence with lower interdisciplinarity than the latter. Our findings provide useful clues to better understand the characteristics of transformative research, here represented by key publications by Nobel Prize laureates in Physiology or Medicine, and their pattern of knowledge integration.
Corncob has a high yield and contains a large number of cellulose substances. Wet phosphoric acid hydrolysis of corncob is of great significance to the utilization of organic waste, and provides ...theoretical support for the development of sugar-containing synergistic phosphorus fertilizers. In this study, the kinetics of hydrolysis of corncob by wet process phosphoric acid was investigated. The time evolution of total sugar, xylose and furfural formation during a 12-h hydrolysis was simulated by Saeman and biphasic models within differential acid concentrations and temperatures. The formations of both total sugar and furfural coincide a first-order irreversible reaction, which was not applicable to the Saeman model nor the biphasic model. Meanwhile, xylose formation was more suitable for the Saeman model. The optimal conditions for xylose are: a temperature of 100 °C, a reaction time of 720 min, an acid concentration of 55.6% (w/w). The xylose yield of corncobs was 0.15 g/g in the optimal conditions.
Graphical abstract
Diseases in pulmonary vasculature remain a major cause of morbidity and mortality worldwide. Numerous pre-clinical animal models were developed to understand lung vasculature during diseases and ...development. However, these systems are typically limited in their ability to represent human pathophysiology for the study of disease and drug mechanisms. In recent years, a growing number of studies have focused on developing in vitro experimental platforms that mimic human tissues/organs. In this chapter, we discuss the key components involved in developing engineered pulmonary vascular modeling systems and provide perspectives on ways to improve the translational potential of existing models.
INTRODUCTION
Because growing interest has been focusing on cerebral blood flow (CBF) to predict, prevent, and treat Alzheimer's disease (AD), it is important to clarify the role of CBF in AD ...pathology and cognitive decline.
METHODS
In a moyamoya disease (MMD) cohort, we examined CBF, specific cognitive domains, and plasma AD biomarkers, as well as correlations among these variables.
RESULTS
CBF was significantly reduced in newly diagnosed MMD patients, while plasma phosphorylated tau181 was elevated and positively correlated with hypoperfusion accumulation. MMD patients scored significantly lower than controls in multiple cognitive tests. Revascularization increased CBF to the recipient brain territories as well as cognitive performance but produced no significant change in AD biomarker levels.
DISCUSSION
These data suggest a link between accumulated reductions in CBF and cognitive decline, as well as a possible role of AD‐like pathological burden. Further studies in MMD will provide opportunities to explore new treatment strategies.
Efforts to decipher chronic lung disease and to reconstitute functional lung tissue through regenerative medicine have been hampered by an incomplete understanding of cell-cell interactions governing ...tissue homeostasis. Because the structure of mammalian lungs is highly conserved at the histologic level, we hypothesized that there are evolutionarily conserved homeostatic mechanisms that keep the fine architecture of the lung in balance. We have leveraged single-cell RNA sequencing techniques to identify conserved patterns of cell-cell cross-talk in adult mammalian lungs, analyzing mouse, rat, pig, and human pulmonary tissues. Specific stereotyped functional roles for each cell type in the distal lung are observed, with alveolar type I cells having a major role in the regulation of tissue homeostasis. This paper provides a systems-level portrait of signaling between alveolar cell populations. These methods may be applicable to other organs, providing a roadmap for identifying key pathways governing pathophysiology and informing regenerative efforts.
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