Objective: Hepatocellular carcinoma (HCC) is a genetically and phenotypically heterogeneous tumor, and the prediction of its prognosis remains a challenge. In the past decade, studies elucidating the mechanisms that induce tumor cell pyroptosis has rapidly increased. The elucidation of their mechanisms is essential for the clinical development optimal application of anti-hepatocellular carcinoma therapeutics.Methods: Based on the different expression profiles of pyroptosis-related genes in HCC, we constructed a LASSO Cox regression pyroptosis-related genes signature that could more accurately predict the prognosis of HCC patients.Results: We identified seven pyroptosis-related genes signature (BAK1, CHMP4B, GSDMC, NLRP6, NOD2, PLCG1, SCAF11) in predicting the prognosis of HCC patients. Kaplan Meier survival analysis showed that the pyroptosis-related high-risk gene signature was associated with poor prognosis HCC patients. Moreover, the pyroptosis-related genes signature performed well in the survival analysis and ICGC validation group. The hybrid nomogram and calibration curve further demonstrated their feasibility and accuracy for predicting the prognosis of HCC patients. Meanwhile, the evaluation revealed that our novel signature predicted the prognosis of HCC patients more accurately than traditional clinicopathological features. GSEA analysis further revealed the novel signature associated mechanisms of immunity response in high-risk groups. Moreover, analysis of immune cell subsets with relevant functions revealed significant differences in aDCs, APC co-stimulation, CCR, check-point, iDCs, Macrophages, MHC class-I, Treg, and type II INF response between high- and low-risk groups. Finally, the expression of Immune checkpoints was enhanced in high-risk group, and m6A-related modifications were expressed differently between low- and high-risk groups.Conclusion: The novel pyroptosis-related genes signature can predict the prognosis of patients with HCC and insight into new cell death targeted therapies.
Objective. To investigate the potential active ingredients and underlying mechanisms of Artemisia annua (AA) on the treatment of hepatocellular carcinoma (HCC) based on network pharmacology. Methods. In the present study, we used a network pharmacological method to predict its underlying complex mechanism of treating HCC. First, we obtained relative compounds of AA based on the traditional Chinese medicine systems pharmacology (TCMSP) database and collected potential targets of these compounds by target fishing. Then, we built HCC-related targets target by the oncogenomic database of hepatocellular carcinoma (OncoDB.HCC) and biopharmacological network (PharmDB-K) database. Based on the matching results between AA potential targets and HCC targets, we built a protein-protein interaction (PPI) network to analyze the interactions among these targets and screen the hub targets by topology. Furthermore, the function annotation and signaling pathways of key targets were performed by Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis using DAVID tools. Finally, the binding capacity between active ingredients and key targets was validated by molecular docking. Results. A total of 19 main active ingredients of AA were screened as target prediction; then, 25 HCC-related common targets were seeked out via multiple HCC databases. The areas of nodes and corresponding degree values of EGFR, ESR1, CCND1, MYC, EGF, and PTGS2 were larger and could be easily found in the PPI network. Furthermore, GO and KEGG enrichment analysis showed that these key targets were significantly involved in multiple biological processes and pathways which participated in tumor cell proliferation, apoptosis, angiogenesis, tumor invasion, and metastasis to accomplish the anti-HCC activity. The molecular docking analysis showed that quercetin could stably bind to the active pocket of EGFR protein 4RJ5 via LibDock. Conclusion. The anticancer effects of AA on HCC were predicted to be associated with regulating tumor cell proliferation, apoptosis, angiogenesis, tumor invasion, and metastasis via various pathways such as the EGFR signaling pathway, ESR1 signaling pathway, and CCND1 signaling pathway. It is suggested that AA might be developed as a broad-spectrum antitumor drug based on its characteristics of multicomponent, multipath, and multitarget.
The timely and accurate mapping of the spatial distribution of grasslands is crucial for maintaining grassland habitats and ensuring the sustainable utilization of resources. We used Google Earth Engine (GEE) and Sentinel-2 data for mountain grassland extraction in Yunnan, China. The differences in the normalized vegetation index in the time-series data of different ground objects were compared. February to March, during grassland senescence, was the optimum phenological stage for grassland extraction. The spectral, textural of Sentinel-2, and topographic features of the Shuttle Radar Topography Mission (SRTM) were used for the classification. The features were optimized using the recursive feature elimination (RFE) feature importance selection algorithm. The overall accuracy of the random forest (RF) classification algorithm was 91.2%, the producer’s accuracy of grassland was 96.7%, and the user’s accuracy of grassland was 89.4%, exceeding that of the cart classification (Cart), support vector machine (SVM), and minimum distance classification (MDC). The SWIR1 and elevation were the most important features. The results show that Yunnan has abundant grassland resources, accounting for 18.99% of the land area; most grasslands are located in the northwest at altitudes above 3200 m and in the Yuanjiang River regions. This study provides a new approach for feature optimization and grassland extraction in mountainous areas, as well as essential data for the further investigation, evaluation, protection, and utilization of grassland resources.
Ultrafast electron diffraction and time-resolved serial crystallography are the basis of the ongoing revolution in capturing at the atomic level of detail the structural dynamics of molecules. However, most experiments capture only the probability density of the nuclear wavepackets to determine the time-dependent molecular structures, while the full quantum state has not been accessed. Here, we introduce a framework for the preparation and ultrafast coherent diffraction from rotational wave packets of molecules, and we establish a new variant of quantum state tomography for ultrafast electron diffraction to characterize the molecular quantum states. The ability to reconstruct the density matrix, which encodes the amplitude and phase of the wavepacket, for molecules of arbitrary degrees of freedom, will enable the reconstruction of a quantum molecular movie from experimental x-ray or electron diffraction data.
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