Detailed Mitochondrial Phenotyping by High Resolution Metabolomics

Mitochondrial phenotype is complex and difficult to define at the level of individual cell types. Newer metabolic profiling methods provide information on dozens of metabolic pathways from a relatively small sample. This pilot study used “top-down” metabolic profiling to determine the spectrum of metabolites present in liver mitochondria. High resolution mass spectral analyses and multivariate statistical tests provided global metabolic information about mitochondria and showed that liver mitochondria possess a significant phenotype based on gender and genotype. The data also show that mitochondria contain a large number of unidentified chemicals

A Novel MBAS-RF Approach to Predict Mechanical Properties of Geopolymer-Based Compositions

Using gels to replace a certain amount of cement in concrete is conducive to the green concrete industry, while testing the compressive strength (CS) of geopolymer concrete requires a substantial amount of substantial effort and expense. To solve the above issue, a hybrid machine learning model of a modified beetle antennae search (MBAS) algorithm and random forest (RF) algorithm was developed in this study to model the CS of geopolymer concrete, in which MBAS was employed to adjust the hyperparameters of the RF model. The performance of the MBAS was verified by the relationship between 10-fold cross-validation (10-fold CV) and root mean square error (RMSE) value, and the prediction performance of the MBAS and RF hybrid machine learning model was verified by evaluating the correlation coefficient (R) and RMSE values and comparing with other models. The results show that the MBAS can effectively tune the performance of the RF model; the hybrid machine learning model had high R values (training set R = 0.9162 and test set R = 0.9071) and low RMSE values (training set RMSE = 7.111 and test set RMSE = 7.4345) at the same time, which indicated that the prediction accuracy was high; NaOH molarity was confirmed as the most important parameter regarding the CS of geopolymer concrete, with the importance score of 3.7848, and grade 4/10 mm was confirmed as the least important parameter, with the importance score of 0.5667

Experimental Study of the Microstructural Evolution of Glauberite and Its Weakening Mechanism under the Effect of Thermal-Hydrological-Chemical Coupling

The microstructures of rock gradually evolve with changes in the external environment. This study focused on the microstructure evolution of glauberite and its weakening mechanism under different leaching conditions. The porosity were used as a characteristic index to study the effect of brine temperature and concentration on crack initiation and propagation in glauberite. The research subjects were specimens of ϕ3 × 10 mm cylindrical glauberite core, obtained from a bedded salt deposit buried more than 1000 m underground in the Yunying salt formation, China. The results showed that when the specimens were immersed in solution at low temperature, due to hydration impurities, cracks appeared spontaneously at the centre of the disc and the solution then penetrated the specimens via these cracks and dissolved the minerals around the crack lines. However, with an increase of temperature, the dissolution rate increased greatly, and crack nucleation and dissolved regions appeared simultaneously. When the specimens were immersed in a sodium chloride solution at the same concentration, the porosity s presented gradual upward trends with a rise in temperature, whereas, when the specimens were immersed in the sodium chloride solution at the same temperature, the porosity tended to decrease with the increase of sodium chloride concentration. In the process of leaching, the hydration of illite, montmorillonite, and the residual skeleton of glauberite led to the expansion of the specimen volume, thereby producing the cracks. The diameter expansion rate and the expansion velocity of the specimen increased with temperature increase, whereas, due to the common-ion effect, the porosity of the specimen decreases with the increase of sodium chloride solution concentration

Comprehensive analysis of glycoprotein VI-mediated platelet activation signaling pathway for predicting pan-cancer survival and response to anti-PD-1 immunotherapy

Platelets play a vital role in cancer and immunity. However, few comprehensive studies have been conducted on the role of platelet-related signaling pathways in various cancers and their responses to immune checkpoint blockade (ICB) therapy. In the present study, we focused on the glycoprotein VI-mediated platelet activation (GMPA) signaling pathway and comprehensively evaluated its roles in 19 types of cancers listed in The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Cox regression and meta-analyses showed that for all 19 types of cancers, patients with high GMPA scores tended to have a good prognosis. Furthermore, the GMPA signature score could serve as an independent prognostic factor for patients with skin cutaneous melanoma (SKCM). The GMPA signature was linked to tumor immunity in all 19 types of cancers, and was correlated with SKCM tumor histology. Compared to other signature scores, the GMPA signature scores for on-treatment samples were more robust predictors of the response to anti-PD-1 blockade in metastatic melanoma. Moreover, the GMPA signature scores were significantly negatively correlated with EMMPRIN (CD147) and positively correlated with CD40LG expression at the transcriptomic level in most cancer patient samples from the TCGA cohort and on-treatment samples from anti-PD1 therapy cohorts. The results of this study provide an important theoretical basis for the use of GMPA signatures, as well as GPVI-EMMPRIN and GPVI-CD40LG pathways, to predict the responses of cancer patients to various types of ICB therapy

Functional Gene Expression Signatures from On-Treatment Tumor Specimens Predict Anti-PD1 Blockade Response in Metastatic Melanoma

Functional gene expression signatures (FGES) from pretreatment biopsy samples have been used to predict the responses of metastatic melanoma to immune checkpoint blockade (ICB) therapies. However, there are no predictive FGE signatures from patients receiving treatment. Here, using the Elastic Net Regression (ENLR) algorithm, we analyzed transcriptomic and matching clinical data from a dataset of patients with metastatic melanoma treated with ICB therapies and produced an FGE signature for pretreatment (FGES-PRE) and on-treatment (FGES-ON). Both the FGES-PRE and FGES-ON signatures are validated in three independent datasets of metastatic melanoma as the validation set, achieving area under the curve (AUC) values of 0.44–0.81 and 0.82–0.83, respectively. Then, we combined all test samples and obtained AUCs of 0.71 and 0.82 for the FGES-PRE and FGES-ON signatures, respectively. The FGES-ON signatures had a higher predictive value for prognosis than the FGES-PRE signatures. The FGES-PRE and FGES-ON signatures were divided into high- and low-risk scores using the signature score mean value. Patients with a high FGE signature score had better survival outcomes than those with low scores. Overall, we determined that the FGES-ON signature is an effective biomarker for metastatic melanoma patients receiving ICB therapy. This work would provide an important theoretical basis for applying FGE signatures derived from on-treatment tumor samples to predict patients’ therapeutic response to ICB therapies

Effects of tectonic stresses and structural planes on slope deformation and stability at the Buzhaoba open pit mine, China

Tectonic stresses and structural planes are key factors that affect slope stability. The studies of the effect mechanism of the two factors on the slope deformation and instability have an important value for realizing an accurate evaluation of slope stability. The deformation and landslide problems of the west slope at the Buzhaoba open pit mine were analyzed. Tectonic stresses and structural planes were confirmed as the main factors of long-term deformation of the slope. According to an analysis of the regional structure, the principal stress direction of the Buzhaoba mine was 123° and the slope sliding mode and discriminant conditions were determined under the influence of tectonic stress. The principal stress direction was verified by comparison with the results of displacement monitoring and stability analysis of the slope. The factor of safety of the slope is 1.29 when considering tectonic stress and reduces by 7.19% when tectonic stress is not considered