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Background: In the realm of tumor-targeted therapeutics, Polo-like kinases (PLKs) are a significant group of protein kinases that were found recently as being related to tumors. However, the significance of PLKs in pan-cancer remains systematically studied. Methods and materials: We integrated multi-omics data to comprehensively investigate the expression patterns of the PLK family across various cancer types. Subsequently, study examined the associations between tumor mutation burden (TMB), microsatellite instability (MSI), immune subtype classification, immune infiltration, tumor microenvironment scores, immune checkpoint gene expression, and the PLKs expression profiles within various tumor types. Furthermore, using our mRNA sequencing data (TRUCE01) and four bladder cancer (BLCA) cohorts (GSE111636, GSE176307, and IMvigor210), We examined the correlation between the expression level of PLK and immunotherapy effectiveness. Next, Gene set enrichment analysis (GSEA) was evaluated to find that potentially enriched PLK signaling pathways. Utilizing TIMER 2.0, we conducted an immune infiltration analysis underlying transcriptome expression, copy number variations (CNV), or somatic mutations of PLKs in BLCA. Finally, mRNA expression validation of PLK1/3/4 by real-time PCR within 10 paired BLCA tissues, protein expression verification through the Human Protein Atlas (HPA), and PLK4 in vitro cytological studies have been employed in BLCA. Results: The expression of most of the PLK family members exhibits variation between cancerous tissues and adjacent normal tissues across various cancer species. Furthermore, the expression of PLKs demonstrates a significant association with immunotyping, infiltration of immune cell, tumor mutational burden (TMB), microsatellite instability (MSI), immunological checkpoint gene activity and therapeutic effectiveness in pan-tumor tissues. Additional investigation into the correlation between the PLK family and BLCA has revealed that the expression of the PLK genes holds substantial significance in the biological processes of BLCA. Furthermore, a notable association has been observed between the copy number variation, variant status, and the degree of certain immunological cell infiltration. Of note, the expression validation and in vitro phenotypic experiments have demonstrated that PLK4 has a significant function in promoting the BLCA cell proliferation, migration, and invasion. Conclusion: Collectively, based on various databases, our results highlight the involvement of PLK gene family in the formation of different types of tumors and identify PLK-related genes that may be used for therapy.

Background: Danshen Ligustrazine Injection (DSLI), composed of the extract of Salvia miltiorrhiza Bunge and Conioselinum anthriscoides 'Chuanxiong', is commonly used in the clinical treatment of ischemic stroke, which is the most common type of cerebrovascular disease, affected by multiple factors. The brain-gut axis is a new type of influencing factor for ischemic stroke, however, there is a lack of systematic research on the relationship between microbiota and host metabolic phenotype. This study aimed to investigate the host metabolic phenotype-microbiome interface in ischemic stroke and the immunomodulatory effects of DSLI. Methods: In the study, liquid chromatography-mass spectrometry was used to primarily analyze the quality markers (Q-markers) and the polyphenols of DSLI. Based on 16S rRNA gene sequencing and metabolomics, the variations of microbial composition in different groups were characterized. In addition, a network diagram was constructed to reveal the interrelationship between DSLI-regulated gut microbiota changes and DSLI-regulated brain metabolites in MCAO/R rats. The expression of the aryl hydrocarbon receptor (AhR) in the colon and brain by immunofluorescence and suppressors of cytokine signaling 2 (SOCS2) by western blot were further detected. Results: Diminished metabolic diversity and alterations in the tryptophan metabolism pathway were a feature of IS in the study. The results revealed that Clostri_UCG-014 was positively correlated with indoleacrylic acid, indole-3-methylacetate, and Ruminococcaceae was strongly related with L-tryptophan, 3-methylindole, and indole. The results of immunofluorescence showed that the expression of AhR in the colon and brain tissues of rats in the model group was greatly reduced compared with that in the sham-operated group, and was heavily activated with the treatment of DSLI. The levels of aryl hydrocarbon nuclear receptor ARNT2 and SOCS2 were down-regulated in the brains of Model rats, whereas increased by DSLI, further confirming that the brain-gut microbiota-Trp metabolism exists in the pathological changes of stroke and the intervention mechanism of DSLI. Conclusions: The present study findings suggest Clostri_UCG-014, Ruminococcaceae, and Firmicute_RF39 play an important role in improving the regulation of immune function in stroke through tryptophan metabolites by acting on the AhR-SOCS2 axis.

Mailuoshutong pill (MLSTP) is a traditional Chinese medicine compound preparation used for the treatment of thromboangiitis obliterans. However, component responsible for those effects are not yet identified, nor with their accurate contents and in-vivo movement, which means the quality markers of MLSTP are still unknown. The aim of this study was to discovery quality markers of MLSTP by developing a new multi-dimensional network strategy based on “Content-Pharmacokinetics-Pharmacology”. 40 analytes were determined by UHPLC-MS/MS in 8 min and the average contents in 11 batches of commercial MLSTP samples were used as the content dimension, the pharmacokinetics and pharmacology dimension were evaluated by five variables based on ADME Prediction and Prediction of Activity Spectra. Each dimension of the characteristic network was quantified by multivariate statistical analysis, and a three-dimensional network was constructed. Finally, Liquiritin, Calycosin-7-glucoside and Albiflorin with larger regression area were preferred as quality markers of MLSTP, which had satisfactory comprehensive properties of content, pharmacokinetic properties and pharmacological activity. In summary, the potential quality markers of MLSTP were identified by multi-dimensional characteristic network of content, pharmacokinetics and pharmacology. Also, the new strategy established in this work provided a valuable perspective for the selection of quality control indicators from compound formula.

Water is the most critical resource that affects the stability of ecosystems and socio-economic development in arid and semi-arid regions. The rational development and utilization of water resources in Yinchuan Plain play a vital role in supporting and leading its ecological environment protection and high-quality agricultural development. Irrigation water from the Yellow River and groundwater are the main water resources of Yinchuan Plain. To understand the ecological impact of the Yellow River irrigation, the research analyzed the interaction between surface water and shallow groundwater using isotope hydrochemical method. The results show that both surface water and shallow groundwater are neutral and alkaline, the hydraulic relationships among the water bodies are strong. The correlation between 17O-excess and δ18O depends on the proportions of precipitation recharge and the intensity of evaporation. The chemical characteristics of water are controlled by evaporation, irrigation activities and water–rock interactions. Hydrochemical characteristics indicate that Yellow River irrigation has little impact on the Yellow River, but it has caused a rise in the groundwater level, intensified evaporation, and aggravated soil salinization. Isotopes indicate that Water-Saving Transformation Project has brought about a new ecological problem-lake shrinkage while reducing salinization. Therefore, we propose to moderately increase the amount of water diversion to flush the groundwater ions and extract the groundwater for human activities during the irrigation period to reduce salinization and water resource shortage. Salinization should be considered in relation to sustainable agricultural development and ecological environment health in Yinchuan Plain as well as other similar arid regions.