Facilitating integrative and personalized oncology omics analysis with UCSCXenaShiny.

The continuous generation of multi-omics and phenotype data is propelling advancements in precision oncology. UCSCXenaShiny was developed as an interactive tool for exploring thousands of cancer datasets available on UCSC Xena. However, its capacity for comprehensive and personalized pan-cancer data analysis is being challenged by the growing demands. Here, we introduce UCSCXenaShiny v2, a milestone update through a variety of improvements. Firstly, by integrating multidimensional data and implementing adaptable sample settings, we create a suite of robust TPC (TCGA, PCAWG, CCLE) analysis pipelines. These pipelines empower users to conduct in-depth analyses of correlation, comparison, and survival in three modes: Individual, Pan-cancer and Batch screen. Additionally, the tool includes download interfaces that enable users to access diverse data and outcomes, several features also facilitate the joint analysis of drug sensitivity and multi-omics of cancer cell lines. UCSCXenaShiny v2 is an open-source R package and a web application, freely accessible at https://github.com/openbiox/UCSCXenaShiny .

Microbial diversity in camel milk from Xinjiang, China as revealed by metataxonomic analysis.

The quality of raw camel milk is affected by its bacterial composition and diversity. However, few studies have investigated the bacterial composition and diversity of raw camel milk. In this study, we obtained 20 samples of camel milk during spring and summer in Urumqi and Hami, Xinjiang, China. Single-molecule real-time sequencing technology was used to analyze the bacterial community composition. The results revealed that there were significant seasonal differences in the bacterial composition and diversity of camel milk. Overall, Epilithonimonas was the most abundant bacterial genus in our samples. Through the annotated genes inferred by PICRUSt2 were mapped against KEGG database. Non-parametric analysis of the bacterial community prediction function revealed a strong bacterial interdependence with metabolic pathways (81.83%). There were clear regional and seasonal differences in level 3 metabolic pathways such as fat, vitamins, and amino acids in camel milk. In addition, we identified lactic acid bacteria in camel milk with antibacterial and anti-tumor activities. Our findings revealed that camel milk from Xinjiang had serious risk of contamination by psychrophilic and pathogenic bacteria. Our research established a crucial theoretical foundation for ensuring the quality and safety of camel milk, thereby contributing significantly to the robust growth of China's camel milk industry.

Cadmium-tolerant Bacillus cereus 2-7 alleviates the phytotoxicity of cadmium exposure in banana plantlets.

Bananas are the world's important fruit and staple crop in the developing countries. Cadmium (Cd) contamination in soils results in the decrease of crop yield and food safety. Bioremediation is an environmental-friendly and effective measure using Cd-tolerant plant growth promoting rhizobacteria (PGPR). In our study, a Cd-resistant PGPR Bacillus cereus 2-7 was isolated and identified from a discarded gold mine. It could produce multiple plant growth promoting biomolecules such as siderophores, indole-3-acetic acid (IAA), 1-aminocyclopropane-1-carboxylate (ACC)-deaminase and phosphatase. The extracellular accumulation was a main manner of Cd removal. Surplus Cd induced the expression of Cd resistance/transport genes of B. cereus 2-7 to maintain the intracellular Cd homeostasis. The pot experiment showed that Cd contents decreased by 50.31 % in soil, 45.43 % in roots, 56.42 % in stems and 79.69 % in leaves after the strain 2-7 inoculation for 40 d. Bacterial inoculation alleviated the Cd-induced oxidative stress to banana plantlets, supporting by the increase of chlorophyll contents, plant height and total protein contents. The Cd remediation mechanism revealed that B. cereus 2-7 could remodel the rhizosphere bacterial community structure and improve soil enzyme activities to enhance the immobilization of Cd. Our study provides a Cd-bioremediation strategy using Cd-resistant PGPR in tropical and subtropical area.

Enantioselective Synthesis and Biological Evaluation of Pyrrolidines Bearing Quaternary Stereogenic Centers.

Molecular complexity plays an increasingly important role in the modern pharmaceutical industry. Setting up multiple stereogenic centers in privileged substructures may give rise to improved or even unprecedented bioactivities; however, this area remains largely unexplored due to the tremendous synthetic challenges. Herein, we report a series of multisubstituted pyrrolidines with four continuous stereogenic centers, including up to two aza-QSCs (quaternary stereogenic centers). Systematic evaluations, including phenotypic screening, molecular docking, molecular dynamics, bioinformatics, and bioactivity analysis, have been performed to screen entities with pharmacological properties of interest. Among them, compound 4m with two QSCs was identified to be a potent antiproliferation agent through disturbing mitosis exit, and the presence of QSCs was found to be crucial for anticancer efficacy. This work illustrates that the introduction of QSCs in privileged scaffolds not only helps to expand the unpatented chemical space but also provides new opportunities for the discovery of novel therapeutic agents.

SNHG1/miR-186/FUT8 regulates cell migration and invasion in oral squamous cell carcinoma.

Recently, lncRNAs are associated with the progression and development of various cancers. We aimed to explore the effects of lncRNA SNHG1 on the proliferation, apoptosis, migration, and invasion of oral squamous cell carcinoma (OSCC) cells. Quantitative real-time PCR (RT-qPCR) was used for measurement of SNHG1 in OSCC cells. Cell proliferation, apoptosis, migration, and invasion were detected by CCK-8 assay, flow cytometry, Cell Death Detection ELISA PLUS kit, and transwell assays. Dual-luciferase reporter assay and RNA-binding protein immunoprecipitation (RIP) assay were used to clarify the relationship between SNHG1 and miR-186. SNHG1 was overexpressed in OSCC cells. SNHG1 silencing prevented cell proliferation and increased the incidence of apoptosis, DNA fragments, cleaved-caspase 3, and Bax protein levels. Cell migration and invasion were reduced after SNHG1 deletion, and MMP2 and MMP9 protein levels were decreased. SNHG1 overexpression promoted cell survival, migration, and invasion, reduced DNA fragments formation. Mechanistically, we demonstrated that SNHG1 could directly bind to miR-186 and positively regulated α1, 6-fucosyltransferase (FUT8) level. Functional investigation showed that miR-186 depletion reversed the roles of SNHG1 silencing in cell proliferation, apoptosis, and migration. Taken together, our findings illuminated that SNHG1 regulated cell proliferation, migration, and invasion by sponging miR-186 to depress FUT8 expression.

A combined predictive model based on radiomics features and clinical factors for disease progression in early-stage non-small cell lung cancer treated with stereotactic ablative radiotherapy.

Purpose: To accurately assess disease progression after Stereotactic Ablative Radiotherapy (SABR) of early-stage Non-Small Cell Lung Cancer (NSCLC), a combined predictive model based on pre-treatment CT radiomics features and clinical factors was established. Methods: This study retrospectively analyzed the data of 96 patients with early-stage NSCLC treated with SABR. Clinical factors included general information (e.g. gender, age, KPS, Charlson score, lung function, smoking status), pre-treatment lesion status (e.g. diameter, location, pathological type, T stage), radiation parameters (biological effective dose, BED), the type of peritumoral radiation-induced lung injury (RILI). Independent risk factors were screened by logistic regression analysis. Radiomics features were extracted from pre-treatment CT. The minimum Redundancy Maximum Relevance (mRMR) and the Least Absolute Shrinkage and Selection Operator (LASSO) were adopted for the dimensionality reduction and feature selection. According to the weight coefficient of the features, the Radscore was calculated, and the radiomics model was constructed. Multiple logistic regression analysis was applied to establish the combined model based on radiomics features and clinical factors. Receiver Operating Characteristic (ROC) curve, DeLong test, Hosmer-Lemeshow test, and Decision Curve Analysis (DCA) were used to evaluate the model's diagnostic efficiency and clinical practicability. Results: With the median follow-up of 59.1 months, 29 patients developed progression and 67 remained good controlled within two years. Among the clinical factors, the type of peritumoral RILI was the only independent risk factor for progression (P< 0.05). Eleven features were selected from 1781 features to construct a radiomics model. For predicting disease progression after SABR, the Area Under the Curve (AUC) of training and validation cohorts in the radiomics model was 0.88 (95%CI 0.80-0.96) and 0.80 (95%CI 0.62-0.98), and AUC of training and validation cohorts in the combined model were 0.88 (95%CI 0.81-0.96) and 0.81 (95%CI 0.62-0.99). Both the radiomics and the combined models have good prediction efficiency in the training and validation cohorts. Still, DeLong test shows that there is no difference between them. Conclusions: Compared with the clinical model, the radiomics model and the combined model can better predict the disease progression of early-stage NSCLC after SABR, which might contribute to individualized follow-up plans and treatment strategies.

MicroRNA-34a inhibits tumor invasion and metastasis in osteosarcoma partly by effecting C-IAP2 and Bcl-2.

Osteosarcoma is a common primary malignant bone tumor that occurs mainly in children and adolescents. Recent evidence has demonstrated that miR-34a is involved in the invasion and metastasis of osteosarcoma. This study aims to explore the effect of biological behavior of miR-34a on osteosarcoma. First, we collect osteosarcoma and adjacent specimens, and the relative expression of miR-34a and C-IAP2 messenger RNA was quantitated by real-time polymerase chain reaction. Furthermore, miR-34a stimulant is synthesized and transfected onto osteosarcoma MG-63 cells. The effect of overexpression of miR-34a on osteosarcoma was detected by colony-forming assay, Annexin V-fluorescein isothiocyanate Apoptosis Detection Kit I, Transwell assay, and animal experiment in vivo. Finally, the relative levels of C-IAP2 and Bcl-2 protein were checked by western blot, and the activity of caspase-3 and caspase-9 was tested by spectrophotometry assay. In conclusion, miR-34a was downregulated in osteosarcoma cells. And the expression of C-IAP2 and Bcl-2 protein was drastically inhibited, and the activities of caspase-3 and caspase-9 were significantly increased after transfecting miR-34a onto osteosarcoma MG-63 cells. And the overexpression of miR-34a can inhibit cell invasion and metastasis, promote cell apoptosis, and arrest cells in G0/G1 period. And the animal experiment in vivo demonstrated that the overexpression of miR-34a could significantly inhibit the growth of osteosarcoma in animal skin. Taken together, we indicated that miR-34a can inhibit tumor invasion and metastasis in osteosarcoma, and its mechanism may be partly related to downregulating the expression of C-IAP2 and Bcl-2 protein directly or indirectly.

[Co-culture with umbilical cord mesenchymal stem cells promotes the synthesis and mechnism of milk protein in bovine mammary epithelial cells].

Objective: To explore the possible mechanism of umbilical cord mesenchymal stem cels( UCMSCs) regulating milk protein synthesis in bovine mammary gland epithelial cells( BMECs). Methods: UCMSCs and BMECs were co-cultured by double-chamber TranswellTM,and other BMECs were cultured alone as a control group. Insulin like growth factor 1 receptor( IGF-1R) inhibitor AG1024 was used to treat cells. IGF-1,ß casein( CSN2) and κ casein( CSN3) content in the supernatants were determined by ELISA; the relative expression abundance of Janus kinase and signal transducer and activator of transcription factor( JAK / STAT) signaling pathway-related genes were detected by quantitative real-time PCR( qRT-PCR); and after the cells were treated with JAK2 signal blocker AG490,qRT-PCR was performed to test the relative expression abundance of CSN2 and CSN3 mRNAs. Results: CSN2, CSN3 synthetic quantity, and the relative expression abundance of CSN2,CSN3,JAK2,STAT5,E74-like ETS transcription factor 5( ELF5) mRNAs of the co-culture group were significantly higher than those of the control group. After treated with AG1024,the co-culture group showed remarkably decreased CSN2,CSN3 synthesis in BMECs as wel as the decreased relative expression abundance of CSN2,CSN3,JAK2,STAT5,ELF5 mRNAs. After blocked with AG490,the relative expression abundance of CSN2 and CSN3 mRNAs were reduced significantly in the co-culture group. In addition,the expressions of CSN2 and CSN3 mRNAs were inhibited significantly when both AG1024 and AG490 were supplemented. Conclusion: UCMSCs can mediate JAK2 / STAT5 signaling pathwayvia IGF-1,and increase the expressions of milk protein synthesis key genes in BMECs,thus promoteing the synthesis of milk protein.