Optimal configuration of a wildlife corridor system

Establishing wildlife corridors to link detached habitat patches is a widely advocated conservation strategy to reduce the adverse impacts of habitat fragmentation. Given the scarcity of conservation resources, designing an efficient corridor system calls for an optimization approach. The optimal configuration of a wildlife corridor system involving multiple habitat patches poses significant challenges, both methodologically and computationally. This study proposes a two-stage procedure for that purpose. In the first stage, we determine a best-quality corridor between each pair of habitat patches using the method described in Wang et al. (2022). In the second stage, we select a subset of those corridors to assemble a least-cost corridor system using a mixed integer linear programming model presented in this paper. We use an illustrative example to demonstrate the workings of the two-stage method, and then apply it to a real dataset for an area in Cumberland County, Nova Scotia, Canada, involving 1039 irregular land parcels. Results show that an efficient corridor system where each habitat patch is connected to some neighboring habitat patches through a specified minimum number of corridors can be identified conveniently in terms of both data processing and computational effort

Guiding Drug Repositioning for Cancers Based on Drug Similarity Networks

Drug repositioning aims to discover novel clinical benefits of existing drugs, is an effective way to develop drugs for complex diseases such as cancer and may facilitate the process of traditional drug development. Meanwhile, network-based computational biology approaches, which allow the integration of information from different aspects to understand the relationships between biomolecules, has been successfully applied to drug repurposing. In this work, we developed a new strategy for network-based drug repositioning against cancer. Combining the mechanism of action and clinical efficacy of the drugs, a cancer-related drug similarity network was constructed, and the correlation score of each drug with a specific cancer was quantified. The top 5% of scoring drugs were reviewed for stability and druggable potential to identify potential repositionable drugs. Of the 11 potentially repurposable drugs for non-small cell lung cancer (NSCLC), 10 were confirmed by clinical trial articles and databases. The targets of these drugs were significantly enriched in cancer-related pathways and significantly associated with the prognosis of NSCLC. In light of the successful application of our approach to colorectal cancer as well, it provides an effective clue and valuable perspective for drug repurposing in cancer

Integrating Expression Data-Based Deep Neural Network Models with Biological Networks to Identify Regulatory Modules for Lung Adenocarcinoma

Lung adenocarcinoma is the most common type of primary lung cancer, but the regulatory mechanisms during carcinogenesis remain unclear. The identification of regulatory modules for lung adenocarcinoma has become one of the hotspots of bioinformatics. In this paper, multiple deep neural network (DNN) models were constructed using the expression data to identify regulatory modules for lung adenocarcinoma in biological networks. First, the mRNAs, lncRNAs and miRNAs with significant differences in the expression levels between tumor and non-tumor tissues were obtained. MRNA DNN models were established and optimized to mine candidate mRNAs that significantly contributed to the DNN models and were in the center of an interaction network. Another DNN model was then constructed and potential ceRNAs were screened out based on the contribution of each RNA to the model. Finally, three modules comprised of miRNAs and their regulated mRNAs and lncRNAs with the same regulation direction were identified as regulatory modules that regulated the initiation of lung adenocarcinoma through ceRNAs relationships. They were validated by literature and functional enrichment analysis. The effectiveness of these regulatory modules was evaluated in an independent lung adenocarcinoma dataset. Regulatory modules for lung adenocarcinoma identified in this study provided a reference for regulatory mechanisms during carcinogenesis

Linc01588 deletion inhibits the malignant biological characteristics of hydroquinone-induced leukemic cells via miR-9-5p/SIRT1

Leukemia caused by environmental chemical pollutants has attracted great attention, the malignant leukemic transformation model of TK6 cells induced by hydroquinone (HQ) has been previously found in our team. However, the type of leukemia corresponding to this malignant transformed cell line model needs further study and interpretation. Furthermore, the molecular mechanism of malignant proliferation of leukemic cells induced by HQ remains unclear. This study is the first to reveal the expression of aberrant genes in leukemic cells of HQ-induced malignant transformation, which may correspond to chronic lymphocytic leukemia (CLL). The expression of Linc01588, a long non-coding RNA (lncRNA), was significantly up-regulated in CLL patients and leukemic cell line model which previously described. After gain-of-function assays and loss-of-function assays, feeble cell viability, severe apoptotic phenotype and the increased secretion of TNF-α were easily observed in malignant leukemic TK6 cells with Linc01588 deletion after HQ intervention. The tumors derived from malignant TK6 cells with Linc01588 deletion inoculated subcutaneously in nude mice were smaller than controls. In CLL and its cell line model, the expression of Linc01588 and miR-9–5p, miR-9–5p and SIRT1 were negative correlation respectively in CLL and cell line model, while the expression of Linc01588 and SIRT1 were positive correlation. The dual-luciferase reporter assay showed that Linc01588 & miR-9–5p, miR-9–5p & SIRT1 could bind directly, respectively. Furthermore, knockdown of miR-9–5p successfully rescued the severe apoptotic phenotype and the increased secretion of TNF-α caused by the Linc01588 deletion, the deletion of Linc01588 in human CLL cell line MEC-2 could also inhibit malignant biological characteristics, and the phenotype caused by the deletion of Linc01588 could also be rescued after overexpression of SIRT1. Moreover, the regulation of SIRT1 expression in HQ19 cells by Linc01588 and miR-9–5 P may be related to the Akt/NF-κB pathway. In brief, Linc01588 deletion inhibits the malignant biological characteristics of HQ-induced leukemic cells via miR-9–5p/SIRT1, and it is a novel and hopeful clue for the clinical targeted therapy of CLL

Isoliquiritigenin induces HMOX1 and GPX4-mediated ferroptosis in gallbladder cancer cells

Abstract. Background:. Gallbladder cancer (GBC) is the most common malignant tumor of biliary tract. Isoliquiritigenin (ISL) is a natural compound with chalcone structure extracted from the roots of licorice and other plants. Relevant studies have shown that ISL has a strong anti-tumor ability in various types of tumors. However, the research of ISL against GBC has not been reported, which needs to be further investigated. Methods:. The effects of ISL against GBC cells in vitro and in vivo were characterized by cytotoxicity test, RNA-sequencing, quantitative real-time polymerase chain reaction, reactive oxygen species (ROS) detection, lipid peroxidation detection, ferrous ion detection, glutathione disulphide/glutathione (GSSG/GSH) detection, lentivirus transfection, nude mice tumorigenesis experiment and immunohistochemistry. Results:. ISL significantly inhibited the proliferation of GBC cells in vitro. The results of transcriptome sequencing and bioinformatics analysis showed that ferroptosis was the main pathway of ISL inhibiting the proliferation of GBC, and HMOX1 and GPX4 were the key molecules of ISL-induced ferroptosis. Knockdown of HMOX1 or overexpression of GPX4 can reduce the sensitivity of GBC cells to ISL-induced ferroptosis and significantly restore the viability of GBC cells. Moreover, ISL significantly reversed the iron content, ROS level, lipid peroxidation level and GSSG/GSH ratio of GBC cells. Finally, ISL significantly inhibited the growth of GBC in vivo and regulated the ferroptosis of GBC by mediating HMOX1 and GPX4. Conclusion:. ISL induced ferroptosis in GBC mainly by activating p62-Keap1-Nrf2-HMOX1 signaling pathway and down-regulating GPX4 in vitro and in vivo. This evidence may provide a new direction for the treatment of GBC

<b>Prediction of the recurrence of differentiated thyroid carcinoma by post-operative neutrophil and platelet count</b>

Objective: The present study aimed to combine pre- and post-operative peripheral blood laboratory indicators with clinicopathological characteristics to predict differentiated thyroid carcinoma (DTC) recurrence. Study Design: Retrospective case-control analysis.Methods: From June 2013 to December 2020, 488 patients with DTC received treatment at The Second Affiliated Hospital of Guangxi University of Science and Technology. Pre- and post-operative inflammatory marker levels and clinicopathological features were obtained from the medical record system. Kaplan–Meier survival analysis and proportional hazards model were used to assess the DTC recurrence risk. The nomogram was developed to estimate the predictive power of the indicators by the C-index, area under the curve (AUC) and calibration curves. Results: 36 (7.38%) of 488 DTC patients suffered recurrence. Lymph node metastases (LNMs) (hazard ratio [HR]=12.07, 95%CI: 1.82–79.97, P=0.010), tumor diameter ≥2 cm (HR=3.78, 95%CI:1.55-9.25, P=0.004), post-operative neutrophil count (post-NEU)>4.78 109/L (HR=0.29, 95%CI:0.11-0.73, P=0.008), and post-operative platelets count (post-PLT)>316 109/L(HR=2.82, 95%CI:1.37-5.81, P=0.005) were independent risk factors for DTC recurrence. The median AUC values for predicting the recurrence of DTC at 2 years and 3 years were 0.86 (range: 0.75-0.97) and 0.84 (0.72-0.95), respectively. Patients with higher risk in nomogram had lower Recurrence-free survival (RFS) rate at both 2 years and 3 years (all P<0.001). Conclusion: In the present study, DTC patients with LNMs, tumor diameter ≥2 cm, higher post-NEU level, and higher post-PLT level exhibited an increased risk of DTC recurrence. The prediction model incorporating these characteristics robust thereby offering valuable insights into the prognostication of DTC patients in practical healthcare applications.</p