Role of mitochondria in early molecular diagnosis and prognosis of cancer

Background:Earlier clinical detection of cancer may improve survival as well as offer opportunities for less invasive treatment options. This thesis explores whether the mitochondria and its related genes in the nuclear genome can be used as novel methods for the diagnosis and prognosis of cancers.Aims and Methods:Paper I: To investigate if mitochondrial dysfunction (characterized by mtDNA copy number variations) is associated with prevalent, incident cancer and cancer mortality – droplet digital PCR (ddPCR).Paper II: To investigate the potential causal relationship between mitochondrial dysfunction (characterized by genetic predispositions in all mitochondrial-related genes) and common cancer risks – Mendelian randomization, colocalization.Paper III: To investigate mitochondrial mutations as potential biomarkers for the early diagnosis of breast cancer – whole mitochondrial genome sequencing, bioinformatics, ddPCR.Paper IV: To investigate the mitochondrial-related gene expression signature as a prognostic model to predict the clinical outcome for breast cancer patients – machine learning.Results and conclusions:Paper I: We found that mtDNA-CN was significantly associated with prevalent and incident cancer as well as cancer mortality. However, these associations were cancer-type specific and need further investigation.Paper II: We identified potential causal relationships between mitochondrial-related genes and breast, prostate and lung cancer. Furthermore, this study identified candidate genes that can be the targets of potential pharmacological agents for cancer prevention.Paper III: We comprehensively characterized the mtDNA mutation landscape of breast cancer biopsies and matched baseline whole blood samples. Notably, we have identified and validated mt.16093T>C mutation, which was associated with a 67% increased risk of developing breast cancer, and could potentially be used as early breast cancer diagnostic biomarkers.Paper IV: We built a novel 14 genes mitochondrial signature model that could be an independent prognostic predictor and together with clinical variables as an improved model for predicting overall earlystage of breast cancer survival

Global Dynamics and Applications of an Epidemiological Model for Hepatitis C Virus Transmission in China

An epidemiological model is proposed and studied to understand the transmission dynamics and prevalence of HCV infection in China. Theoretical analysis indicates that the basic reproduction number R0 provides a threshold value determining whether the disease dies out or not. Two Lyapunov functions are constructed to prove the global asymptotic stability of the disease-free and the endemic equilibria, respectively. Based on data reported by the National Health and Family Planning Commission of China, the basic reproduction number is estimated as approximately R0=1.9897, which is much less than that for the model when a treatment strategy is not considered. An ever-increasing HCV infection is predicted in the near future. Numerical simulations, performed to investigate the potential effect of antiviral treatment, show that increasing the treatment cure rate and enlarging the treatment rate for patients at the chronic stage remain effective in reducing the number of new infections and the equilibrium prevalence. The finding suggests that treatment measures are significantly beneficial for disease control in terms of reducing new infections and, in particular, more attention should be paid to treatment for patients at the chronic stage

Research on One Novel Logging Interpretation Method of CBM Reservoir

Coalbed methane (CBM) is a kind of natural gas which is stored in the micropores and fractures of the “coal seam” and has not been transported out of the source rock. Conventional logging technology plays an important role in coalbed methane exploration and development. By analyzing the response characteristics of conventional logging of coalbed methane, coal bearing strata are accurately determined. Two methods of statistical model and volume model are established to analyze and calculate industrial components. Based on the study of adsorption isotherm and correlation between logging parameters and coal core gas content, the calculation method of coal seam gas content is determined In practices, the calculation accuracy of industrial components and gas content of coal seam has been significantly improved. Abstract: coalbed methane (CBM) is a kind of natural gas which is stored in the micropores and fractures of “coal seam” and has not been transported out of the source rock. Conventional logging technology plays an important role in coalbed methane exploration and development. By analyzing the response characteristics of conventional logging of coalbed methane, coal bearing strata are accurately determined. Two methods of statistical model and volume model are established to analyze and calculate industrial components. Based on the study of adsorption isotherm and correlation between logging parameters and coal core gas content, the calculation method of coal seam gas content is determined In practice, the calculation accuracy of industrial components and gas content of coal seam has been significantly improved

Distinct composition and amplification dynamics of transposable elements in sacred lotus (Nelumbo nucifera Gaertn.)

Sacred lotus (Nelumbo nucifera Gaertn.) is a basal eudicot plant with a unique lifestyle, physiological features, and evolutionary characteristics. Here we report the unique profile of transposable elements (TEs) in the genome, using a manually curated repeat library. TEs account for 59% of the genome, and hAT (Ac/Ds) elements alone represent 8%, more than in any other known plant genome. About 18% of the lotus genome is comprised of Copia LTR retrotransposons, and over 25% of them are associated with non-canonical termini (non-TGCA). Such high abundance of non-canonical LTR retrotransposons has not been reported for any other organism. TEs are very abundant in genic regions, with retrotransposons enriched in introns and DNA transposons primarily in flanking regions of genes. The recent insertion of TEs in introns has led to significant intron size expansion, with a total of 200 Mb in the 28 455 genes. This is accompanied by declining TE activity in intergenic regions, suggesting distinct control efficacy of TE amplification in different genomic compartments. Despite the prevalence of TEs in genic regions, some genes are associated with fewer TEs, such as those involved in fruit ripening and stress responses. Other genes are enriched with TEs, and genes in epigenetic pathways are the most associated with TEs in introns, indicating a dynamic interaction between TEs and the host surveillance machinery. The dramatic differential abundance of TEs with genes involved in different biological processes as well as the variation of target preference of different TEs suggests the composition and activity of TEs influence the path of evolution

Glycogen synthase kinase-3β inhibition induces nuclear factor-κB-mediated apoptosis in pediatric acute lymphocyte leukemia cells

<p>Abstract</p> <p>Background</p> <p>Molecular therapies that target genetic abnormalities in leukemic cells and their affected signaling pathways have been emerging in pediatric acute lymphoblastic leukemia (ALL). Glycogen synthase kinase-3β (GSK-3β) has recently been found to positively regulate the activity of nuclear factor-κB (NF-κB). Here, we investigated the relationship between GSK-3β inhibition and NF-κB in apoptosis of pediatric primary leukemia cells obtained from 39 newly diagnosed ALL children in China.</p> <p>Methods</p> <p>Bone marrow mononuclear cells (BMMC) were isolated by density gradient centrifugation from the heparinized aspirates of children with ALL. We used immunofluorescence staining to detect nuclear GSK-3β in these cells. After treatment with chemically distinct GSK-3β inhibitors in vitro, NF-κB transcriptional activity was identified by means of western blotting and electrophoretic mobility shift assay (EMSA). NF-κB-mediated apoptosis was detected by Annexin V-PE/7-AAD double-staining flow cytometry. The expression level of the <it>survivin </it>gene was detected by reverse-transcriptase polymerase chain reaction (RT-PCR).</p> <p>Results</p> <p>GSK-3β significantly accumulates in the nuclei of ALL cells than in the nuclei of control cells. Cell death induced by GSK-3β inhibition in ALL cells was mediated by a downregulation of NF-κB p65 transcriptional activity. GSK-3β inhibition significantly decreased the expression of the NF-κB target gene <it>survivin</it>.</p> <p>Conclusions</p> <p>These results indicate that inhibition of GSK-3β downregulates the NF-κB activation pathway, leading to suppression of the expression of an NF-κB-regulated gene and promotion of apoptosis in ALL cells in vitro. Furthermore, our findings suggest that GSK-3β or NF-κB is a potential therapeutic target in the treatment of pediatric ALL.</p

Efficient Geometric Correction Workflow for Airborne Hyperspectral Images through DEM-Driven Correction Techniques

Geometric correction, a pivotal step in the preprocessing of airborne remote sensing imagery, is critical for ensuring the accuracy of subsequent quantitative analyses. Achieving precise and efficient geometric correction for airborne hyperspectral data remains a significant challenge in the field. This study presents a new method for system-level and fine-scale geometric correction of uncontrolled airborne images utilizing DEM data, which integrates forward and inverse transformation algorithms. Furthermore, an optimized workflow is proposed to facilitate the processing of large-scale hyperspectral datasets. The effectiveness of the proposed method is demonstrated through an application analysis using airborne HyMap imagery, with experimental outcomes indicating high application accuracy and enhanced processing efficiency

Conjunctival Flap Covering Combined with Antiviral and Steroid Therapy for Severe Herpes Simplex Virus Necrotizing Stromal Keratitis

Herpes simplex virus (HSV) necrotizing stromal keratitis is a common type of herpetic stromal keratitis (HSK). Antiviral medication alone cannot control the disease, and corticosteroid eye drops may aggravate the ulcer and result in corneal perforation. Amniotic membrane transplantation effectively treats superficial corneal ulcer resulting from necrotizing stromal HSK. However, the efficacy of this approach seems to be limited for more serious cases. This study presented the clinical treatment of severe HSV necrotizing stromal keratitis (ulcer depth greater than half of the corneal stroma) by conjunctival flap covering surgery in 25 patients (25 eyes) combined with antivirus and corticosteroid treatment at Shandong Eye Hospital from January 2007 to December 2013. Clinical results showed that the mean best spectacle-corrected visual acuity improved from preoperative 20/333 to postoperative 20/40 (P<0.05). All patients recovered ocular surface stabilization. There was recurrence in two eyes, which was cured with antiviral medication. Conjunctival flap covering combined with antivirus and corticosteroid treatment is effective in treating severe HSV necrotizing stromal keratitis

Nurse-led cognitive screening model for older adults in primary care

Author version made available in accordance with publisher copyright. Under 12 month embargo from date of publication [26 September 2014]. This is the accepted version of the following article: [Yang, Y., Xiao, L. D., Deng, L., Wang, Y., Li, M. and Ullah, S. (2014), Nurse-led cognitive screening model for older adults in primary care. Geriatrics & Gerontology International.], which has been published in final form at [doi: 10.1111/ggi.12339]. In addition, authors may also transmit, print and share copies with colleagues, provided that there is no systematic distribution of the submitted version, e.g. posting on a listserve, network or automated delivery.Aim The present study aimed to establish a nurse-led cognitive screening model for community-dwelling older adults with subjective memory complaints from seven communities in Chongqing, China, and report the findings of this model. Methods Screenings took place from July 2012 to June 2013. Cognitive screening was incorporated into the annual health assessment for older adults with subjective memory complaints in a primary care setting. Two community nurses were trained to implement the screening using the Mini-Mental State Examination and Montreal Cognitive Assessment. Results Of 733 older adults, 495 (67.5%) reported having subjective memory complaints. Of the 249 individuals who participated in the cognitive screening, 102 (41%) had mild cognitive impairment, whereas 32 (12.9%) had cognitive impairment. A total of 80 participants (78.4%) with mild cognitive impairment agreed to participate in a memory support program. Participants with cognitive impairment were referred to specialists for further examination and diagnosis; only one reported that he had seen a specialist and had been diagnosed with dementia. Conclusions Incorporating cognitive screening into the annual health assessment for older adults with subjective memory complaints was feasible, though referral rates from primary care providers remained unchanged. The present study highlights the urgent need for simple screenings as well as community-based support services in primary care for older adults with cognitive or mild cognitive impairments