Mitochondrial Fission in Nickel Nanoparticle-Induced Reproductive Toxicity: An In Vitro GC-1 Cell Study.

Reproductive disorders and declining fertility rates are significant public health concerns affecting birth rates and future populations. Male infertility, often due to spermatogenesis defects, may be linked to environmental pollutants like nickel nanoparticles (Ni NPs). Ni NPs are extensively utilized across different industries. Nevertheless, their potential adverse effects cannot be overlooked. Previous studies have linked the reproductive toxicity induced by Ni NPs with disturbances in mitochondrial function. Mitochondrial division/fusion dynamics are crucial to their proper function, yet little is known about how Ni NPs perturb these dynamics and whether such perturbation contributes to the impairment of the male reproductive system. Herein, we demonstrated that the exposure of Ni NPs to the mouse-derived spermatogonia cell line (GC-1 cells) triggered DRP1-mediated mitochondrial division and the enhanced impairment of mitochondria, consequently promoting mitochondria-dependent cell apoptosis. Notably, both the mitochondrial division inhibitor (Mdivi-1) and lentiviral-transfected cells with low expression of Dnm1l-DK in these cells could mitigate the toxic effects induced by Ni NPs, pointing to the potential role of mitochondrial dynamics in Ni NP-induced reproductive toxicity. Collectively, our work contributes to the understanding of the mechanisms by which Ni NPs can impact male reproductive function and identifies mitochondrial division as a potential target for intervention.

Synthesis of tunable thickness-to-diameter ratio microcapsules via a diffusion-controlled process for temperature-responsive release.

Designing microcapsules with a complicated functionalized shell to respond to an external stimulus has attracted much attention for triggered release; however, simplifying the synthesis process remains a significant challenge. Herein, we initially propose a novel, simple synthesis strategy that utilizes a mixed solvent as the organic phase to control the diffusion of common monomers during interfacial polymerization, resulting in the successful preparation of microcapsules with tunable thickness-to-diameter ratios (T/D). The morphology of microcapsules is confirmed by scanning electron microscopy. We also observe that the T/D of the designed microcapsules progressively increases as the diffusion of monomers occurs, and the glass transition temperature of microcapsules is controlled. Furthermore, microcapsule-based crosslinking agents are applied to investigate the crosslinking reaction of poly(vinyl chloride). Rotational rheometer results indicate that the microcapsules exhibit an excellent external stimulus response, precisely triggering release at the predetermined temperature. This simple approach for the preparation of microcapsules with tunable physical properties has great potential for triggered release in diverse applications.

Intratumoral Delivery of Interleukin 9 via Oncolytic Vaccinia Virus Elicits Potent Antitumor Effects in Tumor Models.

The success of cancer immunotherapy is largely associated with immunologically hot tumors. Approaches that promote the infiltration of immune cells into tumor beds are urgently needed to transform cold tumors into hot tumors. Oncolytic viruses can transform the tumor microenvironment (TME), resulting in immunologically hot tumors. Cytokines are good candidates for arming oncolytic viruses to enhance their function in this transformation. Here, we used the oncolytic vaccinia virus (oVV) to deliver interleukin-9 (IL-9) into the tumor bed and explored its antitumor effects in colon and lung tumor models. Our data show that IL-9 prolongs viral persistence, which is probably mediated by the up-regulation of IL-10. The vvDD-IL-9 treatment elevated the expression of Th1 chemokines and antitumor factors such as IFN-γ, granzyme B, and perforin. IL-9 expression increased the percentages of CD4+ and CD8+ T cells in the TME and decreased the percentage of oVV-induced immune suppressive myeloid-derived suppressor cells (MDSC), leading to potent antitumor effects compared with parental virus treatment. The vvDD-IL-9 treatment also increased the percentage of regulatory T cells (Tregs) in the TME and elevated the expression of immune checkpoint molecules such as PD-1, PD-L1, and CTLA-4, but not GITR. The combination therapy of vvDD-IL-9 and the anti-CTLA-4 antibody, but not the anti-GITR antibody, induced systemic tumor-specific antitumor immunity and significantly extended the overall survival of mice, indicating a potential translation of the IL-9-expressing oncolytic virus into a clinical trial to enhance the antitumor effects elicited by an immune checkpoint blockade for cancer immunotherapy.

A Novel One-Step Reactive Extrusion Process for High-Performance Rigid Crosslinked PVC Composite Fabrication Using Triazine Crosslinking Agent@Melamine-Formaldehyde Microcapsules.

In this work, we propose, for the first time, a simple, fast, and efficient strategy to fabricate high-performance rigid crosslinked PVC composites by continuous extrusion. This strategy improves the poor processing fluidity of composites and solves the impossibility of conducting extrusion in one step via using microcapsule-type crosslinking agents prepared by in situ polymerization to co-extrude with PVC blends. The results demonstrate that the PVC/microcapsule composites were successfully prepared. Within the studied parameters, the properties of crosslinked PVC gradually increased with the addition of microcapsules, and its Vicat softening temperature increased from 79.3 °C to 86.2 °C compared with pure PVC. This study shows the possibility for the industrial scale-up of the extrusion process for rigid crosslinked PVC.

Nickel nanoparticles exert cytotoxic effects on trophoblast HTR-8/SVneo cells possibly via Nrf2/MAPK/caspase 3 pathway.

Nickel nanoparticles are widely used in the industry and may affect the reproductive system. The potential molecular mechanism of exposing the first-trimester trophoblast cell line (HTR-8/SVneo) to nickel nanoparticles remains unclear. Hence, the aim of this study was to investigate the in vitro cytotoxicity of Ni NPs on HTR-8/SVneo cells. HTR-8/SVneo cells were subjected to various concentrations (0, 2.5, 5, 7.5, 10, and 12.5 µg/cm2) of Ni NPs. The toxicity of the Ni NPs was evaluated in HTR-8/SVneo cells by measuring cell viability. The underlying mechanism of nickel nanoparticles toxicity to HTR-8/SVneo cells was determined by measuring the content of intracellular reactive oxygen species, mitochondrial membrane potential, and the rate of cell apoptosis and cell cycle, by measuring adenosine triphosphate levels, intracellular lipid peroxidation malondialdehyde, total superoxide dismutase, and CuZn/Mn-SOD activities, and by determining proteins related to Nrf2, MAPK, and Cytochrome c. Our results showed that the nickel nanoparticles treatment reduced the viability of HTR-8/SVneo cells, while it increased their oxidative stress and lowered their mitochondrial respiratory capacity. Additionally, the nickel nanoparticles treatment induced cell S-phase arrest and apoptosis. These molecular events may be linked to the oxidative stress-Nrf2 pathway/MAPK/Caspase 3 cascade. Thus, nickel nanoparticles exert cytotoxic effects on HTR-8/SVneo cells, which could affect the function of the placenta in human.

ROS generation is involved in titanium dioxide nanoparticle-induced AP-1 activation through p38 MAPK and ERK pathways in JB6 cells.

Titanium dioxide (TiO2 ) is generally regarded as a nontoxic and nongenotoxic white mineral, which is mainly applied in the manufacture of paper, paint, plastic, sunscreen lotion and other products. Recently, TiO2 nanoparticles (TiO2 NPs) have been demonstrated to cause chronic inflammation and lung tumor formation in rats, which may be associated with the particle size of TiO2 . Considering the important role of activator protein-1 (AP-1) in regulating multiple genes involved in the cell proliferation and inflammation and the induction of neoplastic transformation, we aimed to evaluate the potency of TiO2 NPs (≤ 20 nm) on the activation of AP-1 signaling pathway and the generation of reactive oxygen species (ROS) in a mouse epidermal cell line, JB6 cells. MTT, electron spin resonance (ESR), AP-1 luciferase activity assay in vitro and in vivo, and Western blotting assay were used to clarify this problem. Our results indicated that TiO2 NPs dose-dependently caused the hydroxyl radical (·OH) generation and sequentially increased the AP-1 activity in JB6 cells. Using AP-1-luciferase reporter transgenic mice models, an obvious increased AP-1 activity was detected in dermal tissue after exposure to TiO2 NPs for 24 h. Interestingly, TiO2 NPs increased the AP-1 activity via stimulating the expression of mitogen-activated protein kinases (MAPKs) family members, including extracellular signal-regulated protein kinases (ERKs), p38 kinase, and C-Jun N-terminal kinases (JNKs). Of note, the AP-1 activation induced by TiO2 NPs could be blocked by specific inhibitors (SB203580, PD98059, and SP 600125, respectively) that inhibit ERKs and p38 kinase but not JNKs. These findings indicate that ROS generation is involved in TiO2 NPs-induced AP-1 activation mediated by MAPKs signal pathway.

Multi-omics study on biomarker and pathway discovery of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a common heterogeneous respiratory disease characterized by persistent and incompletely reversible airflow limitation. Due to the heterogeneity and phenotype complexity of COPD, traditional diagnostic methods can only provide limited information on predicted results and treatment, which are not sufficient for accurate diagnosis and evaluation. With the development of omics technologies in recent years, genomics, proteomics and metabolomics are widely used in the study of COPD, providing good tools for discovering biomarkers to diagnose and elucidate the complex mechanism of COPD. In this review, we summarize the biomarkers of COPD based on metabolomic, proteomic and transcriptomic studies that have been reported in recent years. Furthermore, protein-protein interactions and multi-omics integrated analyses were carried out to explore the important metabolites and proteins that are involved in significant pathways in the progression of COPD in order to explain the pathogenesis of COPD. Finally, the prospects and challenges in the study of COPD are proposed. It is expected that this review will provide some references for the development of diagnostic methods and elucidation of the pathogenesis of COPD.

Synthesis of Transition Metal Complexes and Their Effects on Combustion Properties of Semi-Rigid Polyvinyl Chloride.

Using introduction of MoO42- and Fe3+, Cu2+, or Zn2+ into amphiphilic polymers (DN) via an ion-exchange reaction, different transition metal complexes, as retardants and smoke suppressants, including (DN)Mo, Fe(DN)Mo, Cu(DN)Mo, and Zn(DN)Mo were synthesized. Combined with the results of X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR), it could be determined that ionic bonding of these ions with DN occurred. Subsequently, the influence of flame-retardant, smoke-suppression, and mechanical properties of (DN)Mo, Fe(DN)Mo, Cu(DN)Mo, and Zn(DN)Mo on polyvinyl Chloride (PVC) were tested. It was demonstrated that transition metal complexes of three metal elements, Fe(DN)Mo, Cu(DN)Mo, and Zn(DN)Mo, showed better flame retardancy, smoke suppression, and thermal stability as confirmed by microcalorimetry, limiting oxygen index (LOI), smoke density, and thermogravimetric analysis (TGA) tests, in which Cu(DN)Mo worked best due to the Lewis acid mechanism and reductive coupling mechanism. Scanning electron microscopy (SEM) showed that the addition of (DN)Mo, Fe(DN)Mo, Cu(DN)Mo, and Zn(DN)Mo promoted the formation of a dense carbon layer on the PVC surface during combustion, which could protect the interior PVC. The addition of these transition metal complexes hardly impaired the mechanical properties of PVC.

Joint Toxicity of a Multi-Heavy Metal Mixture and Chemoprevention in Sprague Dawley Rats.

To explore the joint toxicity and bio-accumulation of multi-heavy metals and potential chemoprevention strategies, Male Sprague Dawley (SD) rats (n = 30) were treated orally once a week for six months with 500mg/kg•bw of eight heavy metals which were commonly identified in aquatic products in the Ningbo area including chromium, manganese, nickel, copper, zinc, cadmium, mercury, and lead. At the same time, 200mg/kg•bw of epigallocatechin-3-gallate (EGCG), trisodium citrate dihydrate (TCD) or glutathione (GSH) were administered to evaluate their antagonistic effects against adverse effects of multi-heavy metal mixture. The Morris water maze test was used to evaluate spatial learning and memory in the treated rats. Then the rats were anesthetized by pentobarbital sodium (40 mg/kg•bw) to obtain blood samples for biochemical analysis and organs (heart, liver, spleen, lungs, kidneys, brain, testis) to be conducted for biopsy and organ coefficients. Inductively coupled plasma mass spectrometer (ICP-MS) was used to analyze the concentrations of heavy metals. Results indicated that six months of exposure to a multi-heavy metal mixture under this experimental dosage resulted in accumulation in organs and adverse effects on the blood, reproductive system, and liver function. EGCG, TCD or GSH all showed certain chemoprevention effects against the joint toxicity induced by the multi-heavy metal mixture and indicated alleviation and the potential mechanism that also included the promotion of excretion of metals to which animals were exposed.

Designing a general method for predicting the regulatory relationships between long noncoding RNAs and protein-coding genes based on multi-omics characteristics.

MOTIVATION: Long noncoding RNA (lncRNA) has been verified to interact with other biomolecules especially protein-coding genes (PCGs), thus playing essential regulatory roles in life activities and disease development. However, the inner mechanisms of most lncRNA-PCG relationships are still unclear. Our study investigated the characteristics of true lncRNA-PCG relationships and constructed a novel predictor with machine learning algorithms. RESULTS: We obtained the 307 true lncRNA-PCG pairs from database and found that there are significant differences in multiple characteristics between true and random lncRNA-PCG sets. Besides, 3-fold cross-validation and prediction results on independent test sets show the great AUC values of LR, SVM and RF, among which RF has the best performance with average AUC 0.818 for cross-validation, 0.823 and 0.853 for two independent test sets, respectively. In case study, some candidate lncRNA-PCG relationships in colorectal cancer were found and HOTAIR-COMP interaction was specially exemplified. The proportion of the reported pairs in the predicted positive results was significantly higher than that in negative results (P < 0.05). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Evaluation of the effectiveness of a pilot study of hospital-based hepatitis C epidemic surveillance.

The aim of this study was to evaluate the effectiveness of hospital-based hepatitis C epidemic surveillance initiated by China's CDC STD/AIDS (National Center for AIDS/STD Control and Prevention of Chinese Center for Disease Control and Prevention) Prevention and Control Center in 2017.A total of 104,666 anti-hepatitis C virus (HCV) and 633 HCV-RNA detection records in our hospital from 2014 to 2017 were used to analyze the anti-HCV and HCV-RNA detection rates and positive rates in patients before and after implementation of epidemic surveillance.We found that the estimated HCV positive rate was 0.395% in all patients, and this rate increased to 0.533% after the pilot research. The positive rates of anti-HCV were significantly enhanced, although certain differences were observed among different departments. Significant increase of positive rate of HCV-RNA was only found in the inpatients from nonsurgical departments. Eighty-one cases were diagnosed after this pilot research, exceeding the 70 total cases in the previous 3 years. Most cases were diagnosed by nonsurgical departments; the upward trend of the cases diagnosed by surgical departments cannot be ignored.Our study indicates expanding anti-HCV and HCV-RNA detection in the target populations in hospitals is a useful strategy for finding more occult HCV infection. In addition, our results provide useful pilot data of the seroepidemiology of Hepatitis C for the special populations in hospitals, which will provide valuable information for public health research.

Air pollution and placental mitochondrial DNA copy number: Mechanistic insights and epidemiological challenges.

During embryogenesis and embryo implantation, the copy number of mtDNA is elaborately regulated to meet the cellular demand for division, growth and differentiation. With large numbers of mitochondria for energy production, placental cells possess strong endocrine functionalities and capacities for efficient signaling communication. Recently, several environmental epidemiological studies have shown an association between mitochondrial DNA copy number, adverse birth outcomes and maternal exposure to air pollution, which has shed light on the possible effect of pollutants on placental molecular events. Because the mtDNA replication is thought to be a direct drive of mtDNA change, we tried to highlight the essential factors involved in the process of mtDNA replication. Then we traced the mtDNA change in the formation of placenta during embryogenesis, and evaluated the importance of mitochondrial genome maintenance during gestation. The possible mechanism from the epidemiological and experimental studies were reviewed and summarized, and recommendations were proposed for future studies to improve the precision of the estimated difference. The issue will be well-understood if the integrated profiles, such as familial genetic tendency, maternal genetic information, identification of mitochondrial DNA copy number in each placental cell type, and total personal exposure assessment, are considered in the future study.

Advances in biosensors for the detection of ochratoxin A: Bio-receptors, nanomaterials, and their applications.

Ochratoxin A (OTA) is a class of mycotoxin mainly produced by the genera Aspergillus and Penicillium. OTA can cause various forms of kidney, liver and brain diseases in both humans and animals although trace amount of OTA is normally present in food. Therefore, development of fast and sensitive detection technique is essential for accurate diagnosis of OTA. Currently, the most commonly used detection methods are enzyme-linked immune sorbent assays (ELISA) and chromatographic techniques. These techniques are sensitive but time consuming, and require expensive equipment, highly trained operators, as well as extensive preparation steps. These drawbacks limit their wide application in OTA detection. On the contrary, biosensors hold a great potential for OTA detection at for both research and industry because they are less expensive, rapid, sensitive, specific, simple and portable. This paper aims to provide an extensive overview on biosensors for OTA detection by highlighting the main biosensing recognition elements for OTA, the most commonly used nanomaterials for fabricating the sensing interface, and their applications in different read-out types of biosensors. Current challenges and future perspectives are discussed as well.

Microarray Profiling of Circular RNA Identifies hsa_circ_0126991 as a Potential Risk Factor for Essential Hypertension.

Essential hypertension (EH), a major cause of cardiovascular diseases, is an important public health issue. However, the molecular mechanisms involved in EH remain unknown. Circular RNA (circRNA) is a novel promising biomarker for the disease. The purpose of the present study was to determine the expression of circRNAs in the blood of EH patients and to evaluate the performance of circRNA for early diagnosis of EH. A total of 178 subjects were recruited in the case-control study. Initial screening was done by using the Agilent human circRNA microarray followed by qRT-PCR validation. Finally, miRNAs were combined with circRNAs to create a new early prediction model for EH. The expression level of hsa_circ_0126991 in EH patients was significantly higher in comparison with healthy controls (p < 0.0001). Using the interaction of miR-10a-5p in combination with hsa_circ_0126991 led to a sensitivity of 0.708, a specificity of 0.764, and combined area under the curve of 0.774 (95% CI: 0.705-0.843) for early diagnosis of EH. In summary, the present study uncovered a novel perspective that hyperexpression of hsa_circ_0126991 is correlated with the risk of EH and may serve as a stable biomarker for early diagnosis of EH.

Metabolomics workflow for lung cancer: Discovery of biomarkers.

Lung cancer is one of the most common cancers in the world. Due to the limitations of current diagnostic techniques and methods, most lung cancers are diagnosed at the advanced stage, which is not conducive to early treatment. The rise of metabolomics has provided new ideas for the early diagnosis of lung cancer. As a method for the comprehensive analysis of endogenous metabolites of the biological system, metabolomics has shown significant application potential for the early diagnosis and individualized treatment of various cancers including lung cancers. Via advanced analytical techniques and bioinformatics tools, the metabolome was excavated to find biomarkers related to cancer and its prognosis. In this review, the research methods and workflow of metabolomics are summarized, with an emphasis on the recent discovery of biomarkers and major metabolic pathways for lung cancers.

Chemical composition database establishment and metabolite profiling analysis of Yangyin qingfei decoction.

The chemical fingerprinting and metabolite profile in a rat plasma sample after intragastric administration of Yangyin qingfei decoction (YYQFD, 14 g/kg) were investigated. First, YYQFD was analyzed by UPLC/Q-TOF MS to establish the chemical composition database by comparing their retention behavior, accurate molecular mass and MS2 data with those of references or known compounds in the literature. In this database, 100 chemical constituents with information on retention time, molecular mass, molecular formula, MS2 data and compound name were identified, which can provide compound information for further metabolite profiling studies. Furthermore, 64 compounds including 37 prototypes and 27 metabolites were detected in the dosed rat plasma sample, and the metabolic pathways of YYQFD were hydrolyzation, hydroxylation, dehydrogenation, glucuronidation, glucosylation, sulfation and mixed modes. Among the five component herbs in the YYQFD, Glycyrrhizae Radix et Rhizome and Fritillariae Thunbergii bulbs were actively metabolized, contributing 16 and 7 metabolites, respectively. It is suggested that chemical characterization and metabolite profiling studies are valuable to elucidate the material basis of herbal preparations.

Ambient air pollution and risk of type 2 diabetes in the Chinese.

We performed a time series analysis to investigate the potential association between exposure to ambient air pollution and type 2 diabetes (T2D) incidence in the Chinese population. Monthly time series data between 2008 and 2015 on ambient air pollutants and incident T2D (N = 25,130) were obtained from the Environment Monitoring Center of Ningbo and the Chronic Disease Surveillance System of Ningbo. Relative risks (RRs) and 95% confidence intervals (95% CIs) of incident T2D per 10 µg/m3 increases in ambient air pollutants were estimated from Poisson generalized additive models. Exposure to particulate matter < 10 µm (PM10) and sulfur dioxide (SO2) was associated with increased T2D incidence. The relative risks (RRs) of each increment in 10 µg/m3 of PM10 and SO2 were 1.62 (95% CI, 1.16-2.28) and 1.63 (95% CI, 1.12-2.38) for overall participants, whereas for ozone (O3) exposure, the RRs were 0.78 (95% CI, 0.68-0.90) for overall participants, 0.78 (95% CI, 0.69-0.90) for males, and 0.78 (95% CI, 0.67-0.91) for females, respectively. Exposure to PM10 and SO2 is positively associated with T2D incidence, whereas O3 is negatively associated with T2D incidence.

Silver Doped Mesoporous Silica Nanoparticles Based Electrochemical Enzyme-Less Sensor for Determination of H2O2 Released from Live Cells.

In this study, a silver doped mesoporous silica nanoparticles-based enzyme-less electrochemical sensor for the determination of hydrogen peroxide (H2O2) released from live cells was constructed for the first time. The presented electrochemical sensor exhibited fast response (2 s) towards the reduction of H2O2 concentration variation at an optimized potential of -0.5 V with high selectivity over biological interferents such as uric acid, ascorbic acid, and glucose. In addition, a wide linear range (4 µM to 10 mM) with a low detection limit (LOD) of 3 µM was obtained. Furthermore, the Ag-mSiO2 nanoparticles/glass carbon electrode (Ag-mSiO2 NPs/GCE) based enzyme-less sensor showed good electrocatalytic performance, as well as good reproducibility, and long-term stability, which provided a successful way to in situ determine H2O2 released from live cells. It may also be promising to monitor the effect of reactive oxygen species (ROS) production in bacteria against oxidants and antibiotics.

Current issues facing the introduction of human papillomavirus vaccine in China and future prospects.

The introduction of human papillomavirus (HPV) vaccination in China aims to prevent HPV infection in all women. The issues that China might face include high cost of vaccines made in other countries, shortage in HPV vaccine supply, negative events attributed to vaccination (whether justified or not) that jeopardizes the general public's confidence in the HPV vaccine, cultural and literacy barriers, and sensitivity to receiving a vaccine for a sexually transmitted disease. Ensuring the effective delivery of the HPV vaccine in China, a country with vast economic, geographical, and cultural complexities, will require a commitment of significant resources. In light of the high price of imported vaccines, the availability of locally manufactured HPV vaccines would greatly facilitate the national HPV vaccination program. New evidence supporting the efficacy of a two-dose regime in younger adolescents would also be advantageous in terms of affordability and logistical simplicity of vaccine administration. Furthermore, it would potentially enhance the compliance and uptake, especially for hard to reach women in remote regions.

Genome-wide identification of the essential protein-coding genes and long non-coding RNAs for human pan-cancer.

MOTIVATION: Genome-scale CRISPR/Cas9 system has been a democratized gene editing technique and widely used to investigate gene functions in some biological processes and diseases especially cancers. Aiming to characterize gene aberrations and assess their effects on cancer, we designed a pipeline to identify the essential genes for pan-cancer. METHODS: CRISPR screening data were used to identify the essential genes that were collected from published data and integrated by Robust Rank Aggregation algorithm. Then, hypergeometrics test and random walks with restart (RWR) were used to predict additional essential genes on broader scale. Finally, the expression status and potential roles of these genes were explored based on TCGA portal and regulatory network analysis. RESULTS: We collected 926 samples from 10 CRISPR-based screening studies involving 33 different types of cancer to identify cancer-essential genes, which consists of 799 protein-coding genes (PCGs) and 97 long non-coding RNAs (lncRNAs). Then, we constructed a 'bi-colored' network with both PCGs and lncRNAs and applied it to predict additional essential genes including 495 PCGs and 280 lncRNAs on a broader scale using hypergeometrics test and RWR. After obtaining all essential genes, we further investigated their potential roles in cancer and found that essential genes have higher and more stable expression levels, and are associated with multiple cancer-associated biological processes and survival time. The regulatory network analysis detected two intriguing modules of essential genes participating in the regulation of cell cycle and ribosome biogenesis in cancer. AVAILABILITY AND IMPLEMENTATION: . SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.