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A $k$-tree is a spanning tree in which every vertex has degree at most $k$. In this paper, we provide a sufficient condition for the existence of a $k$-tree in a connected graph with fixed order in terms of the adjacency spectral radius and the signless Laplacian spectral radius, respectively. Also, we give a similar condition for the existence of a perfect matching in a balanced bipartite graph with fixed order and minimum degree., 12 pages

So far, there exist many publicly available palmprint databases. However, not all of them have provided the corresponding region of interest (ROI) images. If everyone uses their own extracted ROI images for performance testing, the final accuracy is not strictly comparable. Since ROI localization is the critical stage of palmprint recognition. The location precision has a significant impact on the final recognition accuracy, especially in unconstrained scenarios. This problem has limited the applications of palmprint recognition. However, many currently published surveys only focus on feature extraction and classification methods. Throughout these years, many new ROI localization methods have been proposed. In this chapter, we will group the existing ROI localization methods into different categories, analyze their basic ideas, reproduce some of the codes, make comparisons of their performances, and provide further directions. We hope this could be a useful reference for further research.

Introduction: Chlorfenapyr poisoning is uncommon, but fatal, and is often ignored. Chlorfenapyr inhibits ATP production in the mitochondrial of lipid-rich organs such as the brain. The initial symptoms of chlorfenapyr poisoning are not serious and are usually ignored; fever and unconsciousness are the main signs. Patients often die of brain damage, and survivors often present toxic leukoencephalopathy. Case report: We report a case of a 15-year-old female who swallowed 10 mL of 10%chlorfenapyr, and was subjected to gastric lavage one hour after ingestion. The patient felt no discomfort on the first and second day after lavage and went to school. On the third day, the patient complained of a headache and rested at home. On the fourth day, the patient still complained of headache, and the condition progressed to confusion and fever; therefore, the patient was admitted to the emergency room and underwent hemoperfusion. Cerebral CT revealed diffuse brain edema. The patient died on the fourth day because of central fever, brain hernia, and brain dysfunction. Conclusion: Chlorfenapyr poisoning is fatal, even in small doses. Patients suspected of chlorfenapyr poisoning should be closely observed and promptly treated by hemoperfusion.

An $[a,b]$-factor of a graph $G$ is a spanning subgraph $H$ such that $a\leq d_{H}(v)\leq b$ for each $v\in V(G)$. In this paper, we provide spectral conditions for the existence of an odd $[1,b]$-factor in a connected graph with minimum degree $\delta$ and the existence of an $[a,b]$-factor in a graph, respectively. Our results generalize and improve some previous results on perfect matchings of graphs. For $a=1$, we extend the result of O\cite{S.O} to obtain an odd $[1,b]$-factor and further improve the result of Liu, Liu and Feng\cite{W.L} for $a=b=1$. For $n\geq 3a+b-1$, we confirm the conjecture of Cho, Hyun, O and Park\cite{E.C}. We conclude some open problems in the end., Comment: 14 pages

Childhood maltreatment (CM) is regarded as an important risk factor for major depressive disorder (MDD). However, the neural links corresponding to the process of early CM experience producing brain alterations and then leading to depression later remain unclear. To explore the neural basis of the effects of CM on MDD and the potential role of microRNA-9 (miR-9) in these processes, we recruited 40 unmedicated MDD patients and 34 healthy controls (HCs) to complete resting-state fMRI scans and peripheral blood miR-9 tests. The neural substrates of CM, miR-9, and depression, as well as their interactive effects on intrinsic amygdala functional connectivity (AFC) networks were investigated in MDD patients. Two-step mediation analysis was separately employed to explore whether AFC strength mediates the association among CM severity, miR-9 levels, and depression. A support vector classifier (SVC) model of machine learning was used to distinguish MDD patients from HCs. MDD patients showed higher miR-9 levels that were negatively correlated with CM scores and depressive severity. Overlapping effects of CM, miR-9, and depressive severity on bilateral AFC networks in MDD patients were primarily located in the prefrontal-striatum pathway and limbic system. The connection of amygdala to prefrontal-limbic circuits could mediate the effects of CM severity on the miR-9 levels, as well as the impacts of miR-9 levels on the severity of depression in MDD patients. Furthermore, the SVC model, which integrated miR-9 levels, CM severity, and AFC strength in prefrontal-limbic regions, had good power in differentiating MDD patients from HCs (accuracy 85.1%). MiR-9 may play a crucial role in the process of CM experience-produced brain changes targeting prefrontal-limbic regions and that subsequently leads to depression. The present neuroimaging-epigenetic results provide new insight into our understanding of MDD pathophysiology.

In the multi-target TT&C system of relay satellite, due to the different distances between users and satellites, the strong signals of near users will restrain the weak signals of long-distance users and reduce the system capacity. This paper studies the power control algorithm in the reverse link of multi-target TT&C system. Specifically, the signal model of multi-target TT&C system is established, and two power adjustment algorithms, namely fixed step adjustment algorithm and adaptive step adjustment algorithm, are analyzed. The adaptive step adjustment algorithm is improved, and the upper limit of step adjustment is introduced. The simulation results show that the algorithm is effective in multi-target TT&C system.

Background: Breast cancer is the most common malignant tumor for women, which has been ranked first in women’ s cancer-related death. The objectives of the study are to uncover the underlying mechanisms of combination therapy of epirubicin with miR-17-5p in breast cancer. Methods: The expression levels of miR-17-5p were determined by quantitative RT-PCR. The survival rate of MCF-7 cell was detected respectively by MTT assay. The expression levels of miR-17-5p in MCF-7 cell was tested respectively with Ep via quantitative RT-PCR. miR-17-5p was to be transected with miR-17-5p mimic and negative control of miR-17-5p mimic (NC). Quantitative RT-PCR, MTT assay, flow cytometry assay, western blot for the proliferation and apoptosis related proteins were performed to determine the function of miR-17-5p in breast cancer cells. The bioinformatic programs TargetScan was used to predict the targets for miR-17-5p. Luciferase reporter gene assay system was used to validate and determine the targets of miR-17-5p. The relation between targets protein levels in breast cancer cells was investigated by western blot. Results: The expression levels of miR-17-5p was associated with the breast cancer tissues. The levels of miR-17-5p was down-regulated in breast cancer tissues and cells. Ep could inhibit viability of cancer cells in a concentration dependent manner and promote the expression of miR-17-5p in breast cancer cell lines. Over-expression of miR-17-5p induced cell apoptosis and upregulated the expression of p53, p21 and p27. miR-17-5p co-cultured with Ep is better than the other groups. The relative luciferase activity revealed that STAT3 was a potential target gene of miR-17-5p. Conclusions: Our work will prove that epirubicin regulated the expression of miR-17-5p to strengthen this effect of epirubicin and inhibited the progression of breast cancer.

Objective: To investigate variation in the characteristics of regional cerebral blood flow (rCBF), brain activity, and intrinsic functional connectivity (FC) across the Alzheimer's disease spectrum (ADS).Methods: The study recruited 20 individuals in each of the following categories: Alzheimer's disease (AD), mild cognitive impairment (MCI), subjective cognitive decline (SCD), and healthy control (HC). All participants completed the 3.0T resting-state functional MRI (rs-fMRI) and arterial spin labeling scans in addition to neuropsychological tests. Additionally, the normalized CBF, regional homogeneity (ReHo), and amplitude of low-frequency fluctuation (ALFF) of individual subjects were compared in the ADS. Moreover, the changes in intrinsic FC were investigated across the ADS using the abnormal rCBF regions as seeds and behavioral correlations. Finally, a support-vector classifier model of machine learning was used to distinguish individuals with ADS from HC.Results: Compared to the HC subjects, patients with AD showed the poorest level of rCBF in the left precuneus (LPCUN) and right middle frontal gyrus (RMFG) among all participants. In addition, there was a significant decrease in the ALFF in the bilateral posterior cingulate cortex (PCC) and ReHo in the right PCC. Moreover, RMFG- and LPCUN-based FC analysis revealed that the altered FCs were primarily located in the posterior brain regions. Finally, a combination of altered rCBF, ALFF, and ReHo in posterior cingulate cortex/precuneus (PCC/PCUN) showed a better ability to differentiate ADS from HC, AD from SCD and MCI, but not MCI from SCD.Conclusions: The study demonstrated the significance of an altered rCBF and brain activity in the early stages of ADS. These findings, therefore, present a potential diagnostic neuroimaging-based biomarker in ADS. Additionally, the study provides a better understanding of the pathophysiology of AD.

Purpose: The coronavirus disease 2019 (COVID-19) pandemic severely challenges public health and necessitates the need for increasing our understanding of COVID-19 pathogenesis, especially host factors facilitating virus infection and propagation. The aim of this study was to investigate key factors for cellular susceptibility to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection in the ocular surface cells. Methods: We combined co-expression and SARS-CoV-2 interactome network to predict key genes at COVID-19 in ocular infection based on the premise that genes underlying a disease are often functionally related and functionally related genes are often co-expressed. Results: The co-expression network was constructed by mapping the well-known angiotensin converting enzyme (ACE2), TMPRSS2, and host susceptibility genes implicated in COVID-19 genomewide association study (GWAS) onto a cornea, retinal pigment epithelium, and lung. We found a significant co-expression module of these genes in the cornea, revealing that cornea is potential extra-respiratory entry portal of SARS-CoV-2. Strikingly, both co-expression and interaction networks show a significant enrichment in mitochondrial function, which are the hub of cellular oxidative homeostasis, inflammation, and innate immune response. We identified a corneal mitochondrial susceptibility module (CMSM) of 14 mitochondrial genes by integrating ACE2 co-expression cluster and SARS-CoV-2 interactome. The gene ECSIT, as a cytosolic adaptor protein involved in inflammatory responses, exhibits the strongest correlation with ACE2 in CMSM, which has shown to be an important risk factor for SARS-CoV-2 infection and prognosis. Conclusions: Our co-expression and protein interaction network analysis uncover that the mitochondrial function related genes in cornea contribute to the dissection of COVID-19 susceptibility and potential therapeutic interventions.

Suicide ideation (SI) is a most high-risk clinical sign for major depressive disorder (MDD). However, whether the rich-club network organization as a core structural network is associated with SI and how the related neural circuits are distributed in MDD patients remain unknown. Total 177 participants including 69 MDD patients with SI (MDDSI), 58 MDD without SI (MDDNSI) and 50 cognitively normal (CN) subjects were recruited and completed neuropsychological tests and diffusion-tensor imaging scan. The rich-club organization was identified and the global and regional topological properties of structural networks, together with the brain connectivity of specific neural circuit architectures, were analyzed. Further, the support vector machine (SVM) learning was applied in classifying MDDSI or MDDNSI from CN subjects. MDDSI and MDDNSI patients both exhibited disrupted rich-club organizations. However, MDDSI patients showed that the differential network was concentrated on the non-core low-level network and significantly destroyed betweeness centrality was primarily located in the regional non-hub regions relative to MDDNSI patients. The differential structural network connections involved the superior longitudinal fasciculus and the corpus callosum were incorporated in the cognitive control circuit and default mode network. Finally, the feeder serves as a potentially powerful indicator for distinguishing MDDSI patients from MDDNSI or CN subjects. The altered rich-club organization provides new clues to understand the underlying pathogenesis of MDD patients, and the feeder was useful as a diagnostic neuroimaging biomarker for differentiating MDD patients with or without SI.

Melanoma is the most aggressive malignant tumor of skin cancer as it can grow rapidly and metastasize. Photodynamic therapy (PDT) is a promising cancer ablation method for skin tumors, although it lacks efficiency owing to factors such as tumor characteristics, delivery of photosensitizers, immune response in vivo etc. Extensive investigation of molecules that can potentially modulate treatment efficacy is required. Protein 4.1R is a cytoskeletal protein molecule. Previous studies have shown that protein 4.1R knockdown reduces PDT sensitivity in mouse embryonic fibroblast cells. However, the functional role of protein 4.1R in melanoma is unclear. In this study, we aimed to elucidate the effect of protein 4.1R on PDT for melanoma in mice and the mechanism of anti-tumor immunity. Our results indicated that CRISPR/Cas9-mediated protein 4.1R knockout promotes the proliferation, migration, and invasion of B16 cells. We further investigated the potential mechanism of protein 4.1R on tumor cell PDT sensitivity. Our results showed that protein 4.1R knockout reduced the expression of membrane transporters γ-aminobutyric acid transporter (GAT)-1 and (GAT)-2 in B16 cells, which affected 5-ALA transmembrane transport and reduced the efficiency of PDT on B16 cells. Protein 4.1R knockout downregulated the anti-tumor immune response triggered by PDT in vivo. In conclusion, our data suggest that protein 4.1R is an important regulator in PDT for tumors and may promote the progress and efficacy of melanoma treatment.

Uveal melanoma (UVM) is the most common primary intraocular human malignancy with a high mortality rate. Aberrant DNA methylation has rapidly emerged as a diagnostic and prognostic signature in many cancers. However, such DNA methylation signature available in UVM remains limited. In this study, we performed a genome-wide integrative analysis of methylome and transcriptome and identified 40 methylation-driven prognostic genes (MDPGs) associated with the tumorigenesis and progression of UVM. Then, we proposed a machine-learning-based discovery and validation strategy to identify a DNA methylation-driven signature (10MeSig) composing of 10 MDPGs (AZGP1, BAI1, CCDC74A, FUT3, PLCD1, S100A4, SCN8A, SEMA3B, SLC25A38 and SLC44A3), which stratified 80 patients of the discovery cohort into two risk subtypes with significantly different overall survival (HR = 29, 95% CI: 6.7–126, P

Objectives: To explore the role of medial collateral ligament repair in knee osteoarthritis based on TLR4/MyD88/NF-κ inflammatory signaling pathway. Methods: The modified Hulth method was used to establish models, which were divided into a repair group, a model group, and a sham operation group. The repair group was treated with medial ligament repair technology. Synovium and cartilage morphological changes were evaluated by hematoxylin-eosin staining to determine the degree of reparation. The cartilage was evaluated by the Mankin’s score, and inflammatory factors in cartilage tissues were determined by ELISA. The changes in TLR4, MyD88, and NF-κB levels were analyzed using the real-time quantitative PCR and Western blot assays. Results: The synovial and cartilage damages in the repair group and the sham operation group were significantly alleviated compared to the model group. The Mankin’s score of the model group was significantly lower than the other two groups. The expression of inflammatory factors in the repair group and the sham operation group were significantly lower than in the model group. The expressions of those factors in the repair group and the model group were higher than those in the model group. Conclusions: Medial ligament repair can improve the cartilage morphology and delay the development and progression of knee osteoarthritis by inhibiting the TLR4/MyD88/NF-κB signaling pathway.

The neural mechanisms underlying the polygenic effects of the endocytosis pathway on the brain function of Alzheimer's Disease (AD) remain unclear, especially in the prodromal stages of AD from early mild cognitive impairment (EMCI) to late mild cognitive impairment (LMCI). We used an imaging genetic approach to investigate the polygenic effects of the endocytosis pathway on the hippocampal network across the prodromal stages of AD. The subjects' data were selected from the Alzheimer's Disease Neuroimaging Initiative. Hippocampal volumes were examined in subjects of cognitive normal (CN), EMCI and LMCI groups. Multivariate linear regression analysis was employed to measure the effects of disease and endocytosis-based multilocus genetic risk scores (MGRS) on the hippocampal network which was constructed using the bilateral hippocampal regions. We identified hippocampal volumes in LMCI group were smaller than those in CN and EMCI groups. Endocytosis-based MGRS was widely influenced the neural structures within the hippocampal network, especially in the prefrontal-occipital regions and striatum. Compared to low endocytosis-based MGRS carriers, high MGRS carriers showed the opposite trajectory of hippocampal network functional connectivity (FC) across the prodromal stages of AD. Further, a model composed of selected hippocampal FCs and hippocampal volume yielded strong classification powers of EMCI and LMCI. These findings expand our understanding of the pathophysiology of polygenic effects underlying brain network in the prodromal stages of AD.

The Coronavirus disease 2019 (COVID-19) pandemic severely challenges public health and necessitates the need for increasing our understanding of COVID-19 pathogenesis, especially host factors facilitating virus infection and propagation. Here, the co-expression network was constructed by mapping the well-known ACE2, TMPRSS2 and host susceptibility genes implicated in COVID-19 GWAS onto a cornea, retinal pigment epithelium and lung. We found a significant co-expression module of these genes in the cornea, revealing that cornea is potential extra-respiratory entry portal of SARS-CoV-2. Strikingly, both co-expression and interaction networks show a significant enrichment in mitochondrial function, which are the hub of cellular oxidative homeostasis, inflammation and innate immune response. We identified a corneal mitochondrial susceptibility module (CMSM) of 14 mitochondrial genes by integrating ACE2 co-expression cluster and SARS-CoV-2 interactome. Gene ECSIT, as a cytosolic adaptor protein involved in inflammatory responses, exhibits the strongest correlation with ACE2 in CMSM, which has shown to be an important risk factor for SARS-CoV-2 infection and prognosis. Our co-expression and protein interaction network analysis uncover that the mitochondrial function related genes in cornea contribute to the dissection of COVID-19 susceptibility and potential therapeutic interventions.

Background Present study aims to longitudinal explore independent association of smoking status and cigarette consumption with general obesity and abdominal among Chinese adults by gender. Methods This study include 75,348 adults (35,907 males and 39,441 females) aged 18-65 years from the longitudinal data of China Health and Nutrition Survey (CHNS, 1991-2015). Multilevel mixed-effects linear and logistic regression models were performed for association analysis. Results Among males and females, heavy smokers (> 25 cigarette/d) increased from 5.5% and 0.05% in 1991 to 6.8% and 0.1% in 2015, respectively ( p < 0.001). After controlling for confounding factors, the net effect on male light (1–14 cigarette/d), moderate (15–24 cigarette/d), and heavy smokers was a significant decrease of 0.40 kg/m 2 (β: −0.40, 95% CI: − 0.48, −0.31), 0.51 kg/m 2 (β: −0.51, 95% CI: −0.60, −0.43), and 0.29 kg/m 2 (β: −0.29, 95% CI: −0.43, −0.14) in BMI, respectively. From moderate and light smokers to nonsmokers were linked with significant WC decreases of 0.87 cm (β: −0.87, 95% CI: −1.14, −0.58) and 0.86 cm (β: −0.87, 95% CI: −1.12, −0.59) in males and 1.58 cm (β: −1.58, 95% CI: −2.94, −0.22) and 1.37 cm (β: −1.37, 95% CI: −2.13, −0.59) in females, respectively. The odds ratio (95% CIs) for general obesity in males were 0.72 (0.65–0.81) for light smokers and 0.68 (0.61–0.76) for moderate smokers compared with nonsmokers. Similarly, the odds ratio (95% CIs) for abdominal obesity in males were 0.80 (0.76–0.86) for light smokers and 0.81 (0.76–0.87) for moderate smokers compared with nonsmokers. Moreover, the odds ratio (95% CIs) for abdominal obesity in females were 0.83 (0.71–0.98) for light smokers and 0.73 (0.58–0.91) for moderate smokers compared with nonsmokers.Conclusions Compared with nonsmokers, current smokers had lower BMI and WC among Chinese adults regardless of gender. Heavy smokers are more likely to be general obesity and abdominal obesity in male and abdominal obesity in female than other smokers. These findings may improve the understanding on how smoking behaviors affect fat distribution and provide scientific evidence regarding intervention in smoking and obesity by gender.

Background Altered structural and functional brain networks have been extensively studied in major depressive disorder (MDD) patients. However, whether the differential connectivity patterns in the rich-club organization, assessed from structural brain network analyses, and the associated connections of these regions are particularly susceptible to depression remain unclear. Methods We acquired resting-state functional magnetic resonance imaging (R-fMRI) and diffusion tensor imaging (DTI) from 31 unmedicated MDD patients and 32 cognitively normal (CN) subjects and completed a series of neuropsychological tests. Rich-club organization, network properties, and coupling between structural and functional connectivity (SC-FC) were explored. Furthermore, whether these indices could potentially deliver effective clinical predictive value for MDD patients were examined. Results The MDD patients showed disrupted structural rich-club organization and modularity, as well as a distinct correlation pattern between global efficiency and rich-club organization. Importantly, reduced SC-FC coupling, reflecting a decreased agreement in the integrity of the networks, was significantly associated with the strength of structural rich-club connections in the MDD patients. Furthermore, the disrupted structural rich-club organization, which was primarily located in the default mode network (DMN) and executive control network (ECN), emerged as a valuable indicator to distinguish between MDD and CN. Conclusions Findings of this study identified that the disrupted rich-club structural organization significantly influenced brain structural network modularity and integrity and could serve as a promising biological marker for the identification of MDD patients.

The application of TDRSS in TT&C of launch vehicle can improve the coverage and transmission rate of TT&C link. But the transmission protocol based on fixed transmission rate can not ensure the stable TT&C link based on TDRSS. The adaptive transmission protocol proposed in this paper can adjust the transmission rate according to the real-time transmission status during the whole flight. According to the different types of rocket-borne subscriber terminals, the open loop adaptive transmission protocol and closed loop adaptive transmission protocol are designed, which can both keep the stable transmission and improve the transmission efficiency.

In this study, we provided a detailed and comprehensive clinicopathological and pathogenic report of Bacillus endophthalmitis over the 8 years of the study period. We first reported the whole-genome sequence of Bacillus spp. causing devastating endophthalmitis and found that Bacillus toyonensis is able to cause endophthalmitis. Finally, we revealed significant endophthalmitis-associated virulence genes involved in hemolysis, immunity inhibition, and pathogenesis. Overall, as more sequencing data sets become available, these data will facilitate comparative research and will reveal the emergence of pathogenic “ocular bacteria.”, Bacillus endophthalmitis is a devastating eye infection that causes rapid blindness through extracellular tissue-destructive exotoxins. Despite its importance, knowledge of the phylogenetic relationships and population structure of intraocular Bacillus spp. is lacking. In this study, we sequenced the whole genomes of eight Bacillus intraocular pathogens independently isolated from 8/52 patients with posttraumatic Bacillus endophthalmitis infections in the Eye Hospital of Wenzhou Medical University between January 2010 and December 2018. Phylogenetic analysis revealed that the pathogenic intraocular isolates belonged to Bacillus cereus, Bacillus thuringiensis and Bacillus toyonensis. To determine the virulence of the ocular isolates, three representative strains were injected into mouse models, and severe endophthalmitis leading to blindness was observed. Through incorporating publicly available genomes for Bacillus spp., we found that the intraocular pathogens could be isolated independently but displayed a similar genetic context. In addition, our data provide genome-wide support for intraocular and gastrointestinal sources of Bacillus spp. belonging to different lineages. Importantly, we identified five molecular signatures of virulence and motility genes associated with intraocular infection, namely, plcA-2, InhA-3, InhA-4, hblA-5, and fliD using pangenome-wide association studies. The characterization of overrepresented genes in the intraocular isolates holds value to predict bacterial evolution and for the design of future intervention strategies in patients with endophthalmitis. IMPORTANCE In this study, we provided a detailed and comprehensive clinicopathological and pathogenic report of Bacillus endophthalmitis over the 8 years of the study period. We first reported the whole-genome sequence of Bacillus spp. causing devastating endophthalmitis and found that Bacillus toyonensis is able to cause endophthalmitis. Finally, we revealed significant endophthalmitis-associated virulence genes involved in hemolysis, immunity inhibition, and pathogenesis. Overall, as more sequencing data sets become available, these data will facilitate comparative research and will reveal the emergence of pathogenic “ocular bacteria.”

The turning points in international oil price are the most significant and sudden corrections in prices in the world market. Accurate prediction of turning points can help governments and enterprises develop effective oil reserve strategies and economic decisions. Nevertheless, forecasting the turning points poses great challenges in both methodology and computational effort. Log-periodic power law (LPPL) is one state-of-the-art method to predict turning points. In this research, we propose an improved version of LPPL forecasting model by incorporating a method called multi-population genetic algorithm (MPGA) to search for optimal values of parameters in the LPPL model. By doing so, the improved LPPL model provided significantly superior performance in predicting the turning points compared to prior researches. To verify the quality of the improved LPPL model, we collected the data of WTI spot price in the period starting from April 2003 to November 2016 and used the improved LPPL model to predict the three turning points in this period based on the data prior to the turning points. In addition, we compared the improved LPPL model with three LPPL models that use other approaches to search for parameters, including simulated annealing, standard genetic and particle swarm optimization. We showed that the results from our LPPL model are superior to other three search approaches. We also concluded that the fluctuation of the WTI (West Texas Intermediate) spot price in March 2017 is a false alarm of a major turning point. The improved LPPL has great potential to predict future turning points.

Blood-brain barrier (BBB) disruption is frequently observed in the glioma region. However, the tumor uptake of drugs is still too low to meet the threshold of therapeutic purpose. Method: A tumor vasculature-targeted nanoagonist was developed. Glioma targeting specificity of the nanoagonist was evaluated by in vivo optical imaging. BBB permeability at the glioma margin was quantitatively measured by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Single-photon emission computed tomography imaging/computed tomography (SPECT/CT) quantitatively determined the glioma uptake of the radiolabeled model drug. T2-weighted MRI monitored the tumor volume. Results: Immunostaining studies demonstrated that the BBB remained partially intact in the invasive margin of patients' gliomas regardless of their malignancies. DCE-MRI showed that vascular permeability in the glioma margin reached its maximum at 45 min post nanoagonist administration. In vivo optical imaging indicated the high glioma targeting specificity of the nanoagonist. SPECT/CT showed the significantly enhanced glioma uptake of the model drug after pre-treatment with the nanoagonist. Image-guided paclitaxel injection after nanoagonist-mediated BBB modulation more efficiently attenuated tumor growth and extended survival than in animal models treated with paclitaxel or temozolomide alone. Conclusion: Thus, image-guided drug delivery following BBB permeability modulation holds promise to enhance the efficacy of chemotherapeutics to glioma.

Heart failure (HF) is a major cause of death in cardiovascular diseases worldwide, and its molecular mechanisms and effective prevention strategies remain to be further studied. The myocardial cytoskeleton plays a pivotal role in many heart diseases. However, little is known about the function of the membrane cytoskeleton 4.1 protein family and related regulatory mechanisms in the pathogenesis of HF. In this study, we detected the localization and expression of the protein 4.1 family and ion channel proteins in a rat HF model induced by doxorubicin (DOX), and studied the interactions between them. Our results showed that compared with the control group, the HF group displayed an increased expression level of protein 4.1R and decreased levels of protein 4.1 G and 4.1 N. The Nav1.5 protein levels were significantly increased, while the SERCA2a and Cav1.2 protein levels were significantly decreased in the HF group. Furthermore, there is co-localization and interaction between protein 4.1R and Nav1.5, protein 4.1 G and SERCA2a, protein 4.1 N and Cav1.2, respectively. Taken together, the results indicated that the protein 4.1 family might be involved in the occurrence and development of HF through its interaction with ion channel proteins, suggesting that 4.1 proteins may serve as a novel therapeutic target for HF.

The application of TDRSS in the low orbit remote sensing satellites system can improve the effectiveness of remote sensing satellites. This paper built an evaluation system of remote sensing satellites from observation ability, response ability, data transmission ability and control ability. And linear weighting method was used for quantitative analysis of systematic contribution rate of TDRSS. As shown by the analysis result, TDRSS can improve the response ability, data transmission ability and control ability.

5-aminolevulinic acid (5-ALA)-based photodynamic therapy (PDT) has been successfully used in the treatment of cancers. However, the mechanism of 5-ALA transportation into cancer cells is still not fully elucidated. Previous studies have confirmed that the efficiency of 5-ALA-PDT could be affected by the membrane skeleton protein 4.1R. In this study, we investigated the role of 4.1R in the transport of 5-ALA into cells. Wild-type (4.1R+/+ ) and 4.1R gene knockout (4.1R-/- ) mouse embryonic fibroblast (MEF) cells were incubated with 1 mm 5-ALA and different concentrations of specific inhibitors of GABA transporters GAT (1-3). Our results showed that the inhibition of GAT1 and GAT2 in particular markedly attenuated the intracellular PpIX production, reactive oxygen species (ROS) level and 5-ALA-induced photodamage. However, the inhibition of GAT3 did not show such effects. Further research showed that 4.1R-/- MEF cells had a lower expression of GAT1 and GAT2 than 4.1R+/+ MEF cells. Additionally, 4.1R directly bound to GAT1 and GAT2. Taken together, GAT1 and GAT2 transporters are involved in the uptake of 5-ALA in MEF cells. 4.1R plays an important role in transporting 5-ALA into cells via at least partly interaction with GAT1 and GAT2 transporters in 5-ALA-PDT.

The accuracy of the baseline evaluation is of importance for calculating the transition enthalpy such as the latent heat of the crystallization. This study demonstrates the modified method of the equivalent non-latent heat baseline, by which the transition enthalpy can be measured accurately according to the transition peak in differential scanning calorimetric curve. With this method, the effect of melt superheating treatment time on the latent heat release upon the solidification of tin is investigated. The results show that the latent heat increases by increasing the treatment time, and is close to a constant when the treatment time is large enough, indicating the homogeneous system. And then, a simple model is established to describe the changes of the crystallization latent heat with the treatment time, which is confirmed by the experimental data of Sn.

Sol-gel method was used by taking tetraethyl orthosilicate (TEOS) as precursor, ethanol (C 2 H 5 OH) as solvent and hydrochloric acid (HCl) as catalyst, 1-γ-methacryloxypropyl trimethoxysilane (KH570) as a coupling agent for preparations of SiO 2 , KH570 and 9,10-Dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO, flame retardant) sols to improve flame retardancy and thermal stability of cotton fabrics. Dipping-baking process was used for finishing cotton fabrics. Surface morphology, surface functional group and element distribution, intrinsic crystal structure, pyrolysis characteristics and flame retardancy of cotton fabrics were characterized by Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), thermogravimetric analysis (TG), and limiting oxygen index (LOI). Results show that DOPO and SiO 2 sol have good synergistic flame retardant effect. Cotton fabric finished by hybrid sol of SiO 2 -KH570-DOPO has the best flame retardant effect, its LOI is 22.8 %, ΔLOI/Δm is 4.20 %/g. DOPO-contained hybrid sol can promote formation of three-dimensional microscopic gel coating and residual char in condensed phase.

Emerging evidence revealed the critical roles of long non-coding RNAs (lncRNAs) in maintaining genomic instability. However, identification of genome instability-associated lncRNAs and their clinical significance in cancers remain largely unexplored. Here, we developed a mutator hypothesis-derived computational frame combining lncRNA expression profiles and somatic mutation profiles in a tumor genome and identified 128 novel genomic instability-associated lncRNAs in breast cancer as a case study. We then identified a genome instability-derived two lncRNA-based gene signature (GILncSig) that stratified patients into high- and low-risk groups with significantly different outcome and was further validated in multiple independent patient cohorts. Furthermore, the GILncSig correlated with genomic mutation rate in both ovarian cancer and breast cancer, indicating its potential as a measurement of the degree of genome instability. The GILncSig was able to divide TP53 wide-type patients into two risk groups, with the low-risk group showing significantly improved outcome and the high-risk group showing no significant difference compared with those with TP53 mutation. In summary, this study provided a critical approach and resource for further studies examining the role of lncRNAs in genome instability and introduced a potential new avenue for identifying genomic instability-associated cancer biomarkers.

Protein 4.1R, an 80 000 MW membrane skeleton protein, is a vital component of the red blood cell membrane cytoskeleton that stabilizes the spectrin-actin network and regulates membrane properties of deformability and mechanical stability. It has been shown that 4.1R is expressed in T cells, including CD8+ T cells, but its role in CD8+ T cells remains unclear. Here, we have explored the role of 4.1R in CD8+ T cells using 4.1R-/- mice. Our results showed that cell activation, proliferation and secretion levels of interleukin-2 and interferon-γ were significantly increased in 4.1R-/- CD8+ T cells. Furthermore, the phosphorylation levels of linker for activation of T cells (LAT) and its downstream signaling molecule extracellular signal-regulated kinase were enhanced in the absence of 4.1R. In vitro co-immunoprecipitation experiments showed a direct interaction between 4.1R and LAT. Moreover, 4.1R-/- CD8+ T cells and mice exhibited an enhanced T-cell-dependent immune response. These data enabled the identification of a negative regulation function for 4.1R in CD8+ T cells by a direct association between 4.1R and LAT, possibly through inhibiting phosphorylation of LAT and then modulating intracellular signal transduction.

Protein 4.1R, an 80 000 MW membrane skeleton protein, is a vital component of the red blood cell membrane cytoskeleton that stabilizes the spectrin–actin network and regulates membrane properties of deformability and mechanical stability. It has been shown that 4.1R is expressed in T cells, including CD8(+) T cells, but its role in CD8(+) T cells remains unclear. Here, we have explored the role of 4.1R in CD8(+) T cells using 4.1R(−/−) mice. Our results showed that cell activation, proliferation and secretion levels of interleukin‐2 and interferon‐γ were significantly increased in 4.1R(−/−) CD8(+) T cells. Furthermore, the phosphorylation levels of linker for activation of T cells (LAT) and its downstream signaling molecule extracellular signal‐regulated kinase were enhanced in the absence of 4.1R. In vitro co‐immunoprecipitation experiments showed a direct interaction between 4.1R and LAT. Moreover, 4.1R(−/−) CD8(+) T cells and mice exhibited an enhanced T‐cell‐dependent immune response. These data enabled the identification of a negative regulation function for 4.1R in CD8(+) T cells by a direct association between 4.1R and LAT, possibly through inhibiting phosphorylation of LAT and then modulating intracellular signal transduction.

A pre-metastatic niche is a microenvironment prepared for the colonization of circulating tumor cells in specific organs. Exosomes are extracellular vesicles with a variety of biological functions. Exosomes play an irreplaceable role in the development of pre-metastatic niches, and mainly function as communication medium. In this review, we analyzed the effects of exosomes on pre-metastatic niches from various perspectives, including inflammation, immune response, angiogenesis, organotropism, matrix remodeling and biomarker expression. In particular, exosomes express programmed death ligand 1 (PD-L1) and cause the immune escape of tumor cells. The immunomodulatory effects of exosomes and their potential in liquid diagnosis have drawn our attention. The potential value of exosomes and pre-metastatic niches will be realized in the field of immunity therapy.

To explore the association of obesity indicators with hypertension and dyslipidemia in adults.The study used anthropometric data of 1022 adults aged 18-69 years in Liaoning, Henan and Hunan Provinces in 2012 to describe the overweight and obesity rate of body mass index( BMI), waist circumference( WC), waist to height ratio( WHtR), waist hip ratio( WHR) and body fat percentage( BF%). The ability of indicators to predict the risk of hypertension and dyslipidemia was evaluated by receiver operating characteristic( ROC) curve analysis.In comparison of anthropometric measurements, male WC was significantly higher than female, thigh circumference( ThC) was no gender differences and thigh height ratio( THtR) lower in men than in women. The obesity index was used to determine the overweight and obesity rate of Chinese adults: WHtRWHRBMIBF%WC was58. 7%, 50. 4%, 49. 1%, 35. 7% and 35. 3%, respectively. The obesity rate of BMI was13. 2%, significantly lower than other indicators. The ROC curve illustrated area under curve( AUC) of WHtR was the largest in predicting the risk of hypertension, and the cutoff values were 0. 53 and 0. 56 in male and female. AUC of WHR were the largest with hypercholesterolemia as dependent variables in male and female and as the only significant indicator in men. The value of BMI, WC, WHtR, WHR and BF% to predict the risk of hypertriglyceridemia was similar. ThC and THtR had a better prognosis value than BMI, WC, WHtR and other common indicators in low high-density lipoprotein cholesterolemia, especially in male residents. The cut-off values of ThC were 52. 50 and 55. 40, and the cut-off values of THtR were 0. 31 and 0. 35 in male and female.Men are more likely to hoard fat in the abdomen, female fat easily in the thigh accumulation. WHtR is the best index in predicting the risk of hypertension. The association between obesity indexes and different clinical classification of dyslipidemia are not the same: WHR shows the best effect in predicting the risk of hypercholesterolemia, BMI, WC, WHtR, WHR and BF% have the same value in predicting the risk of hypertriglyceridemia, ThC and THtR are better than BMI, WC, WHtR and other common indicators in predicting the risk of low high-density lipoprotein cholesterolemia, especially in male residents.

e21547 Background: Gene mutations in DNA damage repair (DDR) pathway were reported to affect the clinical response to immune checkpoint inhibitors (ICIs) by driving mutagenicity. Previous studies showed that RECQL5 is involved in RAD51-mediated strand invasion for homologous recombination DNA damage repair (HR-DDR). RECQL5 encoding RecQ protein-like 5 (RECQL5) is a member of RecQ helicase family and was discovered to play a tumor-suppressive or oncogenic role in various cancers. However, the association between RECQL5 mutation and ICI efficacy has not been revealed. Methods: Data of nine publicly independent cohorts of NSCLC, melanoma, and pan-cancer were retrieved (Rizvi, MSKCC, OAK/POPLAR, Van Allen, Hugo, Synder, Miao and Samstein cohorts) to investigate the correlation between RECQL5 mutations and clinical events including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and clinical benefit rate (CBR). Wilcoxon test was used for comparing tumor mutational burden (TMB) between RECQL5-mutated patients and their wild-type counterparts. In addition, the correlation between infiltration of immune cells and RECQL5 mutation status was also analyzed by QUANTISEO using data of SKCM cohort (n=466) from TCGA database. Statistical significance was set at P = 0.05. Results: RECQL5 mutations were most commonly seen in melanoma patients and the detection rate was 4%-8% in melanoma patients from cohort Van Allen, Hugo, Synder, and Miao. RECQL5 mutation was not detected in other cancers except for one lung cancer case. In the three melanoma cohorts (Van Allen, Synder, Miao) with OS data available, the OS of the RECQL5-mutated patients was 2 to 3 times longer than that of the RECQL5-wt patients. In Synder cohort, the difference in OS between these two subsets was statistically significant (53.9 months vs 25.0 months, P = 0.045). In addition, the occurrence of RECQL5 mutations was correlated with higher CBR both in Miao ( P = 0.017) and Synder cohorts ( P = 0.011). No difference was observed in the PFS or ORR between these two subsets. Notably, RECQL5 mutations were associated with higher TMB levels both in Miao (32.6 mut/Mb vs 7.9 mut/Mb, P = 0.016) and Synder cohorts (1124 mut/Mb vs 358 mut/Mb, P = 0.033). Moreover, RECQL5 mutations were found to be correlated with increased infiltration of CD4+ T cells (no-regulatory) ( P = 0.037), B cells ( P = 0.13) and decreased infiltration of regulatory CD4+ T cells ( P = 0.02) in RECQL5-mutated tumors over RECQL5-wt tumors. Conclusions: RECQL5 mutations can serve as a potential predictor for a durable response to ICIs in melanoma. Moreover, the occurrence of RECQL5 mutations was correlated with higher TMB level as well as infiltration of immune cells, indicating the underlying mechanism of its predictive effect.

e21596 Background: Melanoma is a serious skin cancer. Immune checkpoint inhibitors (ICIs) have shown durable responses and have been approved by FDA. However, ICIs demonstrate antitumor effects only in a fraction of patients, and research exploring the association between gene mutation and clinical benefit is limited. Mutations of PTPN11 (Protein Tyrosine Phosphatase, Non-receptor type11) have been reported to be associated with higher response rate and prolonged survival in advanced Renal Cell Carcinoma, Glioblastoma. The association between PTPN11 mutation and the efficacy of ICIs for melanoma is unknown. Methods: Genomic and survival data of melanoma patients administrated with ICIs were retrieved from publicly accessible data (Melanoma.Allen2015.WES.110) and the association between PTPN11 mutation and progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier curves and log-rank tests. At the same time，the association between PTPN11 mutation with TMB was also analyzed in this public immunotherapy-treated cohort(Melanoma.Allen2015.WES.110), Wilcoxon test was used for the comparison of TMB. In addition, Genomic, immune cell infiltration data of 466 patients with Skin Cutaneous Melanoma (SKCM) was obtained from The Cancer Genome Atlas (TCGA). The correlation analysis between immune cell infiltration and PTPN11 mutation status was further analyzed by CIBERSORT. Statistical significance was set at p = 0.05. Results: 3.6% (4/110) patients in the clinical cohort harbored PTPN11 mutation. Survival analysis in the public cohort demonstrated that PTPN11 mutation resulted in significantly longer OS (33.6 vs 8.5 months; HR, 0.16; p = 0.037) and an increasing trend on PFS without significantly difference (9.1 vs 2.8 months; HR, 0.3; P = 0.078) in melanoma patients treated with ICIs. Moreover, PTPN11 mutation is associated with higher TMB in public cohort (p = 0.01). Furthermore, the correlation analysis between immune infiltration and PTPN11 mutation status in melanoma shows that M1 macrophages increased significantly (p = 0.0014), CD8 T cells, plasma B cells and activated NK cells also show an upward trend (p = 0.17, p = 0.17 and p = 0.19) while the resting NK cells decreased significantly (p = 0.016)in melanoma patients with PTPN11 mutation. Conclusions: This study shows that PTPN11 mutation may serve as a potential positive biomarker of ICIs in melanoma since it relatively correlated with higher TMB. In addition, the up regulation of M1 macrophages and the down regulation of resting NK cells may be a potential mechanism for the better efficacy of ICIs in patients with PTPN11 mutation.

Wilms tumor (WT) is the most common cancer that primarily develops in abdominal solid organ of children. It has no incipient symptom, and the most frequent symptoms are a painless, palpable abdominal mass. Proteomics technology was used to select the differentially expressed proteins of bilateral Wilms tumor (BWT). Ten serum samples of children with BWT were chosen, 20 serum samples of children with unilateral WT (UWT) and 20 serum samples of healthy children were selected, and proteomics technology was used to detect and collect data. Using bioinformatics, the data were analyzed and 10 difference peaks were obtained (P

For patients with drug-resistant focal epilepsy, excision of the epileptogenic zone is the most effective treatment approach. However, the surgery is less effective in the 15-30% of patients whose lesions are not distinct when visualized by magnetic resonance imaging (MRI). Here, we show that an intravenously administered MRI contrast agent consisting of a paramagnetic polymer coating encapsulating a superparamagnetic cluster of ultrasmall superparamagnetic iron oxide crosses the blood-brain barrier and improves lesion visualization with high sensitivity and target-to-background ratio. In kainic-acid-induced mouse models of drug-resistant focal epilepsy, electric-field changes in the brain associated with seizures trigger breakdown of the contrast agent, restoring the T1-weighted magnetic resonance signal, which otherwise remains quenched due to the distance-dependent magnetic resonance tuning effect between the cluster and the coating. The electric-field-responsive contrast agent may increase the probability of detecting seizure foci in patients and facilitate the study of brain diseases associated with epilepsy.

Malignant gliomas are the most common primary brain tumors and are associated with aggressive growth, high morbidity, and mortality. Aberrant mesenchymal-epithelial transition factor (MET) activation occurs in approximately 30% of glioma patients and correlates with poor prognosis, elevated invasion, and increased drug resistance. Therefore, MET has emerged as an attractive target for glioma therapy. In this study, we developed a novel nanoinhibitor by conjugating MET-targeting cMBP peptides on the G4 dendrimer. Compared to the binding affinity of the free peptide (KD = 3.96 × 10–7 M), the binding affinity of the nanoinhibitor to MET increased 3 orders of magnitude to 1.32 × 10–10 M. This nanoinhibitor efficiently reduced the proliferation and invasion of human glioblastoma U87MG cells in vitro by blocking MET signaling with remarkably attenuated levels of phosphorylated MET (pMET) and its downstream signaling proteins, such as pAKT and pERK1/2. Although no obvious therapeutic effect was observed after tr...

To determine the optimal cut-off values of body fat percentage(BF%)in Chinese adults.A total of 1022 adults aged 18-69 years in Liaoning, Henan and Hunan Province was enrolled in this study. Analyzed the changes of BF%in different percentiles of body mass index(BMI), waist circumference(WC), waist-to-height ratio(WHtR), waist-to-hip ratio(WHR). BF%cut-off values were determined by receiver operating characteristic(ROC)curve.In Chinese adults, the average of BF%was 22. 1%in males and 33. 2%in females. The obesity prevalence determined by BF%cut-off points(recommended by WHO)was 31. 4%in men and 39. 3%in women. Taking hypertension as a dependent variable, ROC curve analysis showed that the optimal BF%cut-off value was 23. 2%(sensitivity:0. 61, specificity:0. 61)in men and 36. 4%(sensitivity:0. 48, specificity:0. 76)in women.In China, the optimal cut-off value of BF%in adult men is lower than the international standard, whereas the optimal cut-off value of BF%in adult women is higher than the international standard. It is of higher significance to make optimal BF%cut-off values for our own country.

To evaluate the usual fruit intake of Chinese adults.A total of 12 379 adults aged 18 to 65 years old with both 3 days 24 hours dietary recall data and FFQ data were chosen from China Nutritional Transition Cohort Study( 2015). The models of fruit consumption probability and amount for Chinese adults were fitted using the National Cancer Institute method( referred to as NCI), to evaluate the fruit usual intake of Chinese adults, and to describe the distribution of the consumption.According to 3 consecutive days of 24 hours dietary recall, the probability of consumption of fruit among Chinese adults was 40. 2%, the median of cosumption was 0( 0, 70. 0) g/d. The frequency of fruit consumption greater than or equal to once a day was17. 4% in male, which was lower than that of 22. 9% in female. According to the NCI method, the probability of fruit consumption among Chinese adults reached 98. 7%, the fruit consumption probability in male was 98. 3%, slightly lower than that of 99. 1% in female; the median of average daily consumption of fruit was 6. 4( 3. 2, 58. 3) g/d, it was4. 4( 2. 5, 36. 7) g/d in male, 9. 0( 4. 1, 78. 6) g/d in female.Through the NCI method, the rate of consumption of fruit among Chinese adults has been greatly improved. And the distribution of fruit consumption has been somewhat improved, but was still on the low level, far away from the lowest recommended intake. Some measures should be taken to guide reasonable fruit consumption behavior among Chinese residents. Meanwhile, by combining the FFQ method with dietary recall method, separating the nonconsumers from the un-consumers, and taking into account the correlation between fruit consumption probability and amount, NCI method can reevaluate the usual intake of fruits.

H9N2 subtype avian influenza viruses (AIVs) have been isolated from various species of wild birds and domestic poultry in the world, and occasionally transmitted to humans. Although H9N2 AIVs are seldom isolated from ostriches, seven such strains were isolated from sick ostriches in China between 2013 and 2014. Sequence analysis showed several amino acid changes relating to viral adaptation in mammals were identified. The phylogenetic analyses indicated that these isolates were quadruple reassortant viruses, which are different from the early ostrich isolates from South Africa or Israel. Most of the ostrich virus carried a human-type receptor-binding property. The chicken experiments showed the ostrich strains displayed low pathogenicity, while they could cause mild to severe symptoms in chicken. Theses strains could efficiently transmit among chickens, and one strain showed higher transmissibility. The virus could not kill mice, and merely replicated in the lung of mice. The ostrich strains could not efficiently transmit between guinea pigs in the direct contact model. These results suggested we should pay attention to the interface between ostrich and other domestic fowl, and keep an eye on this population when monitoring of influenza virus.

Suppose that the vertex set of a graph G is V ( G ) = { v 1 , ? , v n } . Then we denote by T r G ( v i ) the sum of distances between v i and other vertices of G . Let T r ( G ) be the n i? n diagonal matrix with its ( i , i ) -entry equal to T r G ( v i ) and D ( G ) be the distance matrix of G . Then L D ( G ) = T r ( G ) - D ( G ) is the distance Laplacian matrix of G . The distance Laplacian spectral radius of G is the spectral radius of L D ( G ) . In this paper we describe the unique graph with minimum distance Laplacian spectral radius among all connected bipartite graphs of order n with a given matching number and a given vertex connectivity, respectively.

Transcriptomic analyses have revealed an unexpected complexity in the eukaryote transcriptome, which includes not only protein-coding transcripts but also an expanding catalog of noncoding RNAs (ncRNAs). Diverse coding and noncoding RNAs (ncRNAs) perform functions through interaction with each other in various cellular processes. In this project, we have developed RAID (http://www.rna-society.org/raid), an RNA-associated (RNA–RNA/RNA–protein) interaction database. RAID intends to provide the scientific community with all-in-one resources for efficient browsing and extraction of the RNA-associated interactions in human. This version of RAID contains more than 6100 RNA-associated interactions obtained by manually reviewing more than 2100 published papers, including 4493 RNA–RNA interactions and 1619 RNA–protein interactions. Each entry contains detailed information on an RNA-associated interaction, including RAID ID, RNA/protein symbol, RNA/protein categories, validated method, expressing tissue, literature references (Pubmed IDs), and detailed functional description. Users can query, browse, analyze, and manipulate RNA-associated (RNA–RNA/RNA–protein) interaction. RAID provides a comprehensive resource of human RNA-associated (RNA–RNA/RNA–protein) interaction network. Furthermore, this resource will help in uncovering the generic organizing principles of cellular function network.

// Yali Zhong 1, 2, 3, 4 , Xiaoli Li 1 , Yasai Ji 1 , Xiaoran Li 3, 4 , Yaqing Li 1 , Dandan Yu 1 , Yuan Yuan 5 , Jian Liu 6 , Huixiang Li 7 , Mingzhi Zhang 1 , Zhenyu Ji 8 , Dandan Fan 8 , Jianguo Wen 9 , Mariusz Adam Goscinski 10 , Long Yuan 11 , Bin Hao 12 , Jahn M Nesland 3, 4 , Zhenhe Suo 1, 3, 4 1 Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China 2 Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China 3 Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, University of Oslo, Montebello, Oslo, Norway 4 Department of Pathology, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway 5 Department of Pathology, Capital Medical University, Beijing, China 6 Institute of Health Quarantine, Chinese Academy of Inspection and Quarantine, Beijing, China 7 Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China 8 Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 9 Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Henan, China 10 Department of Surgery, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway 11 Department of Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China 12 Department of Urology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China Correspondence to: Zhenhe Suo, email: zhenhes@medisin.uio.no Keywords: PDHA1, glycolysis, stemness, prostate cancer Received: September 30, 2016 Accepted: December 28, 2016 Published: January 05, 2017 ABSTRACT Cells generate adenosine-5′-triphosphate (ATP), the major currency for energy-consuming reactions, through mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis. One of the remarkable features of cancer cells is aerobic glycolysis, also known as the “Warburg Effect”, in which cancer cells rely preferentially on glycolysis instead of mitochondrial OXPHOS as the main energy source even in the presence of high oxygen tension. One of the main players in controlling OXPHOS is the mitochondrial gatekeeperpyruvate dehydrogenase complex (PDHc) and its major subunit is E1α (PDHA1). To further analyze the function of PDHA1 in cancer cells, it was knock out (KO) in the human prostate cancer cell line LnCap and a stable KO cell line was established. We demonstrated that PDHA1 gene KO significantly decreased mitochondrial OXPHOS and promoted anaerobic glycolysis, accompanied with higher stemness phenotype including resistance to chemotherapy, enhanced migration ability and increased expression of cancer stem cell markers. We also examined PDHA1 protein expression in prostate cancer tissues by immunohistochemistry and observed that reduced PDHA1 protein expression in clinical prostate carcinomas was significantly correlated with poor prognosis. Collectively, our results show that negative PDHA1 gene expressionis associated with significantly higher cell stemness in prostate cancer cells and reduced protein expression of this gene is associated with shorter clinical outcome in prostate cancers.