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Background: Previous research has revealed that activation or aberrant expression of kinases can lead to tumorigenesis of various cancers, including neuroblastoma (NB). Suppression of kinase expression can reduce drug resistance. We explored the potential role and mechanism of the aurora kinase B (AURKB) gene in the acquisition of carboplatin resistance in NB.Methods: Immunohistochemistry (IHC) and qRT-PCR were used to explore the AURKB expression in NB patients. Subsequently, we structured Carboplatin-resistant NB cells. The potential biological functions of AURKB in carboplatin resistance were examined through knockdown of AURKB combined with CCK8, flow cytometry, immunohistochemistry, and western blot. Finally, overexpression of AURKB combined with ERK inhibitor (U0126) was carried out to explore the role of downstream signaling pathways.Results: Overexpression of AURKB was closely correlated to poor prognosis in NB patients. In vitro, knockdown of AURKB could lead to a decline in IC50 value and restrain the invasion and the expression of MRP1 and Ki67, while promotes apoptosis in carboplatin-resistant cells (IMR-32-R and SK-N-AS-R). Additionally, AURKB overexpression could potentiate the invasion and the expression of MRP1 and Ki67, while suppresses apoptosis in SK-N-AS-R and IMR-32-R, whereas ERK inhibitor U0126 could reverse the phenomenon caused by AURKB overexpression.Conclusion: AURKB overexpression was strongly associated with poor prognosis and carboplatin resistant acquisition. Additionally, suppression of AURKB-ERK axis might be a potential therapy for carboplatin resistance in NB patients.

Metabolic reprogramming has been suggested as a hallmark of cancer progression. Metabolomic analysis of various metabolic profiles represents a powerful and technically feasible method to monitor dynamic changes in tumor metabolism and response to treatment over the course of the disease. To date, numerous original studies have highlighted the application of metabolomics to various aspects of tumor metabolic reprogramming research. In this review, we summarize how metabolomics techniques can help understand the effects that changes in the metabolic profile of the tumor microenvironment on the three major metabolic pathways of tumors. Various non-invasive biofluids are available that produce accurate and useful clinical information on tumor metabolism to identify early biomarkers of tumor development. Similarly, metabolomics can predict individual metabolic differences in response to tumor drugs, assess drug efficacy, and monitor drug resistance. On this basis, we also discuss the application of stable isotope tracer technology as a method for the study of tumor metabolism, which enables the tracking of metabolite activity in the body and deep metabolic pathways. We summarize the multifaceted application of metabolomics in cancer metabolic reprogramming to reveal its important role in cancer development and treatment.

Research on the wettability of soft matter is one of the most urgently needed studies in the frontier domains, of which the wetting phenomenon of droplets on soft substrates is a hot subject. Scholars have done considerable studies on the wetting phenomenon of single-layer structure, but it is noted that the wetting phenomenon of stratified structure is ubiquitous in nature, such as oil exploitation from geological structural layers and shale gas recovery from shale formations. Therefore, the wettability of droplets on layered elastic gradient soft substrate is studied in this paper. Firstly, considering capillary force, elastic force and surface tension, the constitutive equation of the substrate in the vector function system is derived by using the vector function system in cylindrical coordinates, and the transfer relation of layered structure is obtained. Further, the integral expressions of displacement and stress of double Bessel function are given. Secondly, the numerical results of displacement and stress are obtained by using the numerical formula of double Bessel function integral. The results show that the deformation of the substrate weakens with the increase of the elastic modulus, also the displacement and stress change dramatically near the contact line, while the variation is flat when the contact radius is far away from the droplet radius.

There are approximately 20 million events of hepatitis E virus (HEV) infection worldwide annually. The genome of HEV is a single-strand, positive-sense RNA containing 5’ and 3’ untranslated regions and three open reading frames (ORF). HEV genome has 5’ cap and 3’ poly(A) tail to mimic host mRNA to escape the host innate immune surveillance and utilize host translational machineries for viral protein translation. The replication mechanism of HEV is poorly understood, especially how the viral polymerase distinguishes viral RNA from host mRNA to synthesize new viral genomes. We hypothesize that the HEV genome contains cis-acting elements that can be recognized by the virally encoded polymerase as “self” for replication. To identify functional cis-acting elements systematically across the HEV genome, we utilized an ORF1 transcomplementation system. Ultimately, we found two highly conserved cis-acting RNA elements within the ORF1 and ORF2 coding regions that are required for viral genome replication in a diverse panel of HEV genotypes. Synonymous mutations in the cis-acting RNA elements, not altering the ORF1 and ORF2 protein sequences, significantly impaired production of infectious viral particles. Mechanistic studies revealed that the cis-acting elements form secondary structures needed to interact with the HEV ORF1 protein to promote HEV replication. Thus, these cis-acting elements function as a scaffold, providing a specific “signal” that recruits viral and host factors to assemble the viral replication complex. Altogether, this work not only facilitates our understanding of the HEV life cycle and provides novel, RNA-directed targets for potential HEV treatments, but also sheds light on the development of HEV as a therapeutic delivery vector., Author summary Hepatitis E virus (HEV) is an underestimated pathogen, causing approximately 20 million infections worldwide annually and leading to about 60,000 deaths. There are no direct-acting antivirals for treating HEV, and although significant progress has been made to establish robust HEV cell culture models, the life cycle remains poorly characterized. A better understanding of HEV replication could facilitate the development of new drugs targeting this critical process. Our study found that RNA elements in the HEV genome interact with the HEV replicases to promote viral replication, suggesting that these RNA elements function as a scaffold for recruitment and assembly of the viral replication complex. This work furthers our understanding of HEV replication and could inform the generation of RNA-based therapeutics for treating HEV infection.

Objective The aim of the study was to explore the values and disadvantages of micromirror in the intracranial aneurysm clipping surgery. Methods Micromirror was used to assist microsurgical clipping to 36 intracranial aneurysms in 31 patients, of which 3 were carotid-ophthalmic artery aneurysms, 3 were anterior choroidal artery aneurysms, 11 were posterior communicating artery aneurysms, 7 were middle cerebral artery aneurysms, 10 were anterior communicating artery or anterior cerebral artery aneurysms, and the rest were a posterior cerebral artery aneurysm and a posterior inferior cerebellar artery aneurysm. The micromirror was used before and after clipping to observe the anatomic features of necks hidden behind and medial to aneurysms, to visualize surrounding neurovascular structures, and to verify the optimal clipping position. Intraoperative indocyanine green fluorescein angiography, postoperative computerized tomography angiography, and digital subtraction angiography confirmed the success of sufficient clipping. Results Intraoperative indocyanine green angiography, postoperative computerized tomography angiography , or digital subtraction angiography were performed and showed no case of wrong or insufficient clipping of aneurysm. Conclusions Micromirror-assisted microsurgical clipping to the intracranial aneurysm is safe, sufficient, convenient, and practical.

The true posterior communicating artery (PCoA) aneurysms in the distal portion of the posterior communicating artery are rare. The authors describe a 63-year-old woman with 1 true PCoA aneurysms in the distal portion of the PCoA, which was treated surgically through modified pterional approach. No neurologic deficit was present at the postoperative period. Although endovascular intervention is more and more widely used in the treatment of aneurysms, the authors have also emphasized that true PCoA aneurysms in the distal portion of the PCoA can also be surgically treated in suitable patients.

// Xingqiang Wang 1 , Enqin Wang 2 , Jun Cao 1 , Feng Xiong 1 , Yonglin Yang 1 and Haitao Liu 1 1 Department of Neurosurgery, Rizhao People’s Hospital, Jining Medical University, Rizhao 276826, Shandong, China 2 Clinical Skill Training Center, Rizhao People’s Hospital, Jining Medical University, Rizhao 276826, Shandong, China Correspondence to: Xingqiang Wang, email: wangxingqiangrz@163.com Keywords: MiR-145, ADAM19, GBM, EMT Received: August 02, 2017 Accepted: August 28, 2017 Published: September 30, 2017 ABSTRACT In recent years, increasing studies demonstrated that miR-145 plays a tumor suppressor role in many human cancers. In the present study, we evaluated the expression of miR-145 and A Disintegrin and Metalloproteinase 19 (ADAM19) in glioblastoma multiforme (GBM) tissues and cells. Furthermore, we investigated the mechanisms underlying miR-145/ADAM19-induced GBM biology. Here, we found that miR-145 expression was down-regulated, while ADAM19 expression was up-regulated in GBM tissues and cells. Moreover, miR-145 mimics repressed U87 and U251 cell proliferation, migration and invasion. miR-145 mimics also inhibited the epithelial-to-mesenchymal transition (EMT) of U87 and U251 cells. Mechanically, the 3’ untranslated region (3’-UTR) of ADAM19 mRNA was a direct target for miR-145. In addition, ADAM19 over-expression also partially abrogated miR-145-inhibited EMT. In conclusion, this work suggested that high miR-145 expression inhibited EMT of GBM cells by targeting ADAM19. Thus miR-145/ADAM19 can be suggested as a novel target for GBM patients.

Hepatitis E virus (HEV) causes predominantly acute and self-limiting hepatitis. However, in HEV-infected pregnant women, the case fatality rate because of fulminant hepatitis can be up to 30%. HEV infection is zoonotic for some genotypes. The HEV genome contains three open reading frames: ORF1 encodes the non-structural polyprotein involved in viral RNA replication, ORF2 encodes the capsid protein, ORF3 encodes a small multifunctional protein. Interferons (IFNs) play a significant role in the early stage of the host antiviral response. In this study, we discovered that the capsid protein antagonizes IFN induction. Mechanistically, the capsid protein blocked the phosphorylation of IFN regulatory factor 3 (IRF3) via interaction with the multiprotein complex consisting of mitochondrial antiviral-signaling protein (MAVS), TANK-binding kinase 1 (TBK1), and IRF3. The N-terminal domain of the capsid protein was found to be responsible for the inhibition of IRF3 activation. Further study showed that the arginine-rich-motif in the N-terminal domain is indispensable for the inhibition as mutations of any of the arginine residues abolished the blockage of IRF3 phosphorylation. These results provide further insight into HEV interference with the host innate immunity.

Neutrophil infiltration is frequently observed in lung cancer tissues. Extracellular RNAs (exRNAs) may facilitate tumor progression. The present study investigated the cross‑talk of tumor exRNAs and neutrophil extracellular traps (NETs) in lung cancer. Lewis lung carcinoma (LLC) cells were cultured with the deprived sera. And the cell culture supernatants (CCS) were analyzed in vitro and in vivo. The results revealed that exRNAs from lung cancer CCS promoted the inflammatory cytokine interleukin‑1β and reduced the vascular cell adhesion molecule‑1 expression in lung epithelial cells. Lung cancer CCS‑treated epithelial cells induced the production of NETs. By contrast, NETs reduced the tight junction protein claudin‑5 in epithelial cells. Furthermore, NETs caused the necrosis of epithelial cells, which resulted in the release of exRNAs. In mice, lung cancer cells instilled in the lung recruited neutrophils and initiated NETs. In patients with lung cancer, NETs were also observed. These results suggested that exRNAs in the cell culture supernatant may indirectly induce NETs and contribute to lung cancer oncogenesis.

Lung cancer is the leading cause of cancer-associated mortality. Tumor-associated neutrophils represent a large portion of inflammatory cells within the lung tumor microenvironment. However, the roles of neutrophil extracellular traps (NETs) in lung cancer remain unclear. In the present study, it was identified that Lewis lung carcinoma cells actively released the danger-associated molecular pattern protein high mobility group box 1 (HMGB1). Furthermore, HMGB1 in lung cancer cell supernatants promoted the formation of neutrophil extracellular traps (NETs), which was dependent on Toll-like receptor 4 (TLR4). The downstream molecules of TLR4, including myeloid differentiation factor 88, TIR-domain-containing adapter-inducing interferon-β, p38 mitogen-activated protein kinases (p38 MAPKs) and extracellular signal-regulated kinases (ERKs), were activated during the formation of NETs. In addition, inhibition of p38 MAPKs or ERKs significantly decreased NETs. Morphine, an additional ligand for TLR4, aggravated the NETs induced by lung cancer cells. The present study revealed novel mechanisms in tumor-associated NET formation.

Acute lung injury (ALI) is the leading cause of morbidity and mortality in critically ill patients. Neutrophil extracellular traps (NETs) have been well documented in the ALI model of bacterial infection. In the present study, we demonstrated that poly I:C could induce pulmonary NETs. Upon poly I:C intratracheal inoculation, neutrophil infiltration in the bronchoalveolar lavage fluid (BALF) was significantly increased. Furthermore, the inflammatory cytokines IL-1β, IL-6, and TNF-α in the lung were also significantly elevated. Neutrophil depletion abolished NETs and decreased both neutrophil infiltration and IL-1β in the lung. As expected, DNase I, an inhibitor of MPO and NADPH, decreased pulmonary inflammation and NETs. Blocking of the poly I:C receptor TLR3 reduced lung inflammation and NETs. The MAPK kinase inhibitor p38 diminished the formation of NETs and restored the expression of the tight junction protein claudin-5 in the mouse lung when challenged with poly I:C. In summary, poly I:C induced the formation of pulmonary NETs and ALI, which may be associated with the activation of p38 MAPK and the decreased expression of claudin-5.

The performances of advanced oxidation processes (AOPs) for the removal of refractory dissolved organic matter (DOM) are significantly different due to the various degradation mechanisms and competitive interactions between DOM and AOPs. This research traced the variation and removal of DOM components in tannery wastewater (TW) during conventional treatment, which includes coagulation, hydrolytic acidification/anoxic (H/A), and anaerobic/aerobic (A/O) stages. Electrochemical oxidation (EO) and ozone oxidation (OO) AOPs were conducted to treat a conventional treatment effluent based on selective oxidation and performance. The results demonstrated that the refractory DOM of the secondary effluent of the TW was mainly the hydrophilic neutrals (HIN) fraction (44.1%), which consisted of fatty acids and aliphatic compounds, and the hydrophobic acids (HOA) fraction (28.5%), which included the carboxylic-rich alicyclic molecules (CRAMs) and complex polycyclic aromatic structures. During the conventional treatment, lower molecular weight (MW) aliphatic and protein substances were preferentially removed by the H/A stage, while the A/O stage more completely eliminated hydrophobic aromatic substances of a lower MW. However, humus-like substances increased in both scenarios. With respect to the two AOPs, OO preferentially removed substances with a lower MW, and the HOA fraction converting to hydrophilic humus-like substances followed with more derived by-products. Comparing to OO, EO performed better on the removal of aromatic compounds, especially the humus-like substances (polycyclic aromatic and CRAM-like substances) in HOA fraction, therefore significantly improved the biodegradability of the effluent. The results indicate that EO has a better selectivity for humus-like substances and is suitable for the treatment of refractory DOM containing chloride.

Hepatitis B surface antigen (HBsAg) is the main diagnosis marker for hepatitis B virus (HBV) infection. In this study, a novel HBV mutant from an HBV-positive blood donor with false-negative results during HBsAg screening was identified. DNA sequencing discovered two mutations at nt 353 (A to T) and nt 349 (T to A), leading to Thr to Met and Ser to Thr substitutions at aa 118 and 117 of HBsAg, respectively. Further analysis showed that eight of ten HBsAg ELISA kits failed to detect this HBsAg mutant. A mutagenesis assay indicated that the Thr to Met substitution at aa 118 was the determinant for escape from HBsAg ELISA detection. A small-scale screening of blood donors identified two individuals infected by this unique HBV mutant, suggesting a certain level of prevalence among the general population. In conclusion, our study identified the aa 118 mutation in HBV surface antigen and provided information for improvement of HBV diagnosis products.

The present study analyzed the change of Toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) expression in focal cerebral ischemia-reperfusion injury model. A sample of 36 Sprague-Dawley rats were randomly selected and divided into sham operation group (group S), control group (group C) and Chrysanthemum ester group (NF-κB inhibitor, group CE), each group consisted of 12 rats. The rat model of focal cerebral ischemia-reperfusion was established. The physiological indexes and neurological severity score of rats was recorded by a double-blind method. The cerebral infarction area was evaluated by triphenyltetrazole oxide (TTC) staining on brain slices. Apoptosis was evaluated by TUNEL staining. Semi-quantitative PCR and western blot analysis was used to measure the expression of TLR4 and NF-κB. The neurological severity score of rats in group C and CE were found to be significantly lower than group S (P

Hepatitis E virus (HEV) is one of the viral pathogens causing hepatitis in humans. HEV open reading frame 3 (ORF3) encodes a small multifunctional protein (VP13), which is essential for HEV infection. In this study, a linear epitope was identified in a polyproline (PXXP) motif from VP13 of genotype 1 HEV by using a monoclonal antibody. The epitope was detected in enzyme-linked immunosorbent assay (ELISA), immunoblotting and immunofluorescence assays. Epitope mapping showed that the epitope locates in a proline-rich region containing a PXXP motif in amino acid residues 66-75 of VP13. The epitope was also detected in HEV-infected liver cells and reacted with genotype 1-specific antibodies in an HEV-positive human serum sample. The results demonstrated that the epitope in the PXXP motif of the genotype 1 VP13 is linear and surface-oriented, which should facilitate in-depth studies on the viral protein and HEV biology.

Career planning education is of great significance for college students to clear struggle target, enhance their employment ability, and it also promotes the quality of professional education. Whereas the existing career planning education modes for electric specialty student have the problems of lacking pertinence, lacking the whole process and unreasonable composition of the teaching staff. Therefore, according to the characteristics of electric specialty development, how to deepen the cooperation between school and enterprise, integrate the resources and establish the proper model of career planning education has become an urgent problem to be solved. Solving these probl ems will be important significance to guide the application talents in electric specialty.

Aim Although true posterior communicating artery (PCoA) aneurysms are rare, they are of vital importance. We reviewed 9 patients with this fatal disease, who were treated with endovascular embolization, and discussed the meaning of endovascular embolization for the treatment of true PCoA aneurysms. Material and methods From September 2006 to May 2012, 9 patients with digital substraction angiography (DSA) confirmed true PCoA aneurysms were treated with endovascular embolization. Patients were followed-up with a minimal duration of 17 months and assessed by Glasgow Outcome Scale (GOS) score. Results All the patients presented with spontaneous subarachnoid hemorrhage from the ruptured aneurysms. The ratio of males to females was 1:2, and the average age of onset was 59.9 (ranging from 52 to 72) years. The preoperative Hunt-Hess grade scores were I to III. All patients had recovered satisfactorily. No permanent neurological deficits were left. Conclusion Currently, endovascular embolization can be recommended as the top choice for the treatment of most true PCoA aneurysms, due to its advanced technique, especially the application of the stent-assisted coiling technique, combined with its advantage of mininal invasiveness and quick recovery. However, the choice of treatment methods should be based on the clinical and anatomical characteristics of the aneurysm and the skillfulness of the surgeon.

Background Selective pressure from either the immune response or the use of nucleoside analogs in antiviral therapy could be driving the emergence of HBV mutants. Because of the overlap of the open reading frame (ORF) S for the HBsAg and ORF P for viral polymerase, rtM204I and rtM204V mutations in the polymerase would produce sI195M and sW196S in the HBsAg. The combined effects of immune-escaped mutations (sT118M, sG145K, sG145R) and drug-resistant mutations (rtM204I, rtM204V) on the antigenicity profiles of HBsAg has not been widely explored. Methods To determine the combined effects of immune-escaped and drug-resistant mutants on the antigenicity profiles of HBsAg, recombinant plasmids encoding HBsAg double mutants were constructed using site-directed mutagenesis. The supernatant from each plasmid transfection was analyzed for HBsAg in the western-blotting and five of the most commonly used commercial ELISA kits in China. Results Western-blotting assay showed the successful expression of each HBsAg mutant. All five ELISA kits manifested similar avidity, which were demonstrated by the slope of the curves, for the sT118M mutant, and sT118M-rtM204I (sT118M-sI195M) and sT118M-rtM204V (sT118M-sW196S) double mutants, suggesting that drug-resistant YMDD mutants caused negligible losses in the antigenicity of immune-escaped sT118M HBsAg. In contrast, the presence of the rtM204I (sI195M) mutation, but not rtM204V (sW196S) in combination with the sG145K mutation significantly reduced the avidity of sG145K HBsAg. The rtM204I (sI195M) mutation also decreased the antigenicity profiles for sG145R HBsAg. Conclusions Drug-resistant mutations rtM204I (sI195M) and rtM204V (sW196S) caused significant reduction in antigenicity for the immune-escaped HBsAg mutants sG145K and sG145R, which may hamper HBV diagnosis and disease control from HBV blood-transfusion transmissions in China. The development of ELISA kits with a greater sensitivity for drug-resistant and immune-escaped HBsAg warrants further consideration.

Background In China, high prevalence of HBV and HCV parallels with the growing epidemic of syphilis and HIV in the general population poses a great threat to blood safety. This study investigated the prevalence of serologic markers for transfusion transmissible infections (TTIs) among four Chinese blood centers. Methods We examined whole blood donations collected from January 2000 through December 2010 at four Chinese blood centers. Post-donation testing of TTIs (HIV, HBV, HCV and syphilis) were conducted using two different enzyme-linked immunosorbent assay kits for each seromarker. The prevalence of serologic markers for TTIs (%) was calculated and additional analysis was conducted to examine donor characteristics associated with positive TTIs serology. Results Of the 4,366,283 donations, 60% were from first-time donors and 40% were from repeated donors. The overall prevalence of HIV, HBsAg, HCV and syphilis was 0.08%, 0.86%, 0.51% and 0.47%, respectively. The prevalence profile of TTIs varied among different blood centers and appeared at relatively high levels. Overall, the prevalence of HBsAg and HCV demonstrated a decline trend among four blood centers, while the prevalence of HIV and syphilis displayed three different trends: constantly steady, continually increasing and declining among different centers. Conclusions This study reflects the risk of TTIs has been greatly reduced in China, but blood transfusion remains an ongoing risk factor for the spread of blood-borne infections, and further work and improvements are needed to strengthen both safety and availability of blood in China.