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Background: Nowadays, non-small cell lung cancer (NSCLC) is a common and highly fatal malignancy worldwide. Therefore, identifying the potential prognostic markers and therapeutic targets is urgent for patients. Objective: This study aimed at finding hub targets associated with NSCLC using multiple databases. Methods: Differentially expressed genes (DEGs) from Genome Expression Omnibus (GEO) cohorts were employed for the enrichment analyses of Gene Ontology (GO) terms and the Kyoto Encyclopedia of Genes and Genome (KEGG) pathways. Candidate key genes, filtered from the topological parameter 'Degree' and validated using the Cancer Genome Atlas (TCGA) cohort, were analyzed for their association with clinicopathological features and prognosis of NSCLC. Meanwhile, immunohistochemical cohort analyses and biological verification were further evaluated. Results: A total of 146 DEGs were identified following data preprocessing, and a protein-protein interaction (PPI) systematic network was constructed based on them. The top ten candidate core genes were further extracted from the above PPI network by using 'Degree' value, among which COL1A1 was shown to associate with overall survival (OS) of NSCLC as determined by using the Kaplan-Meier analysis (p=0.028), and could serve as an independent prognostic factor for OS in NSCLC patients (HR, 0.814; 95% CI, 0.665-0.996; p=0.046). We then analyzed the clinical stages, PPI, mutations, potential biological functions, and immune regulations of COL1A1 in NSCLC patients using multiple bioinformatics tools, including GEPIA, GeneMANIA, cBioPortal, GESA, and TISIDB. Finally, we further experimentally validated the overexpression of COL1A1 in NSCLC samples and found that inhibition of COL1A1 expression moderately sensitized NSCLC cells to cisplatin. Conclusion: Thus, our results showed that COL1A1 may serve as a potential prognostic marker and therapeutic target in NSCLC.

Large specific surface area and oxygen defects of metal oxides are the dominant factors to affect performances related to surface adsorption processes, and have been fully considered in the synthesis of materials. Understanding completely the effect of oxygen vacancies on the structure and the interaction with reactants is still under process. Here, for the first time, oxygen deficient two-dimensional (2D) oligo-layer molybdenum trioxide (MoO3-x) nanosheets with large aspect ratio of -670, were fabricated via a convenient microwave-assisted exfoliation method. The effect of oxygen vacancies on the surface adsorption of molecules was comprehensively investigated with experiments and DFT calculations. From the analysis of molecular dynamics and molecular electrostatic potential results, the enlarged interlayer spacings and oxygen vacancies working as the capture centers for negatively charged groups made 2D oligo-layer MoO3-x nanosheets promising for the adsorption for various organic molecules. Especially, a high value of -1290 mg/g rarely reported before was achieved for the adsorption of methylene blue. Benefited from the enlarged adsorption energies to gas molecules and the preferential adsorption of oxygen molecules in ambient atmosphere, p-type gas sensors based on 2D oligo-layer MoO3-x nanosheets were fabricated, which exhibited superior gas sensing performance to ethanol, acetone and hydrogen sulfide at room temperature. This work proposed an effective approach for synthesis of 2D nanomaterials, and underscored the importance of oxygen vacancies into 2D structures for different applications.

Osteosarcoma (OS), the most prevalent bone malignancy, mainly affects children and adolescents. Despite recent advances in multimodal therapy, the overall survival rate for OS patients remains poor. Chinese herb medicine (CHM) is an alternative therapeutic option for multifaceted diseases such as malignant tumors. For centuries in China, polygonum cuspidatum, a classic CHM, has been used to treat several diseases, nevertheless, the mechanisms underlying its therapeutic effects have not been fully elucidated. Through network pharmacology and bioinformatic tools, we evaluated the pharmacological activity of polygonum cuspidatum. We found that it has a potential therapeutic effect on malignant tumors, which was subsequently verified by intragastric administration of polygonum cuspidatum to OS cell xenografted mice models. Next, to establish the action mechanism of polygonum cuspidatum, we built a disease/drug-target PPI network that was made up of 250 core treatment targets against OS using Cytoscape software. Enrichment evaluation for the above targets indicated that polygonum cuspidatum may exert its effects on the cell cycle and apoptosis of OS cells through inhibiting Akt/ERK/EGFR pathways. Finally, the above in silico results were experimentally validated via a series of molecular biological and cell functional analyses. Taken together, the findings show that polygonum cuspidatum has a significant potential for OS treatment, which provides a novel insight into the discovery of CHM-based drug against malignancies. Abbreviations CC: Closeness centrality; OS: Osteosarcoma; TCM: Traditional Chinese medicine; NSCLC: Non-small cell lung cancer; DC: Degree centrality; CHM: Chinese herb medicine; BC: Betweenness centrality

Graphical abstract, Highlights • Three CHM components with the potential against COVID-19 are identified using TCMSP. • SPR assay result shows good binding affinity of puerarin and quercetin to ACE2. • Puerarin and quercetin impairs the binding of viral S-protein to ACE2 receptor. • Quercetin can also directly bind to S-protein to exert an viral neutralizing effect. • Results from this study propose a prompt application of puerarin on COVID-19 patients., The outbreak of COVID-19 raises an urgent need for the therapeutics to contain the emerging pandemic. However, no effective treatment has been found for SARS-CoV-2 infection to date. Here, we identified puerarin (PubChem CID: 5281807), quercetin (PubChem CID: 5280343) and kaempferol (PubChem CID: 5280863) as potential compounds with binding activity to ACE2 by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Molecular docking analysis showed that puerarin and quercetin exhibit good binding affinity to ACE2, which was validated by surface plasmon resonance (SPR) assay. Furthermore, SPR-based competition assay revealed that puerarin and quercetin could significantly affect the binding of viral S-protein to ACE2 receptor. Notably, quercetin could also bind to the RBD domain of S-protein, suggesting not only a receptor blocking, but also a virus neutralizing effect of quercetin on SARS-CoV-2. The results from network pharmacology and bioinformatics analysis support a view that quercetin is involved in host immunomodulation, which further renders it a promising candidate against COVID-19. Moreover, given that puerarin is already an existing drug, results from this study not only provide insight into its action mechanism, but also propose a prompt application of it on COVID-19 patients for assessing its clinical feasibility.

In this paper, we present a density-functional theory with a particle swarm optimisation algorithm to research the progress of the ligand effects of the gold (Au) structures and growth proc...

Background Colon cancer (CC) ranks the second highest mortality rate among malignant tumors worldwide, and the current mainstream treatment regimens are not very effective. The unique efficacy of Chinese herb medicine (CHM) for cancer has recently attracted increasing attention. Cinnamomi Ramulus (CR), as a classic CHM, has been widely used in the treatment of a variety of diseases for hundreds of years in China, but its specific pharmacological mechanism against CC needs to be fully evaluated. Methods TCMSP and China National Knowledge Infrastructure database were utilized to predict the candidate ingredients of CR, and TCMSP and SwissTargetPrediction database were also employed to predict the drug targets of the candidate ingredients from CR. We subsequently evaluated the therapeutic effect of CR by orally administrating it on CC-bearing mice. Next, we further identified the potential CC-related targets by using Gene Expression Omnibus (GEO) database. Based on these obtained targets, the drug/disease-target PPI networks were constructed using Bisogenet plugin of Cytoscape. The potential core therapeutic targets were then identified through topological analysis using CytoNCA plugin. GO and KEGG enrichment analyses were performed to predict the underlying mechanism of CR against CC. Furthermore, these in silico analysis results were validated by a series of cellular functional and molecular biological assays. UPLC–MS/MS method and molecular docking analysis were employed to identify the potential key components from CR. Results In this study, we firstly found that CR has potential therapeutic effect on cancer. Then, oral administration of CR could inhibit the growth of CC cells in C57BL/6 mice, while inhibiting the viability and motility of CC cells in vitro. We obtained 111 putative core therapeutic targets of CR. Subsequent enrichment analysis on these targets showed that CR could induce apoptosis and cell cycle arrest in CC cells by blocking Akt/ERK signaling pathways, which was further experimentally verified. We identified 5 key components from the crude extract of CR, among which taxifolin was found most likely to be the key active component against CC. Conclusions Our results show that CR as well as its active component taxifolin holds great potential in treatment of CC.

The blood–brain barrier (BBB) of Drosophila comprises a thin epithelial layer of subperineural glia (SPG), which ensheath the nerve cord and insulate it against the potassium-rich hemolymph by forming intercellular septate junctions (SJs). Previously, we identified a novel Gi/Go protein-coupled receptor (GPCR), Moody, as a key factor in BBB formation at the embryonic stage. However, the molecular and cellular mechanisms of Moody signaling in BBB formation and maturation remain unclear. Here, we identify cAMP-dependent protein kinase A (PKA) as a crucial antagonistic Moody effector that is required for the formation, as well as for the continued SPG growth and BBB maintenance in the larva and adult stage. We show that PKA is enriched at the basal side of the SPG cell and that this polarized activity of the Moody/PKA pathway finely tunes the enormous cell growth and BBB integrity. Moody/PKA signaling precisely regulates the actomyosin contractility, vesicle trafficking, and the proper SJ organization in a highly coordinated spatiotemporal manner. These effects are mediated in part by PKA’s molecular targets MLCK and Rho1. Moreover, 3D reconstruction of SJ ultrastructure demonstrates that the continuity of individual SJ segments, and not their total length, is crucial for generating a proper paracellular seal. Based on these findings, we propose that polarized Moody/PKA signaling plays a central role in controlling the cell growth and maintaining BBB integrity during the continuous morphogenesis of the SPG secondary epithelium, which is critical to maintain tissue size and brain homeostasis during organogenesis.

Patients with different karyotypes had different prognosis in t(8;21) acute myeloid leukemia (AML). Cytarabine (Ara-C) plays an important role as consolidation therapy in t(8;21) AML. T(8;21) AML patients with different karyotypes responded differently to post-remission therapy with Ara-C. However, the optimum dose of Ara-C in patients with different karyotypes remains unclear.From January 2002 to September 2018, a total of 188 younger adult (14-60 years) patients with t(8;21) AML were enrolled in this retrospective study. Cytogenetic analysis and aberration descriptions followed the International System for Human Cytogenetic Nomenclature. All the patients achieved first complete remission (CR1) after induction chemotherapy. Patients received low-dose Ara-C [LDAC (1 g/mThe results showed IDAC significantly improved OS compared with LDAC [hazard rate (HR) =0.55, P=0.0375] when the clinical factors were adjusted. However, no significant difference between HiDAC and IDAC was found. Subgroup analysis further showed that the OS advantage of IDAC was focused on patients with additional cytogenetic abnormalities, including loss of X chromosome (-X), del(9q), or complex karyotype (group B, HR =0.21, P=0.0125), but not on patients with t(8;21)-only or additional loss of Y chromosome (-Y) cytogenetics (group A, HR =0.77, P=0.4804) in multivariate analysis. Similarly, better OS was shown after IDAC than LDAC consolidation in patients in group B, whether they received allogeneic hematopoietic stem cell transplantation (allo-HSCT) or not, but not in group A.IDAC was suitable for patients with additional -X, del(9q), or complex karyotype, while LDAC might be sufficient for patients with t(8;21)-only or additional -Y cytogenetics. It suggested that t(8;21) AML patients with different karyotypes should use different consolidation regimens.

Lung cancer (LC) ranks the leading cause of cancer-related death worldwide, due partially to the unsatisfactory therapeutic effect of the mainstream treatment. Alternatively, Chinese herb medicine (CHM) offers a bright perspective for treating complex diseases. Mahuang Decoction (MHD), a classic CHM formula, has been widely used in treating respiratory diseases in China for centuries, but its action mechanism has yet to be fully investigated. In this study, we first systemically explore the action mechanism of MHD by using network pharmacology and bioinformatic analysis tools, which uncovered a potential “new use of old drug” for MHD in cancer treatment. The therapeutic effect of MHD on LC was then validated by oral administration of MHD in the immunodeficient mice bearing xenografted LC tumors. To better understand the pharmacological activity of MHD against LC, we next constructed a drug/disease-target PPI network composed of 252 putative core therapeutic targets of MHD using Cytoscape. The subsequent enrichment analysis for these targets suggested that MHD could affect the apoptosis and cell cycle of LC cells via impeding Akt/ERK signaling pathways. Notably, these in silico analysis results were further validated by a series of cellular functional and molecular biological assays. Thus, our results show that MHD holds a great potential in LC treatment.

The aberrant expression of long non-coding RNAs (lncRNAs) has been associated with a variety of malignancies, including colorectal cancer (CRC); however, the key lncRNAs associated with patient prognosis and their biological roles in CRC are yet to be determined. The aim of the present study was to determine the key lncRNAs associated with patient prognosis as well as their biological roles in CRC. Therefore, a dataset from The Cancer Genome Atlas containing the lncRNA expression data of 521 CRC and normal colorectal mucosal tissues, as well as the corresponding clinical data, were screened. A total of 1,180 significantly differentially expressed lncRNAs were associated with CRC as determined by t-tests in edgeR. Kaplan-Meier analysis revealed that 56 of the 1,180 lncRNAs were associated with overall survival (OS); 7 of the 56 lncRNAs were identified as key lncRNAs associated with the Tumor-Node-Metastasis stage of CRC by Kruskal-Wallis test. Subsequent univariate and multivariate Cox regression analyses of the 7 lncRNAs revealed 2 lncRNAs, DNAH17-AS1 and RP11-400N13.2, as potential independent prognostic factors for the OS of patients with CRC. Furthermore, the expression levelsof these 2 lncRNAs were significantly upregulated in CRC compared with those in normal tissues, which suggested that they may serve an oncogenic role in CRC. In addition, networks comprising the 2 lncRNAs and their respective co-expressed protein-coding genes (PCGs) were constructed using cor.test in R. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of these PCGs were conducted; DNAH17-AS1- and RP11-400N13.2-associated PCGs were reported to be involved in G-protein coupling-related functions. Thus, these independent prognostic lncRNAs and their associated functions identified in the present study may provide novel insight into potential prognostic biomarkers and therapeutic targets for the treatment of CRC.

Background The quantity of metastases lesions is an important reference when it comes to making a more informed treatment decision for patients with colorectal cancer liver metastases. However, the molecular alterations in patients with different numbers of lesions have not been systematically studied. Methods We investigated somatic alterations and microsatellite instability (MSI) of liver metastases from patients with single, multiple or diffuse metastasis lesions. A new algorithm “Pathway Damage Score” was developed to comprehensively assess the functional impact of somatic alterations at the pathway level. Pathogenic pathways of different metastasis were identified and their prognosis effects were evaluated. Furthermore, the subnetworks and affected phenotypes of the altered genes in each pathogenic pathway were analyzed. Results Somatic alterations and altered genes occurred sporadically as well as in MSI state in different metastasis types, although MSS patients had more metastatic lesions than that of the MSI patients. Every metastasis group has their own pathogenic pathways and damaged “Cargo recognition for clathrin‐mediated endocytosis” is significantly associated with poor prognosis (P

Synthetic two-dimensional (2D) materials without layered bulk allotropes are approaching a new frontier of materials flatland, one with properties richer than those of graphene-like materials. This is the case even as only a few chemical elements and blends have shown synthetic 2D forms. While hydrogen and metals are earth-abundant and form numerous compounds, rarely are 2D materials with only robust metal-hydrogen bonds. Here, a large new family of 2D materials is found from metal hydrides by high-throughput computational search augmented with first-principles calculations. There are 110 thermally and dynamically stable 2D materials that range from metallic materials to wide-gap semiconductors. A subgroup of these materials even varies from topological insulators to nodal-loop semimetals as well as from antiferromagnetic semiconductors to ferromagnetic half-metals. Unexpectedly, these monolayers resemble graphene in an ability to form weak interlayer interaction due to the variable multicenter bonding of hydrogen that eliminates the otherwise prevalent dangling bonds, rather than the covalent bonds between stacked layers as in previously reported synthetic 2D materials. This feature will favor potential experimental synthesis of these metal hydride monolayers.

Controllable creation of strain pattern in graphene's lattice is ideal for achieving intriguing pseudomagnetic field but remains challenging due to high in-plane stiffness of graphene. Using continuum theory and atomistic simulations, we show that carbon nanocones exhibit a peculiar electromechanical coupling that yields extreme pseudomagnetic fields by simple loads. Vertically pressing the nanocone by ∼2% creates well-defined strain pattern that leads electrons to behave as if under the influence of magnetic fields up to 600 Telsa. Moreover, the strain gradient can be tailored by varying the cone's geometry to achieve controlled distribution of pseudomagnetic fields over a large area. Since synthesis of nanocones of various materials has been mature, the proposed approach is further extendable to other two-dimensional materials towards their electronic modulation by inhomogeneous strain.

Ubiquitin‑conjugating enzyme E2C (UBE2C) is a key regulator of cell cycle progression, and its aberrant expression has been implicated in various malignancies. However, its clinical and biological roles in malignant melanoma is still unclear. In this study, we found a significant high expression level of UBE2C in melanoma by an in silico analysis of The Cancer Genome Atlas (TCGA) database, which was further validated using fresh melanoma samples. The KM plotter showed that UBE2C level was statistically related to the overall survival (OS) of melanoma patients (p

Two-dimensional boron (borophene) is featured by its structural polymorphs and distinct in-plane anisotropy, opening opportunities to achieve tailored electronic properties by intermixing different phases. Here, using scanning tunneling spectroscopy combined with first-principles calculations, delocalized one-dimensional nearly free electron states (NFE) in the (2,3) or \b{eta}12 borophene sheet on the Ag(111) surface were observed. The NFE states emerge from a line defect in the borophene, manifested as a structural unit of the (2,2) or \c{hi}3 sheet, which creates an in-plane potential well that shifts the states toward the Fermi level. The NFE states are held in the 2D plane of borophene, rather than in the vacuum region as observed in other nanostructures. Furthermore the borophene can provide a rare prototype to further study novel NFE behaviors, which may have potential applications on transport or field emission nanodevices based on boron., Comment: 4 figures

Rational design of noble catalysts with a potential to leverage efficiency at the atomic scale is vital for industrial applications. Such an ultimate atom-utilization efficiency can be achieved when all noble atoms exclusively contribute to catalysis. Here, we demonstrate a scalable synthesis of freestanding amorphous PtSex (where 1.2 x behaviors a fully-activated surface accessible to catalytic reactions. The catalytic performance of the amorphous layer is featured by a nearly 100% current density relative to a pure Pt surface and reliable production of sustained high-flux hydrogen over a 2-inch sized wafer sample as a proof-of-concept. Furthermore, an electrolyser using the PtSex amorphous layer as a cathode is demonstrated to generate a high current density of 1000 mA cm− 2. Such an amorphization strategy is potentially extendable to other noble metals, including Pd, Ir, Os, Rh, and Ru elements, demonstrating the universality of single-atom-layer catalysts.

Minichromosome maintenance proteins (MCMs) are considered to be essential factors coupling DNA replication to both cell cycle progression and checkpoint regulation. Previous studies have shown that dysregulation of MCMs are implicated in tumorigenesis of lung cancer. However, the distinct expression/mutation patterns and prognostic values of MCMs in lung cancer have yet to be systematically elucidated. In the present study, we analyzed the transcriptional levels, mutations, and prognostic value of MCM1-10 in non-small cell lung cancer (NSCLC) patients using multiple bioinformatics tools, including ONCOMINE, GEPIA, Kaplan–Meier Plotter, cBioPortal, and GESA. The analysis results from GEPIA dataset showed that MCM2/4/10 was significantly high expressed in both lung adenocarcinoma (LUAD) and squamous cell lung carcinomas (LUSCs). Meanwhile, the expression levels of MCM2/4/6/7/8 were associated with advanced tumor stages. Subsequent survival analysis using the Kaplan–Meier Plotter indicated that high expression levels of MCM1/2/3/4/5/6/7/8/10 were associated with worse overall survival (OS), while high expression level of MCM9 predicted better OS in these patients. Furthermore, we experimentally validated overexpression of MCM2 and MCM4 in NSCLC, thus the results from this study support a view that they may serve as potential prospective biomarkers to identify high-risk subgroups of NSCLC patients.

Due to its in-plane structural anisotropy and highly polymorphic nature, borophene has been shown to form a diverse set of linear superlattice structures that are not observed in other two-dimensional materials. Here, we show both theoretically and experimentally that concentric superlattice structures can also be realized in borophene via the energetically preferred self-assembly of coherent twin boundaries. Since borophene twin boundaries do not require the creation of additional lattice defects, they are exceptionally low in energy and thus easier to nucleate and even migrate than grain boundaries in other two-dimensional materials. Due to their high mobility, borophene twin boundaries naturally self-assemble to form novel phases consisting of periodic concentric loops of filled boron hexagons that are further preferred energetically by the rotational registry of borophene on the Ag(111) surface. Compared to defect-free borophene, concentric superlattice borophene phases are predicted to possess enhanced mechanical strength and localized electronic states. Overall, these results establish defect-mediated self-assembly as a pathway to unique borophene structures and properties.

Ligand-protected gold clusters are widely used in biosensors and catalysis. Understanding the structural evolution of these kinds of nanoclusters is important for experimental synthesis. Herein, ba...

The nuclei and the formation mechanism of chiral carbon nanotubes, namely, single-, double-, and triple-walled carbon nanotubes are simulated by the first principle density functional theory. The formation mechanism from nuclei to corresponding infinitely long carbon nanotubes occurs spirally and via absorbing carbon atoms layer by layer. Carbon atoms at the open end are metastable state compared with ones in the tube wall or the closed end, which indicate the growth point of chiral carbon nanotubes is located at the open end. Growth of outer layer tubular clusters takes precedence over the inner layer in the process of forming multi-walled nuclear structures. Because of the ratio of carbon atoms at the open end to all carbon atoms decreases, the stability of the tubular clusters increases with their length. The infinitely long carbon nanotubes are obtained by executing periodic boundary conditions depend on corresponding nuclear structures.

Using special metal clusters (superatoms) as superatomic building blocks for hierarchically assembled materials allows these properties to be incorporated into designer materials with tailored properties. But how to assemble the superatoms to form materials is a critical problem, and no clear understanding until now. The assembly of the superatoms is basically equivalent to superatoms stacking. So, can superatoms, like atoms, form crystal by a particular chemical bond? How to bond between superatoms? Are there any strategy models for superatom assembly? To answer those questions, a phenomenological theory named the superatomic molecule theory is introduced which contains understandings of the chemical bonds between superatoms, the building blocks and the assembly strategies. The chemical bonds between the superatoms can be classified into three types, including the super covalent bond, the super hybrid bond and the super non-bonding. A new perspective for the building blocks named isospueratom is introduced, which point out that the isomers of the superatoms can be chosen indiscriminately as building blocks. In addition to assembling superatoms by super valence bonds, other two superatom assembly strategies named superatom network and hybrid superatom network are included. In summary, the superatomic molecule theory contains the understanding of the bonds between superatoms, the thinking of the building blocks, and the consideration on strategies of the superatom assembly. The superatomic molecule theory cannot only be used as the theoretical basis of the superatom assembly, but also be used to understand the stabilities of some special cluster, and provides theoretical guidance for the new clusters design and synthesis.

Double-crown Ni, Pd, or Pt nanoclusters have attracted extensive interests due to their aesthetic structure and intriguing properties. However, their doping by other metals remains unknown until now. Herein, Pd4 (PET)8 and Pd5 (PET)10 (PET: SCH2 CH2 Ph) were successfully doped with gold and the doped nanoclusters were characterized by using multiple techniques such as mass spectrometry and X-ray crystallography. It is revealed that in the doping not one but two gold atoms replace one Pd with the other double-crown structure essentially unchanged, and the gold-doping results in the blue-shift of the maximum visible absorption, the increase of optical energy gap and the reduction of anti-aromaticity of monometal Pd nanoclusters. Importantly, it is found that Au4 Pd2 (PET)8 nanocluster bears chirality originating from not only the helixed Au4 Pd2 S8 framework, but also unanimous R or S configuration of sulfur atoms in the enantiomer. For the latter chirality origin, it was not previously reported or proposed. Au4 Pd2 (PET)8 reported here also represents the smallest chiral bimetal nanocluster so far to the best of our knowledge. This work advances one step toward both the tailoring of group 10 metal nanoclusters by doping and the understanding of chirality origin for metal nanoclusters.

Target-coordinate transformation in the lidar spot of the down-looking synthetic-aperture imaging lidar (SAIL) was performed, and the attitude errors were deduced in the process of imaging, according to the principle of the airborne down-looking SAIL. The influence of the attitude errors on the imaging quality was analyzed theoretically. A compensation method for the attitude errors was proposed and theoretically verified. An airborne down-looking SAIL experiment was performed and yielded the same results. A point-by-point error-compensation method for solving the azimuthal-direction space-dependent attitude errors was also proposed.

Circulating tumor cells (CTCs) are used for metastasis surveillance in cancer patients, but low detection rates limit their use in colorectal cancer (CRC). We investigated the distribution of CTCs in peripheral and portal blood of CRC patients, and analyzed the relationship between serum tumor CEA/CA19-9 markers and CTCs blood levels. CTC levels detected in first reflux/portal vein blood were higher than in peripheral blood, and liver reduced CTCs amount. CTCs-positive patients had increased serum CEA and CA 19-9 levels, and the CEA and CA 19-9 levels correlated with the CTCs levels. Even in non-metastatic CRC patients with barely detectable CTCs in peripheral blood, serum CA 19-9 levels correlated with the CTC levels in first reflux/portal vein blood. These results demonstrate that CTC detection in the first reflux vein/portal vein blood is more sensitive than in peripheral blood, suggesting that clinical diagnosis using the CellSearch System should be based on the CTC detection in first reflux vein blood due to the high detection rates. In addition, our results indicate that serum CA 19-9 levels may serve as a diagnostic marker for further evaluation of CTC levels in portal blood.

// Bowen Ding 1, * , Xujie Gao 1, * , Hui Li 1 , Liren Liu 1 , Xishan Hao 1 1 Department of Gastrointestinal Cancer Biology, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China * These authors contributed equally to this work Correspondence to: Liren Liu, email: liuliren@tjmuch.com Xishan Hao, email: haoxishan@tjmuch.com Keywords: miRNA signature, prognostic biomarkers, overall survival, stomach adenocarcinoma Received: November 10, 2016 Accepted: February 22, 2017 Published: March 07, 2017 ABSTRACT Recent microRNA (miRNA) expression profiling studies suggest the clinical use of miRNAs as potential prognostic biomarkers in various malignancies. In this study, aiming to identify microRNAs with prognostic value for overall survival (OS) in stomach adenocarcinoma (STAD) patients, we analyzed the miRNA expression profiles and the associated clinical characteristics in 380 STAD samples from The Cancer Genome Atlas (TCGA) dataset. An eight-miRNA signature for predicting OS in STAD patients was identified and self-validated by survival analysis and semi-supervised principal components method. We developed a linear prognostic model composed of these miRNAs to divide patients into high- and low-risk groups according to the calculated prognostic scores. Kaplan-Meier analysis demonstrated that patients in the high-risk group had worse OS compared with patients in the low-risk group. Notably, this miRNA prognostic model showed prognostic significance to the STAD patients in early stages and the chemo-resistant patients, who would potentially benefit from additional medical interventions. Finally, this eight-miRNA signature is an independent prognostic biomarker and demonstrates a good predictive performance for 5-year survival. Thus, this signature may serve as a novel biomarker for predicting survival as well as chemotherapy response in STAD patients.

// Rupeng Zhang 1, 4, 5 , Yuenan Guo 1, 4, 5 , Zhenchi Ma 1, 4, 5 , Gang Ma 2, 4, 5 , Qiang Xue 1, 4, 5 , Fangxuan Li 3, 4, 5 , Liren Liu 2, 4, 5 1 Department of Gastric Cancer Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China 2 Department of Gastrointestinal Cancer Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China 3 Department of Cancer Prevention Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China 4 National Clinical Research Center of Cancer, Tianjin 300060, China 5 Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China Correspondence to: Rupeng Zhang, email: tijzhangrp@163.com Liren Liu, email: liuliren@tjmuch.com Keywords: PTENP1, miR-106b, miR-93, long non-coding RNA, gastric cancer Received: October 20, 2016 Accepted: January 29, 2017 Published: February 13, 2017 ABSTRACT Recent studies have shown that competing endogenous RNAs (ceRNAs) play an important role in the regulation of gene expression, and participate in a wide range of biological processes, including carcinogenesis. Long non-coding RNA PTENP1, the pseudogene of PTEN tumor suppressor, has been reported to exert its tumor suppressive function via modulation of PTEN expression in many malignancies. However, whether a PTENP1~miRNA~PTEN ceRNA network exists and how it functions in gastric cancer (GC) remains elusive. In order to identify and characterize the PTENP1~miRNA~PTEN ceRNA network in GC, we first determined PTENP1 levels in clinical GC samples and found that PTENP1 and PTEN were concurrently downregulated in these samples. We further demonstrated that PTENP1 could act as a ceRNA to sponge miR-106b and miR-93 from targeting PTEN for downregulation using a novel ceRNA in vitro gradient assay. Thus, we revealed a tumor suppressive role of PTENP1 as ceRNA in GC and pinpointed the specific miRNAs decoyed by PTENP1, highlighting the emerging roles of ceRNAs in the biological regulation of GC cells and their possible clinical significance.

Revealing the stability and structural patterns is important for precisely synthesizing or assembling ligand protected nanoclusters, and even their applications as functional nanomaterials. Investigations on structural evolutional patterns and structural stability are very challenging, because structures change with the nanocluster size and the structural stability depends on both the electron structures of cores and ligand type. Herein, we propose a hybrid superatom network (hSAN) model to understand the stability of some gold nanoclusters with different kinds of ligands. In this model, 4c-2e superatom Au4 can form conjugated superatom networks by vertex sharing, and ligands further connect the conjugated superatom networks together to form a bigger complex network, i.e. a hSAN. The stability of the clusters, including [Au24(CCPh)14(PPh3)4]2+, Au28(S-c-C6H11)20, Au36(SCH2Ph-tBu)8Cl20, Au40(O-MBT)24 and Au52(TBBT)32 can be explained uniformly by the hSAN model. Beyond that, a new heuristic structural pattern named the Au13 topological rule is proposed. In the light of this heuristic rule, every Au7 bi-tetrahedral kernel is included in an Au13 structure with quasi-Oh symmetry, i.e. as long as the Au7 bi-tetrahedral kernel is formed, it will be surrounded by six Au atoms to form an Au13 structure topologically. According to this understanding, a new nanocluster [Au44(CCH3)26(PCH3)4]2+ and a new nanowire with the structural evolutional formula [Au(20n+4)(CCH3)(12n+2)(PCH3)4]2+ (n = 1, 2, 3, 4, …) are predicted. Both the understanding of the stability and the structure rule are free from the type of ligand, and will be useful for the structural predictions and determinations of ligand protected gold nanoclusters.

As a popular Chinese herbal medicine (CHM), polygonum cuspidatum is widely used to treat various diseases in China. However, its biological function and action mechanism have yet to be systematically explored. In the present study, we first identified 14 potential active ingredients of polygonum cuspidatum using the TCMSP server and then conducted an in silico target prediction for these ingredients using PharmMapper. The subsequent KEGG pathway enrichment analysis of the 57 identified potential targets revealed that they were closely associated with cancer and gynecological disorders. Furthermore, a protein-protein interaction network of these targets was constructed using STRING and Cytoscape, through which 11 core targets were excavated according to degree, a key topological parameter. Meanwhile, we developed a novel formula, in which the “R value” is determined by average shortest path length and closeness centrality, two other key topological parameters, to evaluate the reliability of these predicted core targets. Intriguingly, among the top 10 core targets excavated using this new formula, 7 overlapped with the former 11 core targets, showing a good consistency in these core targets between the different prediction algorithms. Next, 7 ingredients were identified/validated from the crude extract of polygonum cuspidatum using UPLC-MS/MS. Noteworthy, 6 potential targets predicted for these 7 ingredients overlapped with the 7 core targets excavated from the previous in silico analyses. Further molecular docking and druggability analyses suggested that polydatin may play a pivotal role in manifesting the therapeutic effects of polygonum cuspidatum. Finally, we carried out a series of cell functional assays, which validated the anti-proliferative effects of polygonum cuspidatum on gynecological cancer cells, thus demonstrating our network pharmacology approach is reliable and powerful enough to guide the CHM mechanism study.

Hypopharynx carcinoma tends to be diagnosed at advanced stage and usually has a poor prognosis because of the high incidence of submucosal spreading and lymphatic metastasis. Total pharyngolaryngoesophagectomy (PLE) is mostly used as a curative intervention for this deadly disease, and a commonly used reconstruction method after PLE is gastric pull-up, which could be further divided into tubular gastric pull-up and whole gastric pull-up procedures. Aiming to achieve a precise guidance on optimal reconstruction method after PLE, the present study evaluated the postoperative complications involving in different gastric pull-up procedures in patients with hypopharynx cancer. A total of 52 consecutive patients with hypopharyngeal cancer who underwent total PLE with gastric pull-up reconstruction in Tianjin Medical University Cancer Institute and Hospital between 1996 and 2014 were analyzed in this study. Of these patients, 28 underwent tubular gastric pull-up reconstruction procedure (Group A), whereas 24 underwent whole gastric pull-up reconstruction procedure (Group B). We compared the postoperative complications between these two groups retrospectively. Postoperative anastomotic fistulas occurred in three patients in Group A (3/28)

A static-mode synthetic aperture imaging ladar (SAIL) in which the target and carrying platform are kept still during the collection process is proposed and demonstrated. A target point of 0.5 mm \times 0.5 mm and a two-dimensional (2D) object are reconstructed in the experiments, in which an optical collimator with a focal length of 10 m is used to simulate the far-field condition. The achieved imaging resolution is in agreement with the theoretical design. The static-mode down-looking SAIL has the capability to eliminate the influence from the atmospheric turbulence and can be conveniently operated outdoors.