Dual-branch feature fusion S3D V-Net network for lung nodules segmentation.

BACKGROUND: Accurate segmentation of lung nodules can help doctors get more accurate results and protocols in early lung cancer diagnosis and treatment planning, so that patients can be better detected and treated at an early stage, and the mortality rate of lung cancer can be reduced. PURPOSE: Currently, the improvement of lung nodule segmentation accuracy has been limited by his heterogeneous performance in the lungs, the imbalance between segmentation targets and background pixels, and other factors. We propose a new 2.5D lung nodule segmentation network model for lung nodule segmentation. This network model can well improve the extraction of edge information of lung nodules, and fuses intra-slice and inter-slice features, which makes good use of the three-dimensional structural information of lung nodules and can more effectively improve the accuracy of lung nodule segmentation. METHODS: Our approach is based on a typical encoding-decoding network structure for improvement. The improved model captures the features of multiple nodules in both 3-D and 2-D CT images, complements the information of the segmentation target's features and enhances the texture features at the edges of the pulmonary nodules through the dual-branch feature fusion module (DFFM) and the reverse attention context module (RACM), and employs central pooling instead of the maximal pooling operation, which is used to preserve the features around the target and to eliminate the edge-irrelevant features, to further improve the performance of the segmentation of the pulmonary nodules. RESULTS: We evaluated this method on a wide range of 1186 nodules from the LUNA16 dataset, and averaging the results of ten cross-validated, the proposed method achieved the mean dice similarity coefficient (mDSC) of 84.57%, the mean overlapping error (mOE) of 18.73% and average processing of a case is about 2.07 s. Moreover, our results were compared with inter-radiologist agreement on the LUNA16 dataset, and the average difference was 0.74%. CONCLUSION: The experimental results show that our method improves the accuracy of pulmonary nodules segmentation and also takes less time than more 3-D segmentation methods in terms of time.

Exploring noncoding RNAs in thyroid cancer using a graph convolutional network approach.

Noncoding RNAs (ncRNAs) are crucial regulators in initiating and promoting thyroid cancer. Exploring the relationship between ncRNAs and thyroid cancer is essential for the diagnosis and treatment of thyroid cancer. Wet-lab experiments are costly and are difficult to conduct on a large scale. Although there are several ncRNA and cancer-related databases, there are few data related to thyroid cancer. There is a lack of computational approaches for predicting ncRNA-thyroid cancer associations. This work describes TCGCN, a linear residual graph convolution network to predict ncRNA-thyroid cancer associations. We collected a large amount of ncRNA-disease association data and constructed a bipartite graph. We use a simple linear embedding propagation at each convolutional layer and use the weighted sum of the embeddings on all graph convolutional layers to make the final prediction. In 5-fold cross-validation on the ncRNA-thyroid cancer dataset, TCGCN obtained significantly better performances with an AUC of 0.8162 and an AUPR of 0.8049, which are considerably better than those of other state-of-the-art approaches. We also demonstrate the usability of our method in the case studies.

Large investment of stored nitrogen and phosphorus in female cones is consistent with infrequent reproduction events of Pinus koraiensis, a high value woody oil crop in Northeast Asia.

Pinus koraiensis is famous for its high-quality timber production all the way and is much more famous for its high value health-care nut oil production potential since 1990's, but the less understanding of its reproduction biology seriously hindered its nut productivity increase. Exploring the effects of reproduction on nutrient uptake, allocation and storage help to understand and modify reproduction patterns in masting species and high nut yield cultivar selection and breeding. Here, we compared seasonality in growth and in nitrogen ([N]) and phosphorus ([P]) concentrations in needles, branches and cones of reproductive (cone-bearing) and vegetative branches (having no cones) of P. koraiensis during a masting year. The growth of one- and two-year-old reproductive branches was significantly higher than that of vegetative branches. Needle, phloem and xylem [N] and [P] were lower in reproductive branches than in vegetative branches, although the extent and significance of the differences between branch types varied across dates. [N] and [P] in most tissues were high in spring, decreased during summer, and then recovered by the end of the growing season. Overall, [N] and [P] were highest in needles, lowest in the xylem and intermediate in the phloem. More than half of the N (73.5%) and P (51.6%) content in reproductive branches were allocated to cones. There was a positive correlation between cone number and N and P content in needles (R2 = 0.64, R2 = 0.73) and twigs (R2 = 0.65, R2 = 0.62) of two-year-old reproductive branches. High nutrient sink strength of cones and vegetative tissues of reproductive branches suggested that customized fertilization practices can help improve crop yield in Pinus koraiensis.

Molecular Architecture of a Network of Potential Intracellular EGFR Modulators: ARNO, CaM, Phospholipids, and the Juxtamembrane Segment.

Epidermal growth factor receptors (EGFRs) are central cellular signaling interfaces whose misregulation is related to several severe diseases. Although ligand binding to the extracellular domain is the most obvious regulatory element, also intracellular factors can act as modulators of EGFR activity. The juxtamembrane (JM) segment seems to be the receptor's key interaction interface of these cytoplasmic factors. However, only a limited number of cytoplasmic EGFR modulators are known and a comprehensive understanding of their mode of action is lacking. Here, we report ARNO, a member of the cytohesin family, as another JM-binding protein and structurally characterize the ARNO-EGFR interaction interface. We reveal that its binding mode displays common features and distinct differences with JM's interaction with calmodulin and anionic phospholipids. Furthermore, we show that each interaction can be modulated by additional factors, generating a distinctly regulated network of possible EGFR modulators acting on the intracellular domain of the receptor.

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To explore the nutrient source and supply-demand relationship of the female cone deve-lopment and new shoot growth of Pinus koraiensis, reproductive mother branches were experimentally girdled, defoliated, and under the combination of both treatments. The effects of different treatments on the female cones development, branch growth and the content of carbohydrate (NSC), nitrogen (N) and phosphorus (P) in different tissues and organs were measured. The results showed that girdling significantly affected female cone development, new shoot growth, and the contents of NSC, N and P in different tissues and organs, while defoliation treatment had limited effect. The NSC content in the mother branch xylem and phloem after girdling were significantly lower than that of the control (CK, ungirdling+0% defoliation), and decreased significantly with the increases of the degree of defoliation. The NSC content in mother branch xylem and phloem of girdling+100% defoliation was 59.0% and 64.8% lower than that of CK, respectively. The deficiency of NSC resulted in the death of mother branches and new shoots and the abortion of female cone. Under girdling treatment, the contents of N and P in xylem and phloem of mother branches of 0%, 50% and 100% defoliation treatment were significantly higher than that of CK. The contents of N and P in xylem of mother branches were 17.3%, 18.2% and 24.3% and 17.9%, 7.1% and 3.6% higher than those of CK, respectively. The contents of N and P in phloem of mother branches was 39.3%, 35.2% and 48.9% and 31.0%, 28.2% and 14.8% higher than those of CK, respectively. The female cone development and new shoot growth of P. koraiensis consumed a large amount of NSC, N and P. The carbohydrates and mineral nutrients manufactured or stored in the mother branches could not meet the needs of female cone development and new shoot growth, and thus they need to be imported from other tissues.

Inhibitor-Directed Spin Labelling-A High Precision and Minimally Invasive Technique to Study the Conformation of Proteins in Solution.

Pulsed electron-electron double resonance spectroscopy (known as PELDOR or DEER) has recently become a very popular tool in structural biology. The technique can be used to accurately measure distance distributions within macromolecules or macromolecular complexes, and has become a standard method to validate structural models and to study the conformational flexibility of macromolecules. It can be applied in solution, in lipid environments or even in cells. Because most biological macromolecules are diamagnetic, they are normally invisible for PELDOR spectroscopy. To render a particular target molecule accessible for PELDOR, it can be engineered to contain only one or two surface-exposed cysteine residues, which can be efficiently spin-labelled using thiol-reactive nitroxide compounds. This method has been coined "site-directed spin labelling" (SDSL) and is normally straight-forward. But, SDSL can be very challenging for proteins with many native cysteines, or even a single functionally or structurally important cysteine residue. For such cases, alternative spin labelling techniques are needed. Here we describe the concept of "inhibitor-directed spin labelling" (IDSL) as an approach to spin label suitable cysteine-rich proteins in a site-directed and highly specific manner by employing bespoke spin-labelled inhibitors. Advantages and disadvantages of IDSL are discussed.

Studying the Conformation of a Receptor Tyrosine Kinase in Solution by Inhibitor-Based Spin Labeling.

The synthesis of a spin label based on PD168393, a covalent inhibitor of a major anticancer drug target, the epidermal growth factor receptor (EGFR), is reported. The label facilitates the analysis of the EGFR structure in solution by pulsed electron paramagnetic resonance (EPR) spectroscopy. For various EGFR constructs, including near-full-length EGFR, we determined defined distance distributions between the two spin labels bound to the ATP binding sites of the EGFR dimer. The distances are in excellent agreement with an asymmetric dimer of the EGFR. Based on crystal structures, this dimer had previously been proposed to reflect the active conformation of the receptor but structural data demonstrating its existence in solution have been lacking. More generally, our study provides proof-of-concept that inhibitor-based spin labeling enables the convenient introduction of site-specific spin labels into kinases for which covalent or tight-binding small-molecule modulators are available.

The interaction between viral protein and host actin facilitates the virus infection to host.

Although the virus-host interaction has attracted extensive studies, the host proteins essential for virus infection remain largely unknown. To address this issue, the shrimp Penaeus stylirostris densovirus (PstDNV), belonging to the family Parvoviridae, was characterized. PstDNV, a single-stranded DNA virus with a 3.9-kb genome, encoded only three open reading frames (ORFs). Among the three viral proteins, the PstDNV ORF2-encoded protein was discovered to interact with the shrimp actin, suggesting that the host actin played a very important role in virus infection. The RNAi assays revealed that the ORF2-encoded protein was required for the PstDNV infection. The confocal evidence demonstrated that the interaction between the ORF2-encoded protein and actin was essential for the virus infection. Therefore our study indicated that the manipulation of the host actin cytoskeleton was a necessary strategy for viral pathogens to invade host cells.