Deep Learning Combined with Radiologist's Intervention Achieves Accurate Segmentation of Hepatocellular Carcinoma in Dual-Phase Magnetic Resonance Images.

Purpose: Segmentation of hepatocellular carcinoma (HCC) is crucial; however, manual segmentation is subjective and time-consuming. Accurate and automatic lesion contouring for HCC is desirable in clinical practice. In response to this need, our study introduced a segmentation approach for HCC combining deep convolutional neural networks (DCNNs) and radiologist intervention in magnetic resonance imaging (MRI). We sought to design a segmentation method with a deep learning method that automatically segments using manual location information for moderately experienced radiologists. In addition, we verified the viability of this method to assist radiologists in accurate and fast lesion segmentation. Method: In our study, we developed a semiautomatic approach for segmenting HCC using DCNN in conjunction with radiologist intervention in dual-phase gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid- (Gd-EOB-DTPA-) enhanced MRI. We developed a DCNN and deep fusion network (DFN) trained on full-size images, namely, DCNN-F and DFN-F. Furthermore, DFN was applied to the image blocks containing tumor lesions that were roughly contoured by a radiologist with 10 years of experience in abdominal MRI, and this method was named DFN-R. Another radiologist with five years of experience (moderate experience) performed tumor lesion contouring for comparison with our proposed methods. The ground truth image was contoured by an experienced radiologist and reviewed by an independent experienced radiologist. Results: The mean DSC of DCNN-F, DFN-F, and DFN-R was 0.69 ± 0.20 (median, 0.72), 0.74 ± 0.21 (median, 0.77), and 0.83 ± 0.13 (median, 0.88), respectively. The mean DSC of the segmentation by the radiologist with moderate experience was 0.79 ± 0.11 (median, 0.83), which was lower than the performance of DFN-R. Conclusions: Deep learning using dual-phase MRI shows great potential for HCC lesion segmentation. The radiologist-aided semiautomated method (DFN-R) achieved improved performance compared to manual contouring by the radiologist with moderate experience, although the difference was not statistically significant.

Roles of trained immunity in the pathogenesis of periodontitis.

Periodontitis is a chronic, inflammatory, and destructive disease caused by the imbalance of host immune response and dental biofilm, and has strong epidemiological and pathogenesis correlations with systemic diseases. The immune response in periodontitis involves both innate and adaptive immunity, with numerous immune cells and inflammatory pathways participating in a complex network of interactions. In the past decade, the concept of "trained immunity" has emerged, which highlights the memory characteristics of innate immunity, thus opening up a new avenue of research. There is growing interest in exploring the role of trained immunity in chronic inflammatory and metabolic diseases such as atherosclerosis and diabetes mellitus. Evidence suggests that trained immunity may also regulate the onset and progression of periodontitis, serving as a bridge between periodontitis-related comorbidities. In this review, we summarize concepts related to trained immunity and its development. Furthermore, we present current evidence that endorses the notion of trained immunity in periodontitis and analyze possible roles it may assume regarding periodontitis-associated inflammatory reactions from a cellular perspective. Finally, we discuss various clinical therapeutic strategies for periodontitis and its associated comorbidities that target trained immunity. We hope that more researchers will pay attention to this emerging concept, thereby providing deeper insights into this novel field.

Piezo1-mediated M2 macrophage mechanotransduction enhances bone formation through secretion and activation of transforming growth factor-ß1.

Macrophages are multifunctional immune system cells that are essential for the mechanical stimulation-induced control of metabolism. Piezo1 is a non-selective calcium channel expressed in multifarious tissues to convey mechanical signals. Here, a cellular model of tension was used to study the effect of mechanical stretch on the phenotypic transformation of macrophages and its mechanism. An indirect co-culture system was used to explore the effect of macrophage activation on bone marrow mesenchymal stem cells (BMSCs), and a treadmill running model was used to validate the mechanism in vivo for in vitro studies. p53 was acetylated and deacetylated by macrophages as a result of mechanical strain being detected by Piezo1. This process is able to polarize macrophages towards M2 and secretes transforming growth factor-beta (TGF-ß1), which subsequently stimulates BMSCs migration, proliferation and osteogenic differentiation. Knockdown of Piezo1 inhibits the conversion of macrophages to the reparative phenotype, thereby affecting bone remodelling. Blockade of TGF-ß I, II receptors and Piezo1 significantly reduced exercise-increased bone mass in mice. In conclusion, we showed that mechanical tension causes calcium influx, p53 deacetylation, macrophage polarization towards M2 and TGF-ß1 release through Piezo1. These events support BMSC osteogenesis.

Bone-targeted bortezomib increases bone formation within Calvarial trans-sutural distraction osteogenesis.

The high rate of relapse in craniofacial disharmony treatment via trans-sutural distraction osteogenesis (TSDO) is due to the failure to form a stable bone bridge in the suture gap. Bisphosphonates (BP) have a high propensity to localize to hydroxyapatite in the bone matrix and are commonly used as targeting ligands for local delivery of therapeutics into bone microenvironment. Bone-targeted Bortezomib (BP-Btz) is chemosynthetic by linking Btz (Bortezomib) to a BP residue and could target bone tissue to promote osteoblast differentiation and inhibit osteoclastogenesis. Here, suture-derived mesenchymal stem cells (SuSCs) and osteoclasts were treated with Btz and BP-Btz. Aforesaid drugs were injected locally into the sagittal sutures to explore their effects in TSDO. Further, pharmacological properties of BP-Btz in the suture expansion model were assessed by fluorescent BP analogs and levels of total ubiquitinated (Ub)-proteins. The results showed that BP-Btz could stimulate osteogenic differentiation of SuSCs, bind to bone matrix and inhibit osteoclastogenesis. Biological effects of BP-Btz were similar with those of Btz in osteoblast differentiation and osteoclastogenesis inhibition in vitro. Activated bone metabolism were detected after 14 days in the sagittal suture expansion model. Increased osteoid area, remarkably decreased osteoclast surface and enhanced osteogenesis were detected in vivo after treatment with BP-Btz. Green fluorescence signal detection and pharmacodynamic studies revealed that BP-Btz bound to suture edge, released Btz in remodeling conditions, had a higher local concentration and sustained longer than free Btz. This study delineated the clinical potential of bone-targeted Btz conjugate as an efficacious strategy to promote trans-sutural distraction osteogenesis.

Exploring Female EFL Teachers' Professional Agency for Their Sustainable Career Development in China: A Self-Discrepancy Theory Perspective.

A large and growing body of literature has investigated the role of teachers' agency in their career trajectories. However, far too little attention has been paid to English as a Foreign Language (EFL) teachers', especially female EFL teachers', professional agency for their career development in the Chinese higher education setting. To address this gap, this study explores female EFL teachers' professional agency from a self-discrepancy theory perspective, namely, how the participating teachers have perceived discrepancies in their professional development and how they have enacted their professional agency to realize sustainable development. Based on a metaphor investigation of 167 teachers and interviews with nine of them, the current study found that (1) there are certain discrepancies between female EFL teachers' self-guides and actual selves concerning their professional identity construction; (2) female EFL teachers' professional agency is manifested in the continuum of iteration, practical evaluation, and projectivity processes, as well as in the entity of personal and environmental factors; and 3) female EFL teachers' professional agency and gender identity are closely intertwined with each other. This study can offer implications for teacher agency research and female teachers' sustainable development at large.

Voxel-based morphometry analysis and machine learning based classification in pediatric mesial temporal lobe epilepsy with hippocampal sclerosis.

Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is a common type of pediatric epilepsy. We sought to evaluate whether the combination of voxel-based morphometry (VBM) and support vector machine (SVM), a machine learning method, was feasible for the classification of MTLE-HS. Three-dimensional T1-weighted MRI was acquired in 37 participants including 22 with MTLE-HS (16 left, 6 right) and 15 healthy controls (HCs). VBM was used to detect the regions of gray matter volume (GMV) abnormalities. The volumes of these regions were then calculated for each participant and used as the features in SVM. The SVM model was trained and tested with leave-one-out cross validation (LOOCV). We performed VBM-based comparison and SVM-based classification between left HS (LHS) and HC as well as between right HS (RHS) and HC. Both GMV increase and reduction were found in the group comparisons with VBM. Using SVM, we reached an area under the receiver operating characteristic curve (AUC) of 0.870, 0.976 and 0.902 for the classification between LHS and HC, between RHS and HC and between HS and HC respectively. The VBM findings were concordant with the clinical findings. Thus, our proposed method combining VBM findings with SVM, were applicable in the classification of padiatric MTLE-HS with high accuracy.

Transcriptome and expression profile analysis of highly resistant and susceptible banana roots challenged with Fusarium oxysporum f. sp. cubense tropical race 4.

Banana wilt disease, caused by the fungal pathogen Fusarium oxysporum f. sp. cubense 4 (Foc4), is regarded as one of the most devastating diseases worldwide. Cavendish cultivar 'Yueyoukang 1' was shown to have significantly lower disease severity and incidence compared with susceptible cultivar 'Brazilian' in greenhouse and field trials. De novo sequencing technology was previously performed to investigate defense mechanism in middle resistant 'Nongke No 1' banana, but not in highly resistant cultivar 'Yueyoukang 1'. To gain more insights into the resistance mechanism in banana against Foc4, Illumina Solexa sequencing technology was utilized to perform transcriptome sequencing of 'Yueyoukang 1' and 'Brazilian' and characterize gene expression profile changes in the both two cultivars at days 0.5, 1, 3, 5 and 10 after infection with Foc4. The results showed that more massive transcriptional reprogramming occurs due to Foc4 treatment in 'Yueyoukang 1' than 'Brazilian', especially at the first three time points, which suggested that 'Yueyoukang 1' had much faster defense response against Foc4 infection than 'Brazilian'. Expression patterns of genes involved in 'Plant-pathogen interaction' and 'Plant hormone signal transduction' pathways were analyzed and compared between the two cultivars. Defense genes associated with CEBiP, BAK1, NB-LRR proteins, PR proteins, transcription factor and cell wall lignification were expressed stronger in 'Yueyoukang 1' than 'Brazilian', indicating that these genes play important roles in banana against Foc4 infection. However, genes related to hypersensitive reaction (HR) and senescence were up-regulated in 'Brazilian' but down-regulated in 'Yueyoukang 1', which suggested that HR and senescence may contribute to Foc4 infection. In addition, the resistance mechanism in highly resistant 'Yueyoukang 1' was found to differ from that in middle resistant 'Nongke No 1' banana. These results explain the resistance in the highly resistant cultivar and provide more insights in understanding the compatible and incompatible interactions between banana and Foc4.

Proteomic analysis of Fusarium oxysporum f. sp. cubense tropical race 4-inoculated response to Fusarium wilts in the banana root cells.

BACKGROUND: Fusarium wilt of banana is one of the most destructive diseases in the world. This disease has caused heavy losses in major banana production areas. Except for molecular breeding methods based on plant defense mechanisms, effective methods to control the disease are still lacking. Dynamic changes in defense mechanisms between susceptible, moderately resistant, and highly resistant banana and Fusarium oxysporum f. sp. cubense tropical race 4 (Foc4) at the protein level remain unknown. This research reports the proteomic profile of three banana cultivars in response to Foc4 and transcriptional levels correlated with their sequences for the design of disease control strategies by molecular breeding. RESULTS: Thirty-eight differentially expressed proteins were identified to function in cell metabolism. Most of these proteins were positively regulated after Foc4 inoculation. These differentially regulated proteins were found to have important functions in banana defense response. Functional categories implicated that these proteins were associated with pathogenesis-related (PR) response; isoflavonoid, flavonoid, and anthocyanin syntheses; cell wall strengthening; cell polarization; reactive oxygen species production and scavenging; jasmonic acid-, abscisic acid-, and auxin-mediated signaling conduction; molecular chaperones; energy; and primary metabolism. By comparing the protein profiles of resistant and susceptible banana cultivars, many proteins showed obvious distinction in their defense mechanism functions. PR proteins in susceptible 'Brazil' were mainly involved in defense. The proteins related to PR response, cell wall strengthening and antifungal compound synthesis in moderately resistant 'Nongke No.1' were mainly involved in defense. The proteins related to PR response, cell wall strengthening, and antifungal compound synthesis in highly resistant 'Yueyoukang I' were mainly involved in defense. 12 differentially regulated genes were selected to validate through quantitative real time PCR method. Quantitative RT-PCR analyses of these selected genes corroborate with their respective protein abundance after pathogen infection. CONCLUSIONS: This report is the first to use proteomic profiling to study the molecular mechanism of banana roots infected with Foc4. The differentially regulated proteins involved in different defense pathways are likely associated with different resistant levels of the three banana cultivars.

RNA silencing suppressor Pns11 of rice gall dwarf virus induces virus-like symptoms in transgenic rice.

Transgenic rice (Oryza sativa) plants expressing the Pns11 protein of rice gall dwarf virus (RGDV) displayed multiple abnormal phenotypes, some of which were highly reminiscent of the symptoms observed in RGDV-infected rice. Further analysis indicated that the apparent alterations in plant growth and morphology were correlated with the expression levels of microRNA160, microRNA162, microRNA167, microRNA168, and the microRNA target OsARF8. Especially, the striking dwarfing phenotype depended on the high expression level of microRNA167. By analogy to other categories of plant viruses, the RNA silencing suppressors encoded by plant dsRNA viruses function as pathogenicity determinants. These findings significantly deepen our current mechanistic understanding of the RNA silencing suppressor (VSR) encoded by a dsRNA virus and provide additional evidence that interference with microRNA expression is a VSR function utilized by a diverse range of viruses.

[Main bacterial groups in banana soil under rotated and continuous cropping].

Banana wilt is the main disease in banana production, while banana-leek rotation can effectively control the occurrence of the disease. In order to understand the variations of soil bacterial groups under banana-leek rotation and banana continuous cropping, soil samples under these two cropping systems were collected to extract crude DNA, and the bacterial 16S rDNA in V3 region was amplified by PCR. The PCR products were then separated by DGGE, and the main different bands were sequenced and compared with the records of NCBI to identify the germs. Under banana-leek rotation, soil bacterial diversity was richer, and the main bacterial groups were Bacteroidetes, Proteobacteria, Actinobacteria, Chloroflexi, and Acidobacteria; while under banana continuous cropping, the soil bacterial diversity was somewhat decreased, and the main bacterial groups were Firmicutes, Proteobacteria, Actinobacteria, and Chloroflexi.

[Transgenic tobacco plants with ribosome inactivating protein gene cassin from Cassia occidentalis and their resistance to tobacco mosaic virus].

Cassin, the new gene of ribosome-inactivating protein (RIP) isolated from Cassia occidentalis, was inserted into expression vector pBI121 to produce plant expression vector pBI121-cassin (Figs.1, 2). pBI121-cassin was introduced into tobacco cultivar 'K326' by the Agrobacteriurm tumefaciens transformation method and more than 100 independent transformants were obtained. Southern blot hybridization analysis showed that a single gene locus was inserted into the chromosome of the transgenic tobacco lines (Fig.5) and PCR analysis of segregation population of progeny indicated that the inheritance of transgene was dominant in transgenic lines (Fig.4, Table 1). Results of RT-PCR and Northern blot hybridization analysis showed that transgene could be transcribed correctly (Figs.5, 6) . Three self-pollination lines of transgenic T(1) and T(2) were challenged with TMV at different concentration titers by mechanical inoculation. The transgenic lines exhibited different levels of resistance to TMV with the nontransgenic plants. After both titers of TMV concentration were inoculated, transgenic lines were considered as the highly resistant type with a delay of 4-13 d in development of symptoms and 10%-25% of test plants were infected, while nontransgenic control plants were susceptible typical symptoms on the newly emerged leaves (Table 2). One T(2) line, T(2)-8-2-1, was regarded as an immune type because it did not show any symptoms during 70 d and all plants were shown to be virus free by ELISA tests.