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Drawing upon the Taoist philosophies related to Yin and harmonious dialectics, this article intends to provide an innovative perspective on the interpretation of The Earthsea Cycle and feminism. Th...

The Brassicaceae is an important plant family. We built a user-friendly, web-based, comparative, and functional genomic database, The Brassicaceae Genome Resource (TBGR, http://www.tbgr.org.cn), based on 82 released genomes from 27 Brassicaceae species. The TBGR database contains a large number of important functional genes, including 4,096 glucosinolate genes, 6,625 auxin genes, 13,805 flowering genes, 36,632 resistance genes, 1,939 anthocyanin genes, and 1,231 m6A genes. A total of 1,174,049 specific guide sequences for clustered regularly interspaced short palindromic repeats and 5,856,479 transposable elements were detected in Brassicaceae. TBGR also provides information on synteny, duplication, and orthologs for 27 Brassicaceae species. The TBGR database contains 1,183,851 gene annotations obtained using the TrEMBL, Swiss-Prot, Nr, GO, and Pfam databases. The BLAST, Synteny, Primer Design, Seq_fetch, and JBrowse tools are provided to help users perform comparative genomic analyses. All the genome assemblies, gene models, annotations, and bioinformatics results can be easily downloaded from the TBGR database. We plan to improve and continuously update the database with newly assembled genomes and comparative genomic studies. We expect the TBGR database to become a key resource for the study of the Brassicaceae.

The purpose of this study was to compare the diagnostic performance of ultrasonography (US) and mammography in the differential diagnosis of breast lesions after adding different types of elastography to US.This institutional review board-approved study included 316 breast lesions in 289 women between July 2016 and July 2018. All these lesions were evaluated with conventional US, elastography, and mammography before biopsy or surgery. Elastography, including elasticity imaging (EI), virtual touch tissue imaging (VTI), and virtual touch imaging quantification (VTIQ), were used to downgrade US Breast Imaging-Reporting and Data System category 4A lesions. Diagnostic performances were calculated for mammography, US elastography, and the combination of US and elastography.The sensitivity of US (100%) was significantly higher than that of mammography (84.6%; P .001), but the specificity of US (14.5%) was significantly lower than that of mammography (59.1%; P .001). After adding EI, VTI, and VTIQ to US, the specificity was significantly increased from 14.5% to 69.4%, 72.6%, and 78.0%, respectively (P .001), and were significantly higher than that of mammography (P = .043, P = .006, and P .001, respectively). The sensitivity of US + EI (96.2%) and US + VTI (96.2%) was lower than that of US alone, although not significantly (100%; P = .063 and P = .063, respectively).The addition of different types of elastography to US improved the diagnostic performance in the differential diagnosis of breast lesions when compared with mammography.

The aim of our study was to compare strain elastography (SE), acoustic radiation force impulse-inducing Virtual Touch Imaging ([VTI] Siemens Medical Solutions, Mountain View, CA, USA), Virtual Touch Imaging Quantification ([VTIQ] Siemens Medical Solutions) and combined methods in the evaluation of ultrasound (US) Breast Imaging-Reporting and Data System (BI-RADS) category 4 lesions to explore an applicable way to reduce unnecessary biopsy by reducing false positives of conventional US without yielding false-negative cases. A total of 267 patients with 278 BI-RADS category 4 lesions (151 benign and 127 malignant) were evaluated with conventional B-mode US, SE, VTI and VTIQ implemented on a Siemens Acuson S2000 US system. Diagnostic performance, including area under the receiver operating characteristic curve, sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were evaluated. Overall, VTI alone exhibited the highest NPV (91.74%), although combined elastic methods exhibited higher NPV than single methods, with the highest NPV at 100% when the VTI, SE and VTIQ methods were combined. Compared with conventional US, PPV increased from 45.7% (127 of 278) to 63.18% (127 of 201) when adding combined elastography (VTI + SE +VTIQ). In addition, 52.5% (63/120) and 50.8% (61/120) of BI-RADS 4 A lesions were downgraded when using combined methods (VTI + SE and VTI + SE + VTIQ, respectively) without missing any cancer. However, 2 intraductal papillomas and 1 phyllodes tumor were not identified. In conclusion, the combination of different elastic methods have the potential to downgrade BI-RADS 4A lesions to reduce false-positive biopsies without increasing the risk of missing cancers.

Objective: To evaluate the correlation between elastic heterogeneity (EH) and lymphovascular invasion (LVI) in breast cancers and assess the clinical value of using EH to predict LVI pre-operatively. Methods: This retrospective study consisted of 376 patients with breast cancers that had undergone shear wave elastography (SWE) with virtual touch tissue imaging quantification between June 2017 and June 2018. The EH was determined as the difference between the averaged three highest and three lowest shear wave value. Clinicalpathological parameters including histological type and grades, LVI, axillary lymph node status and molecular markers (estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 and Ki-67) were reviewed and recorded. Relationship EH and clinicalpathological parameters was investigated respectively. The diagnostic performance of EH in distinguishing LVI or not was analyzed. Results: At multivariate regression analysis, only EH (p = 0.017) was positively correlated with LVI in all tumors. EH (p = 0.003) and Ki-67 (p = 0.025) were positively correlated with LVI in tumors ≤ 2 cm. None of clinicalpathological parameters were correlated with LVI in tumors > 2 cm (p > 0.05 for all). Using EH to predict LVI in tumors ≤ 2 cm, the sensitivity and negative predictive value were 93 and 89% respectively. Conclusion: EH has the potential to be served as an imaging biomarker to predict LVI in breast cancer especially for tumors ≤ 2 cm. Advances in knowledge: There was no association between LVI and other most commonly used elastic features such as SWVmean and SWVmax. Elastic heterogeneity is an independent predictor of LVI, so it can provide additional prognostic information for routine preoperative breast cancer assessment. For tumors ≤ 2cm, using EH value higher than 1.36 m/s to predict LVI involvement, the sensitivity and negative predictive value can reach to 93% and 89%, respectively, suggesting that breast cancer with negative EH value was more likely to be absent of LVI.

Accurate identification of axillary lymph node (ALN) involvement in patients with early-stage breast cancer is important for determining appropriate axillary treatment options and therefore avoiding unnecessary axillary surgery and complications. Here, we report deep learning radiomics (DLR) of conventional ultrasound and shear wave elastography of breast cancer for predicting ALN status preoperatively in patients with early-stage breast cancer. Clinical parameter combined DLR yields the best diagnostic performance in predicting ALN status between disease-free axilla and any axillary metastasis with areas under the receiver operating characteristic curve (AUC) of 0.902 (95% confidence interval [CI]: 0.843, 0.961) in the test cohort. This clinical parameter combined DLR can also discriminate between low and heavy metastatic burden of axillary disease with AUC of 0.905 (95% CI: 0.814, 0.996) in the test cohort. Our study offers a noninvasive imaging biomarker to predict the metastatic extent of ALN for patients with early-stage breast cancer.

To assess the diagnostic performance of the LR-M criteria of Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System version 2017 in differentiating intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC) in patients with and without risk factors for HCC. Fifty-four ICC in patients with risks and 55 ICC in patients without risks and matched control cases of HCC with and without risks (n = 59 and n = 55, respectively) were enrolled. The enhanced features of the lesions were retrospectively analyzed according to LR-M criteria. The diagnostic performances including the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of LR-M criteria were assessed. Peripheral rim-like hyperenhancement, early washout (

The Legionella pneumophila effector MavC is a transglutaminase that carries out atypical ubiquitination of the host ubiquitin (Ub)‐conjugation enzyme UBE2N by catalyzing the formation of an isopeptide bond between Gln40Ub and Lys92UBE2N, which leads to inhibition of signaling in the NF‐κB pathway. In the absence of UBE2N, MavC deamidates Ub at Gln40 or catalyzes self‐ubiquitination. However, the mechanisms underlying these enzymatic activities of MavC are poorly understood at the molecular level. This study reports the structure of the MavC–UBE2N–Ub ternary complex representing a snapshot of MavC‐catalyzed crosslinking of UBE2N and Ub, which reveals the way by which UBE2N–Ub binds to the Insertion and Tail domains of MavC. Based on the structural and experimental data, the catalytic mechanism for the deamidase and transglutaminase activities of MavC is proposed. Finally, by comparing the structures of MavC and MvcA, the homologous protein that reverses MavC‐induced UBE2N ubiquitination, several essential regions and two key residues (Trp255MavC and Phe268MvcA) responsible for their respective enzymatic activities are identified. The results provide insights into the mechanisms for substrate recognition and ubiquitination mediated by MavC as well as explanations for the opposite activity of MavC and MvcA in terms of regulation of UBE2N ubiquitination., The pathogen Legionella pneumophila evades immune detection by deploying the transglutaminase effector MavC to ubiquitinate the host ubiquitin‐conjugating enzyme UBE2N. This work presents the structure of MavC–UBE2N–Ub ternary complex and sheds light on the molecular basis for MavC‐induced transglutamination and its mechanistic differences with its homolog MvcA, which counteracts MavC activity by deubiquitinating modified UBE2N in later phases of infection.

The Legionella pneumophila effector MavC induces ubiquitination of the E2 ubiquitin‐conjugating enzyme UBE2N by transglutamination, thereby abolishing its function in the synthesis of K(63)‐type polyubiquitin chains. The inhibition of UBE2N activity creates a conundrum because this E2 enzyme is important in multiple signaling pathways, including some that are important for intracellular L. pneumophila replication. Here, we show that prolonged inhibition of UBE2N activity by MavC restricts intracellular bacterial replication and that the activity of UBE2N is restored by MvcA, an ortholog of MavC (50% identity) with ubiquitin deamidase activity. MvcA functions to deubiquitinate UBE2N‐Ub using the same catalytic triad required for its deamidase activity. Structural analysis of the MvcA‐UBE2N‐Ub complex reveals a crucial role of the insertion domain in MvcA in substrate recognition. Our study establishes a deubiquitination mechanism catalyzed by a deamidase, which, together with MavC, imposes temporal regulation of the activity of UBE2N during L. pneumophila infection.

Proteasomes are highly abundant and conserved protease complexes that eliminate unwanted proteins in the cells. As a single-chain ATP-independent nuclear proteasome activator, proteasome activator 200 (PA200) associates with 20S core particle to form proteasome complex that catalyzes polyubiquitin-independent degradation of acetylated histones, thus playing a pivotal role in DNA repair and spermatogenesis. Here, we present cryo–electron microscopy (cryo-EM) structures of the human PA200-20S complex and PA200 at 2.72 Å and 3.75 Å, respectively. PA200 exhibits a dome-like architecture that caps 20S and uses its C-terminal YYA (Tyr-Tyr-Ala) to induce the α-ring rearrangements and partial opening of the 20S gate. Our structural data also indicate that PA200 has two openings formed by numerous positively charged residues that respectively bind (5,6)-bisdiphosphoinositol tetrakisphosphate (5,6[PP]2-InsP4) and inositol hexakisphosphate (InsP6) and are likely to be the gates that lead unfolded proteins through PA200 and into the 20S. Besides, our structural analysis of PA200 found that the bromodomain (BRD)-like (BRDL) domain of PA200 shows considerable sequence variation in comparison to other human BRDs, as it contains only 82 residues because of a short ZA loop, and cannot be classified into any of the eight typical human BRD families. Taken together, the results obtained from this study provide important insights into human PA200-induced 20S gate opening for substrate degradation and the opportunities to explore the mechanism for its recognition of H4 histone in acetylation-mediated proteasomal degradation., Proteasomes are highly abundant and conserved protease complexes that eliminate unwanted proteins in the cells. The cryo-EM structures of PA200 and the PA200-20S proteasome complex reveal two openings on PA200 which bind inositol phosphates as cofactors, and novel insights into PA200-induced gate-opening of 20S.

OBJECTIVES To evaluate the association between shear wave elastography parameters using virtual touch tissue imaging quantification (VTIQ) and the Ki-67 index in luminal-type breast cancer. METHODS Eighty-one patients with 82 lesions of pathologic confirmed luminal-type breast cancer underwent virtual touch tissue imaging quantification examination before surgery between December 2015 and June 2016. Patients were divided into 2 groups according to the Ki-67 index (≥14% versus

The Earthsea Cycle by Ursula K. Le Guin, regarded as one of the most successful Western fantasy novels worldwide, constructs for the readers a fantasy Earthsea world where the harmonious combination of Oriental philosophy and Western literature lays the pillar. Drawing upon the philosophy of Taoism and Tao Te Ching, and resorting to the analysis of the three most significant elements in the book, true name, this essay conducts a profound and comprehensive exploration of the Taoist wonders in The Earthsea Cycle. This essay illustrates the connections among true name, language creation view and Tao to reveal how true name reflects the nature of life and existence. At last, the essay concludes that The Earthsea Cycle is a literary work of Western fantasy entwined with Oriental Taoist philosophy. True name is the essence of existence in the Earthsea world, while magic originates from the need to develop while following the course of nature. All things in The Earthsea Cycle rely on nature and inaction, and grow within the circle of life.

Background This study was aimed to assess whether ultrasonic spectrum analysis of radiofrequency (RF) time series using a clinical ultrasound system allows for early differentiating between the chemotherapy responders and nonresponders in human breast cancer xenografts that imitate clinical responding and nonresponding tumors. Methods Clinically responding (n = 20; MCF-7) and nonresponding (n = 20; MBA-MD-231) breast cancer xenografts were established in 40 nude mice. Ten mice from each group received either chemotherapy (adriamycin, 4 mg/kg) or saline as controls. Each tumor was imaged longitudinally with a clinical ultrasound scanner at baseline (day 0) and subsequently on days 2, 4, 6, 8 and 12 following treatment, and the corresponding RF time-series data were collected. Changes in six RF time-series parameters (slope, intercept, S1, S2, S3 and S4) were compared with the measurement of the tumor cell density, and their differential performances of the treatment response were analyzed. Results Adriamycin significantly inhibited tumor growth and decreased the cancer cell density in responders (P 0.05). Fold changes of slope were significantly increased in responders two days after adriamycin treatment (P = 0.002), but not in nonresponders (P > 0.05). Early changes in slope on day 2 could differentiate the treatment response in 100% of both responders (95% CI, 62.9–100.0%) and nonresponders (95% CI, 88.4–100%). Conclusions Ultrasonic RF time series allowed for the monitoring of the tumor response to chemotherapy and could further serve as biomarkers for early differentiating between the treatment responders and nonresponders. Electronic supplementary material The online version of this article (10.1186/s40644-019-0248-y) contains supplementary material, which is available to authorized users.

OBJECTIVE To determine the added value of a shear-wave elastography (SWE) quality map (QM) in the diagnosis of breast lesions and in predicting the biological characteristics of invasive breast cancer. MATERIALS AND METHODS Between January 2016 and February 2019, this study included 368 women with 368 pathologically proven breast lesions, which appeared as poor-quality regions in the QM of SWE. To measure shear-wave velocity (SWV), seven regions of interest were placed in each lesion with and without QM guidance. Under QM guidance, poor-quality areas were avoided. Diagnostic performance was calculated for mean SWV (SWVmean), max SWV (SWVmax), and standard deviation (SD) with QM guidance (SWVmean + QM, SWVmax + QM, and SD + QM, respectively) and without QM guidance (SWVmean - QM, SWVmax - QM, and SD - QM, respectively). For invasive cancers, the relationship between SWV findings and biological characteristics was investigated with and without QM guidance. RESULTS Of the 368 women (mean age, 47 years; SD, 10.8 years) enrolled, 159 had benign breast lesions and 209 had malignant breast lesions. SWVmean + QM (3.6 ± 1.39 m/s) and SD + QM (1.02 ± 0.84) were significantly different from SWVmean - QM (3.29 ± 1.22 m/s) and SD - QM (1.46 ± 1.06), respectively (all p < 0.001). For differential diagnosis of breast lesions, the sensitivity and areas under the receiver operating characteristic curve (AUC) of SWVmean + QM (sensitivity: 89%; AUC: 0.932) were better than those of SWVmean - QM (sensitivity, 84.2%; AUC, 0.912) (all p < 0.05). There was no significant difference in sensitivity and specificity between SD + QM and SD - QM (all p = 1.000). Among the biological characteristics of invasive cancers, lymphovascular involvement, axillary lymph node metastasis, negative estrogen receptor status, negative progesterone receptor status, positive human epidermal growth factor receptor status, and aggressive molecular subtypes showed higher SWVmean + QM (all p < 0.05), while only lymphovascular involvement showed higher SWVmean - QM (p = 0.036). CONCLUSION The use of QM in SWE might improve the diagnostic performance for breast lesions and facilitate prediction of the biological characteristics of invasive breast cancers.

To assess the diagnostic performance of the LR-M criteria of Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System version 2017 in differentiating intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC) in patients with and without risk factors for HCC.Fifty-four ICC in patients with risks and 55 ICC in patients without risks and matched control cases of HCC with and without risks (n = 59 and n = 55, respectively) were enrolled. The enhanced features of the lesions were retrospectively analyzed according to LR-M criteria. The diagnostic performances including the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of LR-M criteria were assessed.Peripheral rim-like hyperenhancement, early washout ( 45 or 60s), and marked washout did not differ between ICCs with and without risks, while all of these features were more common in ICCs than in HCCs (p 0.05) no matter if patients were with and without risk factors. Using the LR-M criteria to differentiate ICC from HCC, the AUC, sensitivity, specificity, and accuracy were 0.92, 97.25%, 87.72%, and 92.38%, respectively. If early washout onset was adjusted to 45 s, the specificity was significantly increased to 95.61% (p = 0.004) without losing sensitivity (96.33%, p = 0.945). The rate of HCCs misdiagnosed as ICCs would decrease from 12.3 to 4.4%.Although the LR-M criteria showed high sensitivity in distinguishing ICCs from HCCs in patients with and without risks, the specificity would be significantly increased after adjustments to current criteria.• The LR-M criteria of CEUS-LI-RADS v2017 could be used for distinguishing ICC from HCC not only in patients with risk factors for HCC but also in those without risk factors. • The diagnostic performance of differentiating ICC from HCC by using the LR-M criteria showed high AUC (0.92), high sensitivity (97.25%), intermediate specificity (87.72%), and high accuracy (92.38%). • If the onset of early washout was adjusted to 45 s, the specificity was significantly increased from 87.72 to 95.61% (p = 0.004) without losing sensitivity (p = 0.945), and the rate of HCCs misdiagnosed as ICCs would decrease from 12.3 to 4.4%.

The aim of this study was to evaluate whether quantitative analysis of elastic heterogeneity (EH) could improve the diagnostic performance of shear wave elastography (SWE) in breast lesions. From August 2016 to August 2017, 280 patients were enrolled in this prospective study. All lesions were evaluated with the ultrasound Breast Imaging Reporting and Data System (BI-RADS) and SWE with Virtual Touch tissue imaging quantification. The shear wave velocity (SWV) of the three areas of highest stiffness and lowest stiffness within the lesions were measured to calculate the maximum SWV (SWVmax), mean SWV (SWVmean) and EH. The EH was determined as the difference between the averaged highest SWV and lowest SWV. The diagnostic performance-including the area under the receiver operating characteristic curve (AUC) and the sensitivity and specificity of BI-RADS, EH, SWVmax and SWVmean-were analyzed. The AUC of EH, SWVmax and SWVmean were 0.963, 0.949 and 0.937, respectively. The sensitivity of EH was 93.75%, which was significantly higher than that of SWVmax (84.37%) and SWVmean (84.37%) (p 0.05). For category 4A lesions, EH predicted all the malignant lesions, while two cancers were misdiagnosed by SWVmax and SWVmean, respectively. Quantitative analysis of EH can improve the sensitivity of SWE for the differential diagnosis of breast lesions without loss of specificity.

Detailed process of RF time series data analysis. (DOCX 32 kb)

To determine whether a combination of different types of elastography could improve the accuracy of elastography-aided downgrading ultrasound (US) Breast Imaging-Reporting and Data System (BI-RADS) category 4a lesions. From January 2016 to May 2018, 458 consecutive women with 494 US BI-RADS category 4a breast lesions were enrolled in the prospective study. These lesions were subject to conventional US supplemented with strain elastography of elasticity imaging (EI), virtual touch tissue imaging (VTI), and shear wave elastography of virtual touch imaging quantification (VTIQ). Diagnostic performances were calculated for BI-RADS, EI, VTI, and VTIQ as well as the combination of EI, VTI, and VTIQ (combination of EI and VTI [EI + VTI], combination of EI and VTIQ [EI + VTIQ], and combination of VTI and VTIQ [VTI + VTIQ]). Pathologically, 445 lesions (90.1%) were benign, and 49 (9.9%) were malignant. The specificities of EI, VTI, and VTIQ were significantly higher than those of BI-RADS (69.9%, 83.8%, 75.5% vs. 0, respectively, P

Purpose To determine the diagnostic performance of ultrasonography (US) and mammography in the differential diagnosis of breast lesions after adding different types of elastography to US. Materials and Methods This institutional review board-approved study included 316 US detected masses in 280 women between January 2016 and July 2018. All these lesions were evaluated with conventional ultrasonography, elastography and mammography prior to biopsy or surgery. Each lesion was underwent evaluated with three type of elastography including elasticity imaging (EI), virtual touch tissue imaging (VTI) and Virtual Touch Imaging Quantification (VTIQ). US breast Imaging-Reporting and Data System (BI-RADS) category 4A lesions would be downgraded if on positive findings on elastography. Diagnostic performances were calculated for mammography, US elastography and the combination of US and elastography. Results Of 316 breast lesions, 134 were malignant. The sensitivity of conventional US (100%) was significantly higher than that of mammography (84.6%, p Conclusion The combinations of US and EI, VTI improved the specificity without sacrificing sensitivity which showed a better diagnostic performance in the differential diagnosis of breast lesions than mammography