Compound shougong powder inhibits the malignant phenotype of hepatocellular carcinoma cells by targeting the DNA damage repair pathway.

OBJECTIVES: Compound Shougong Powder (SGS), a traditional Chinese medicine formulation, has been used to treat cancer for many years with remarkable efficacy. However, the mechanisms underlying the therapeutic effect of SGS in Hepatocellular carcinoma (HCC) are not completely clear. METHODS: The survival and metastasis of HCC cells were examined by CCK-8 assay, EdU assay, Wound-healing and Transwell assay. The anti-tumour effect of SGS was studied using hoechst 33258 staining and flow cytometry. RNA sequencing was applied to detect the underlying mechanism. Comet DNA, qRT-PCR and WB experiments were performed for validation. In addition, HCC nude mouse model was constructed to detect SGS effect in vivo. KEY FINDINGS: SGS inhibited the proliferation, migration and invasion of HCC cells and induced apoptosis in vitro. In addition, SGS also suppressed tumour growth in a nude mouse model of HCC in a dose-dependent manner. RNA sequencing of the suitably treated HCC cells revealed significant changes in the expression levels of genes involved in the DNA damage repair pathway. The sequencing results were verified by Comet DNA, qRT-PCR, WB assays and molecular docking. CONCLUSIONS: Taken together, SGS inhibits the malignant phenotype of HCC cells by down-regulating DNA repair genes and consequently inducing DNA damage.

Ectopic expression of two CAULIFLOWER genes from mango caused early flowering in Arabidopsis.

APETALA1 (AP1), CAULIFLOWER (CAL) and FRUITFULL (FUL) were homologous genes with redundant functions in the process of flower transformation and floral development in Arabidopsis. Two CALs genes, MiCAL1 and MiCAL2, were cloned from mango (Mangifera indica L.). Their full-length sequences contained 717 bp and 714 bp, encoding 239 and 238 amino acids, respectively. Both the MiCAL1 and MiCAL2 proteins contained typical MADS-box and K-box domains and therefore belonged to the CAL-like protein family. MiCAL1 and MiCAL2 were expressed in all tissues at the inflorescence elongation stage and flowering stage, with the highest expression in the leaves at the flowering stage. They had similar expression patterns during flower development, with the highest expression levels in leaves during flower differentiation and the lowest expression levels during fruit development. Overexpression of MiCAL1 and MiCAL2 resulted in significantly earlier flowering in Arabidopsis. Overexpression of MiCAL1 resulted in terminal flowers with normal flower organs, while overexpression of MiCAL2 induced partially variation in floral organs but had no effect on inflorescences. Yeast two-hybrid (Y2H) experiments showed that MiCAL1 and MiCAL2 can interact with several flower-related proteins as well as stress response proteins, such as SEP1, SVP1, SVP2, SOC1G and Di19-4. These results suggest that these two MiCALs genes may have an important influence on mango flowering.

Genome-Wide Analysis of the RNase T2 Family and Identification of Interacting Proteins of Four ClS-RNase Genes in 'XiangShui' Lemon.

S-RNase plays vital roles in the process of self-incompatibility (SI) in Rutaceae plants. Data have shown that the rejection phenomenon during self-pollination is due to the degradation of pollen tube RNA by S-RNase. The cytoskeleton microfilaments of pollen tubes are destroyed, and other components cannot extend downwards from the stigma and, ultimately, cannot reach the ovary to complete fertilisation. In this study, four S-RNase gene sequences were identified from the 'XiangShui' lemon genome and ubiquitome. Sequence analysis revealed that the conserved RNase T2 domains within S-RNases in 'XiangShui' lemon are the same as those within other species. Expression pattern analysis revealed that S3-RNase and S4-RNase are specifically expressed in the pistils, and spatiotemporal expression analysis showed that the S3-RNase expression levels in the stigmas, styles and ovaries were significantly higher after self-pollination than after cross-pollination. Subcellular localisation analysis showed that the S1-RNase, S2-RNase, S3-RNase and S4-RNase were found to be expressed in the nucleus according to laser confocal microscopy. In addition, yeast two-hybrid (Y2H) assays showed that S3-RNase interacted with F-box, Bifunctional fucokinase/fucose pyrophosphorylase (FKGP), aspartic proteinase A1, RRP46, pectinesterase/pectinesterase inhibitor 51 (PME51), phospholipid:diacylglycerol acyltransferase 1 (PDAT1), gibberellin receptor GID1B, GDT1-like protein 4, putative invertase inhibitor, tRNA ligase, PAP15, PAE8, TIM14-2, PGIP1 and p24beta2. Moreover, S3-RNase interacted with TOPP4. Therefore, S3-RNase may play an important role in the SI of 'XiangShui' lemon.

Evaluation of suspicious breast lesions with diffusion kurtosis MR imaging and connection with prognostic factors.

PURPOSE: To investigate the additional value of DKI in discriminating suspicious breast lesions on DCE-MRI, as compared with conventional DWI; and to explore connection between DKI-parameters and prognostic factors of breast cancers. METHODS: The institutional review board approved this retrospective study and written informed consent was waived. Totally, 300 women (mean age, 43.2 ± 10.4 years) with suspicious breast lesions on DCE-MRI were enrolled from November 2014 to September 2019. With pathology as reference, performance of ADC, Kapp and Dapp in discriminating suspicious breast lesions were analyzed by receiver operating characteristic (ROC) analysis with area under ROC curve (AUC). The specificities of parameters were compared by Chi-square test. The ADC, Kapp and Dapp of breast cancers with different receptor status were compared using Student's t or Mann-Whitney U or Kruskal-Wallis test. RESULTS: There were 344 suspicious breast lesions (220 malignant, 124 benign) in 300 women. No significant differences were found for AUCs of ADC and DKI-parameters in discriminating suspicious breast lesions (0.882 vs. 0.888, p = 0.480). The specificities were significantly higher with ADC and Dapp than that with DCE-MRI (p = 0.003 and 0.005). The ADC, Kapp and Dapp were correlated with HER2 expression and lymph node status, and ADC and Kapp differed between ER-positive and negative tumors (all p < 0.05). Except Kapp, DKI/DWI-parameters showed relation with Ki-67 expression. None of the DKI/DWI-parameters showed relation with lesion grade (all p > 0.05). CONCLUSION: The more complicated and time-consuming DKI is not superior to conventional DWI in differentiating suspicious breast lesions and reflecting prognostic information of breast cancer.

Prospective Study of Low- and Standard-dose Chest CT for Pulmonary Nodule Detection: A Comparison of Image Quality, Size Measurements and Radiation Exposure.

OBJECTIVE: To comprehensively and accurately analyze the out-performance of low-dose chest CT (LDCT) vs. standard-dose CT (SDCT). METHODS: The image quality, size measurements and radiation exposure for LDCT and SDCT protocols were evaluated. A total of 117 patients with extra-thoracic malignancies were prospectively enrolled for non-enhanced CT scanning using LDCT and SDCT protocols. Three experienced radiologists evaluated subjective image quality independently using a 5-point score system. Nodule detection efficiency was compared between LDCT and SDCT based on nodule characteristics (size and volume). Radiation metrics and organ doses were analyzed using Radimetrics. RESULTS: The images acquired with the LDCT protocol yielded comparable quality to those acquired with the SDCT protocol. The sensitivity of LDCT for the detection of pulmonary nodules (n=650) was lower than that of SDCT (n=660). There was no significant difference in the diameter and volume of pulmonary nodules between LDCT and SDCT (for BMI <22 kg/m2, 4.37 vs. 4.46 mm, and 43.66 vs. 46.36 mm3; for BMI ≥22 kg/m2, 4.3 vs. 4.41 mm, and 41.66 vs. 44.86 mm3) (P>0.05). The individualized volume CT dose index (CTDIvol), the size specific dose estimate and effective dose were significantly reduced in the LDCT group compared with the SDCT group (all P<0.0001). This was especially true for dose-sensitive organs such as the lung (for BMI <22 kg/m2, 2.62 vs. 12.54 mSV, and for BMI ≥22 kg/m2, 1.62 vs. 9.79 mSV) and the breast (for BMI <22 kg/m2, 2.52 vs. 10.93 mSV, and for BMI ≥22 kg/m2, 1.53 vs. 9.01 mSV) (P<0.0001). CONCLUSION: These results suggest that with the increases in image noise, LDCT and SDCT exhibited a comparable image quality and sensitivity. The LDCT protocol for chest scans may reduce radiation exposure by about 80% compared to the SDCT protocol.

Feasibility of Subtraction Coronary Computed Tomographic Angiography and Influencing Factor Analysis: a Retrospective Study.

OBJECTIVE: To investigate the feasibility of subtraction coronary computed tomographic (CT) angiography (SubCCTA) to decline calcium artifacts and improve diagnostic accuracy in the presence of coronary calcification and analyze the factors that influence SubCCTA. METHODS: A total of 294 patients suspected of having coronary artery diseases underwent coronary computed tomographic angiography (CCTA) and SubCCTA. Coronary stenoses were blindly evaluated by two experienced radiologists, which were compared with invasive coronary angiography (ICA). Multiple statistical indexes were adopted to analyze the value of SubCCTA for the diagnosis of calcium stenoses. RESULTS: The diagnosable rate of SubCCTA was 67.2% (n=197), and the non-diagnosable rate was 32.8% (n=97). Using SubCCTA, the false positive rate decreased from 56.5% to 17.4%, and the corresponding diagnostic accuracy was increased from 83.6% to 92.9%. Univariate logistic regression analysis showed that height (OR=1.029, 95% CI=1.001-1.058), weight (OR=1.025, 95% CI=1.004-1.046), left ventricular size (OR=1.018, 95% CI=1.007-1.030), cardiothoracic ratio (OR=39.917, 95% CI=1.244-1281.098), the average heart rate (OR=0.866, 95% CI=0.836-0.896) and heart rate range (OR=0.882, 95% CI=0.853-0.912) might be the factors influencing SubCCTA. CONCLUSION: This study suggested that SubCCTA could help improve diagnostic accuracy in the presence of calcium plaques. Moreover, several factors were discovered for the first time to possibly influence SubCCTA, which will be helpful in improving the subtracted image quality.

Detection and Classification of Breast Lesions With Readout-Segmented Diffusion-Weighted Imaging in a Large Chinese Cohort.

Objectives: To evaluate the performance of readout-segmented echo-planar imaging DWI (rs-EPI DWI) in detecting and characterizing breast cancers in a large Chinese cohort with comparison to dynamic contrast-enhanced MRI (DCE-MRI). Methods: The institutional review board approved this retrospective study with waived written informed consent. A total of 520 women (mean age, 43.1- ± 10.5-years) were included from July 2013 to October 2019. First, the ability of rs-EPI DWI in detecting breast lesions identified by DCE-MRI was evaluated. The lesion conspicuity of rs-EPI-DWI and DCE-MRI was compared using the Wilcoxon signed rank test. With pathology as a reference, the performance of rs-EPI DWI and DCE-MRI in distinguishing breast cancers was evaluated and compared using the Chi-square test. Results: Of 520 women, 327/520 (62.9%) patients had 423 lesions confirmed by pathology with 203 benign and 220 malignant lesions. The rs-EPI DWI can detect 90.8% (659/726) (reader 1) and 90.6% (663/732) (reader 2) of lesions identified by DCE-MRI. The lesion visibility was superior for DCE-MRI than rs-EPI-DWI (all p < 0.05). With pathology as a reference, the sensitivities and specificities of rs-EPI DWI in diagnosing breast cancers were 95.9% (211/220) and 85.7% (174/203) for reader 1 and 97.7% (215/220) and 86.2% (175/203) for reader 2. No significant differences were found for the performance of DCE-MRI and rs-EPI DWI in discriminating breast cancers (all p > 0.05). Conclusions: Although with an inferior lesion visibility, rs-EPI DWI can detect about 90% of breast lesions identified by DCE-MRI and has comparable diagnostic capacity to that of DCE-MRI in identifying breast cancer.

Fibrotic Changes Depicted by Thin-Section CT in Patients With COVID-19 at the Early Recovery Stage: Preliminary Experience.

Objectives: To analyze follow-up CTs of patients recovering from COVID-19 in Wuhan, focusing on fibrotic change and its relevant risk factors. Methods: From January 13 to February 27, 2020, 166 hospitalized patients meeting our criteria were included. The scores of fibrotic patterns on follow-up CT were evaluated. Patients were designated as group 1 (with CT evidence of fibrotic pattern) and group 2 (without CT evidence of fibrotic pattern). Multivariate logistic regression was performed to explore risk factors for fibrotic change in patients with COVID-19. Results: The follow-up CTs were obtained on 56 days (median, IQR 51-63 days) after symptom onset. Of the 166 patients (mean age, 57 ± 15 years; 69/166 male), 46% (76/166) had CT evidence of fibrotic change and 77% (127/166) were severe or critical cases. Among patients with fibrotic change on CT, 84% (64/76) got a minimal or mild score of fibrosis. The high total score on peak CT, peak eosinophils, erythrocyte sedimentation rate (ESR) and advancing age were related to lung fibrotic change in patients with COVID-19. Conclusion: Forty six percentages of patients (mainly severe or critical cases) with COVID-19 showed fibrotic change on follow-up CT at early recovery phase, while the extent of fibrosis was not large. The advancing age, high total score on peak CT, peak eosinophils and ESR were associated with fibrotic change depicted by CT in patients recovering from COVID-19. An extended follow up by CT imaging and pulmonary function testing is necessary to fully assess the sequela of COVID-19.

Erratum: The MAPKKK CgMck1 Is Required for Cell Wall Integrity, Appressorium Development, and Pathogenicity in Colletotrichum gloeosporioides (Genes 2018, 9, 543).

The authors wish to make the following correction to this paper [...].