Explore the vast range of titles available.

TR3 is an orphan nuclear receptor with roles in apoptosis. A TR3-binding compound induces mitochondrial translocation of TR3 and autophagy via the Nix–Toms–ANT1/VDAC1 pathway, providing a mechanism for cell death in melanoma cells that are resistant to spontaneous and drug-induced apoptosis. Autophagy is linked to cell death, yet the associated mechanisms are largely undercharacterized. We discovered that melanoma, which is generally resistant to drug-induced apoptosis, can undergo autophagic cell death with the participation of orphan nuclear receptor TR3. A sequence of molecular events leading to cellular demise is launched by a specific chemical compound, 1-(3,4,5-trihydroxyphenyl)nonan-1-one, newly acquired from screening a library of TR3-targeting compounds. The autophagic cascade comprises TR3 translocation to mitochondria through interaction with the mitochondrial outer membrane protein Nix, crossing into the mitochondrial inner membrane through Tom40 and Tom70 channel proteins, dissipation of mitochondrial membrane potential by the permeability transition pore complex ANT1–VDAC1 and induction of autophagy. This process leads to excessive mitochondria clearance and irreversible cell death. It implicates a new approach to melanoma therapy through activation of a mitochondrial signaling pathway that integrates a nuclear receptor with autophagy for cell death.

Objective To investigate the effects of Pien Tze Huang (PZH) on the migration and invasion of HCC cells and underlying molecular mechanism. Methods Cell counting kit-8 (CCK-8) was applied to evaluate the cell viabilities of SMMC-7721, SK-Hep-1, C3A and HL-7702 (6 × 10 3 cells/well) co-incubated with different concentrations of PZH (0, 0.2, 0.4, 0.6, 0.8 mg/mL) for 24 h. Transwell, wound healing assay, CCK-8 and Annexin V-FITC/PI staining were conducted to investigate the effects of PZH on the migration, invasion, proliferation and apoptosis of SK-Hep-1 and SMMC-7721 cells (650 µ g/mL for SK-Hep-1 cells and 330 µ g/mL for SMMC-7721 cells), respectively. In vivo , lung metastasis mouse model constructed by tail vein injection of HCC cells was used for evaluating the anti-metastasis function of PZH. SK-Hep-1 cells (10 6 cells/200 µ L per mice) were injected into B-NDG mice via tail vein. Totally 8 mice were randomly divided into PZH and control groups, 4 mice in each group. After 2-d inoculation, mice in the PZH group were administered with PZH (250 mg/kg, daily) and mice in the control group received only vehicle (PBS) from the 2nd day after xenograft to day 17. Transcriptome analysis based on RNA-seq was subsequently used for deciphering anti-tumor mechanism of PZH. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were applied to verify RNA-seq results. Luciferase reporter assay was performed to examine the transcriptional activity of yes-associated protein (YAP). Results PZH treatment significantly inhibited the migration, invasion, proliferation and promoted the apoptosis of HCC cells in vitro and in vivo ( P <0.01). Transcriptome analysis indicated that Hippo signaling pathway was associated with anti-metastasis function of PZH. Mechanical study showed PZH significantly inhibited the expressions of platelet derived growth factor receptor beta (PDGFRB), YAP, connective tissue growth factor (CCN2), N-cadherin, vimentin and matrix metallopeptidase 2 (MMP2, P <0.01). Meanwhile, the phosphorylation of YAP was also enhanced by PZH treatment in vitro and in vivo. Furthermore, PZH played roles in inhibiting the transcriptional activity of YAP. Conclusion PZH restrained migration, invasion and epithelial-mesenchymal transition of HCC cells through repressing PDGFRB/YAP/CCN2 axis.

Angiotensin II (AngII) induces cardiac hypertrophy and increases the expression of TR3. To determine whether TR3 is involved in the regulation of the pathological cardiac hypertrophy induced by AngII, we established mouse and rat hypertrophy models using chronic AngII administration. Our results reveal that a deficiency of TR3 in mice or the knockdown of TR3 in the left ventricle of rats attenuated AngII‐induced cardiac hypertrophy compared with the respective controls. A mechanistic analysis demonstrates that the TR3‐mediated activation of mTORC1 is associated with AngII‐induced cardiac hypertrophy. TR3 was shown to form a trimer with the TSC1/TSC2 complex that specifically promoted TSC2 degradation via a proteasome/ubiquitination pathway. As a result, mTORC1, but not mTORC2, was activated; this was accompanied by increased protein synthesis, enhanced production of reactive oxygen species and enlarged cell size, thereby resulting in cardiac hypertrophy. This study demonstrates that TR3 positively regulates cardiac hypertrophy by influencing the effect of AngII on the mTOR pathway. The elimination or reduction of TR3 may reduce cardiac hypertrophy; therefore, TR3 is a potential target for clinical therapy. Graphical Abstract Persistent cardiac hypertrophy ultimately leads to cardiovascular disease. Here, the authors show that the nuclear receptor TR3 participates in angiotensin‐induced cardiac hypertrophy by controlling mTORC1 signaling.

MDM2 is an oncoprotein whose transforming potential is activated by overexpression. The expression level of MDM2 is negatively regulated by orphan receptor TR3 that mainly acts as a transcriptional factor to regulate gene expression. However, the underlying mechanism is largely unclear. Here, we present the first evidence that inhibition of TR3 on MDM2 is mediated by p53. We found that TR3 directly interacts with p53 but not MDM2, and such interaction is critical for TR3 to inhibit MDM2 expression. TR3 downregulates p53 transcriptional activity by blocking its acetylation, leading to a decrease on the transcription level of MDM2. Furthermore, TR3 binding to p53 obstructs its ubiquitination and degradation induced by MDM2, resulting in the MDM2 ubiquitination and degradation. In addition, TR3 could enhance p53‐mediated apoptosis induced by UV irradiation. Taken together, our findings demonstrate that p53 mediates the suppression of TR3 on MDM2 at both transcriptional and post‐transcriptional level and suggest TR3 as a potential target to develop new anticancer agents that restrict MDM2‐induced tumor progression.

Objective： This study aims to explore the clinicopathologic characteristics and prognostic factors of gastric cancer patients with metachronous ovarian metastasis. Methods： Clinicopathologic data were collected from 63 post-operative gastric cancer patients with metachronous ovarian metastasis. The patients were admitted to the Cancer Institute and Hospital, Chinese Academy of Medical Science and Peking Union Medical College between January 1999 and December 2011. A log-rank test was conducted for survival analysis. Possible prognostic factors that affect survival were examined by univariate analysis. A Cox regression model was used for multivariate analysis. Results： The incidence of ovarian metastasis was 3.4% with a mean age of 45 years. Up to 65.1% of the patients were pre- menopausal. The mean interval between ovarian metastasis and primary cancer was 16 months. Lowly differentiated carcinoma ranked first in the primary gastric cancers. The majority of lesions occurred in the serous membrane （87.3%）. The metastatic sites included Nz.3 lymph nodes （68.3%）, bilateral ovaries （85.7%）, and peritoneal membrane （73%）. Total resection of metastatic sites was performed （31.7%）. The overall median survival was 13.6 months, whereas the overall 1-, 2-, and 3-year survival rates were 52.5%, 22.0%, and 9.8%, respectively. The 5-year survival rate was zero. Univariate analysis showed that the patient prognosis was correlated with metastatic peritoneal seeding, vascular tumor embolus, range of lesion excision, and mode of comprehensive treatment with adjuvant chemotherapy （P〈0.05）. Multivariate analysis indicated that metastatic peritoneal seeding was an independent prognostic factor for gastric cancer patients with ovarian metastasis （P〈0.01）. Conclusion： Effective control of peritoneal seeding--induced metastasis is important for improving the prognosis of gastric cancer patients with ovarian metastasis.

Background：Conflicting results about the association between expression level of excision repair cross-complementation group 1 （ERCC1） and clinical outcome in patients with colorectal cancer （CRC） receiving chemotherapy have been reported.Thus,we searched the available articles and performed the meta-analysis to elucidate the prognostic role of ERCC1 expression in patients with CRC.Methods：A thorough literature search using PubMed （Medline）,Embase,Cochrane Library,Web of Science databases,and Chinese Science Citation Database was conducted to obtain the relevant studies.Pooled hazard ratios （HRs） or odds ratios （ORs） with 95% confidence intervals （CIs） were calculated to estimate the results.Results：A total of 11 studies were finally enrolled in this meta-analysis.Compared with patients with lower ERCC1 expression,patients with higher ERCC1 expression tended to have unfavorable overall survival （OS） （HR =2.325,95% CI：1.720-3.143,P 〈 0.001）,progression-free survival （PFS） （HR =1.917,95% CI：1.366-2.691,P 〈 0.001） and poor response to chemotherapy （OR =0.491,95% CI：0.243-0.990,P =0.047）.Subgroup analyses by treatment setting,ethnicity,HR extraction,detection methods,survival analysis,and study design demonstrated that our results were robust.Conclusions：ERCC1 expression may be taken as an effective prognostic factor predicting the response to chemotherapy,OS,and PFS.Further studies with better study design and longer follow-up are warranted in order to gain a deeper understanding of ERCC 1＇s prognostic value.

Objective To evaluate the relationship between dietary intake and risk of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) while controlling for human papillomavirus (HPV) infection. Methods In 1999 and 2002, 11,031 women aged 35–50, were screened as part of two cross-sectional population-based cervical cancer screening studies in China. Dietary food intake information was collected by a 79-item Food Frequency Questionnaire (FFQ). 748 HPV-positive women (557 normal biopsy; 95 CIN2, 79 CIN3 and 17 cancer) with completed interviews and biopsy results were included in our data analysis. Specific dietary food groups were classified into dark-colored vegetables, light-colored vegetables, onion vegetables, legumes, nuts, eggs, and meat. Unconditional logistic regression was used to evaluate the association between dietary intake and the risk of developing CIN2+. Results Inverse associations between CIN2+ risk and onion vegetables, legumes, nuts, and meat were observed. Comparison of the lowest and highest tertiles for consumption of onion vegetables, legumes, nuts, and meat yielded adjusted odds ratios (ORs) of 0.589 [95% confidence intervals (CI), 0.387–0.897; P for trend = 0.011], 0.591 (95% CI, 0.392–0.892; P for trend = 0.012), 0.635 (95% CI, 0.426–0.946; P for trend = 0.019), 0.624 (95% CI, 0.406–0.958; P for trend = 0.044), respectively, for CIN2+ risk among 748 HPV-positive women. No associations were found between CIN2+ risk and dark-colored vegetables, light-colored vegetables or eggs. Conclusions Dietary intake of onion vegetables, legumes, nuts, and meat is associated with reduced risk of CIN2+. These foods may provide a protective factor against CIN2+.

Background Current guidelines recommend pelvic lymphadenectomy (PLND) for patients with pelvic lymph node metastasis and special state. However, these data and recommendations do not distinguish the role of PLND in different patient groups and confirm the final benefits. The aim of this study was to confirm the efficacy of pelvic lymphadenectomy (PLND) for the different groups of patients. Methods Data obtained from 7 centers were retrospectively analyzed. Of the patients, 190 pN2-3 penile carcinoma patients confirmed by bilateral inguinal lymph node excision were included in this study. Sixty-nine and 121 of these patients did and did not undergo bilateral PLND, respectively. The baseline differences from the patients were matched by propensity score analysis. Results In this study, the Kaplan–Meier estimated disease-specific survival (DSS) was not significantly different between the PLND and no-PLND groups ( P  = 0.796). According to the propensity score matching for T stage, N stage, grade, adjuvant therapies, and lymph node stage (number of inguinal lymph node metastasis and extranodal extension), 48 patients were selected for each group. Among the pN2 patients, the PLND group showed higher DSS rates than the no-surgery group ( P  = 0.030). However, even after matching, survival did not differ between the PLND and no-PLND patients among all patients ( P  = 0.609) and pN3 patients ( P  = 0.417) with comparable DSS. Conclusion Bilateral PLND may improve survival in pN2 patients. Men with pN3 may not benefit from bilateral PLND.

The existing image steganography methods either sequentially conceal secret images or conceal a concatenation of multiple images. In such ways, the interference of information among multiple images will become increasingly severe when the number of secret images becomes larger, thus restrict the development of very large capacity image steganography. In this paper, we propose an Invertible Mosaic Image Hiding Network (InvMIHNet) which realizes very large capacity image steganography with high quality by concealing a single mosaic secret image. InvMIHNet consists of an Invertible Image Rescaling (IIR) module and an Invertible Image Hiding (IIH) module. The IIR module works for downscaling the single mosaic secret image form by spatially splicing the multiple secret images, and the IIH module then conceal this mosaic image under the cover image. The proposed InvMIHNet successfully conceal and reveal up to 16 secret images with a small number of parameters and memory consumption. Extensive experiments on ImageNet-1K, COCO and DIV2K show InvMIHNet outperforms state-of-the-art methods in terms of both the imperceptibility of stego image and recover accuracy of secret image.

By the spherical wave spectrum transform, the sound pressures on the two spherical surfaces surrounding the scattering objects with arbitrarily-shaped surfaces are decomposed into spherical wave components that propagate in a known manner, the relationships between the spherical wave components of the same order on the two spherical surfaces are established by the wave field extrapolation theorem, and the formula of the separation theory in the spherical coordinate is established in the wave-number domain. After separating the scattered pressure, the total scattered field can be obtained by holographic reconstruction and prediction. In order to overcome the instability of acoustic inverse problem, a new wave-number domain filter technique is proposed. It is proved that, as long as the two holographic spherical surfaces are taken to be close enough, the singularity of the separation formula can be avoided. The results of numerical simulation demonstrate the feasibility and validity of the separation theory.