Search

Summary: Magnetic resonance imaging (MRI) is a widely used imaging modality in clinics for medical disease diagnosis, staging, and follow-up. Deep learning has been extensively used to accelerate k-space data acquisition, enhance MR image reconstruction, and automate tissue segmentation. However, these three tasks are usually treated as independent tasks and optimized for evaluation by radiologists, thus ignoring the strong dependencies among them; this may be suboptimal for downstream intelligent processing. Here, we present a novel paradigm, full-stack learning (FSL), which can simultaneously solve these three tasks by considering the overall imaging process and leverage the strong dependence among them to further improve each task, significantly boosting the efficiency and efficacy of practical MRI workflows. Experimental results obtained on multiple open MR datasets validate the superiority of FSL over existing state-of-the-art methods on each task. FSL has great potential to optimize the practical workflow of MRI for medical diagnosis and radiotherapy.

Development of docetaxel (TXT) resistance is a major obstacle for triple-negative breast cancer (TNBC) treatment. Additionally, chemoresistant cell-derived exosomes were able to change the chemo-response of chemosensitive recipient cells via transportation of lncRNAs. It has been shown that lncRNA LINC00667 level was significantly elevated in breast cancer tissues. Therefore, we explored whether LINC00667 level is increased in TXT-resistant TNBC cell-derived exosomes. In addition, whether exosomal LINC00667 derived from TXT-resistant TNBC cell could affect TXT sensitivity in TXT-sensitive TNBC cells was investigated as well. In the present study, exosomes were isolated from the TXT-resistant TNBC cells and from TXT-sensitive TNBC cells. Next, the level of LINC00667 in the isolated exosomes was detected with RT-qPCR. We found that LINC00667 expression was obviously elevated in TXT-resistant TNBC cell-derived exosomes compared to that in TXT-sensitive TNBC cell-derived exosomes. In addition, LINC00667 could be transferred from TXT-resistant TNBC cells to TNBC cells via exosomes. Moreover, TXT-resistant TNBC cell secreted exosomal LINC00667 markedly reduced the sensitivity of TNBC cells to TXT via upregulation of Bcl-2. Meanwhile, downregulation of LINC00667 notably enhanced the sensitivity of TXT-resistant TNBC cells to TXT through downregulation of Bcl-2. Additionally, LINC00667 was considered to be a ceRNA to sponge miR-200b-3p, thereby elevating Bcl-2 expression. Collectively, TXT-resistant TNBC cell-derived exosomal LINC00667 could decrease the chemosensitivity of TNBC cells to TXT via regulating miR-200b-3p/Bcl-2 axis. These findings suggested that LINC00667 might serve as a promising target for enhancing sensitivity of TNBC cells to TXT therapy.

Objective This study was conducted to explore the appropriate radical radiation dose in concurrent chemoradiotherapy (CCRT) for patients with inoperable stage II–III esophageal squamous cell carcinoma (ESCC). Methods This retrospective study included patients with esophageal cancer (EC) from the database of patients treated at the Affiliated Zhangjiagang Hospital of Soochow University (1/2015–12/2019). Overall survival (OS), progression-free survival (PFS), objective remission rate (ORR), first failure pattern, and toxicities were collected. Results 112 patients treated with intensity-modulated radiation therapy (IMRT) combined with concurrent chemotherapy of nedaplatin-based regimens were included. Fifty-eight (51.8%) and 54 (48.2%) patients received 60 (HD) and 50.4 (LD) Gy of radiotherapy, respectively. The HD group showed superior OS and a trend for longer PFS compared with the LD group (median OS: 25.5 vs 17.5 months, P = .021; median PFS: 14.0 vs 10.5 months, P = .076). There were more patients with a complete remission (CR) in the HD group than in the LD group (P=.016). The treatment-related toxicities were generally acceptable, but HD radiotherapy would increase the incidence of grade ≥3 late radiotoxicity (22.4% vs 5.6%, P = .011). Conclusion In nedaplatin-based CCRT for stage II–III ESCC, the radiotherapy dose of 60 Gy achieved a better prognosis. Strengths and limitations of this study A comparative study of 50.4 Gy and 60 Gy was conducted to evaluate whether 50.4 Gy can be used as a radical radiotherapy dose for inoperable stage II–III esophageal squamous cell carcinoma from a real-world perspective. The highly consistent selection criteria in our study make analysis results highly reliable and scientific. The existing research results support that nedaplatin can be used in concurrent chemoradiotherapy for esophageal squamous cell carcinoma, and this study focuses on the discovery of a better nedaplatin-based combination regimen. The findings of this study are limited to a single-center study with a non-large sample size. Inevitably, recall bias may exist in this retrospective study. Surgery was not involved in the follow-up treatment after concurrent chemoradiotherapy, which may worsen the prognosis of some patients.

Proteins in the tripartite motif-containing protein (TRIM) family participates in carcinogenesis. However, little attention was focused on the role of TRIM6 on development of breast cancer. Expression level of TRIM6 was found to be markedly enhanced in breast cancer cells and tissues. Functional assays demonstrated that overexpression of TRIM6 promoted breast cancer progression through increase of YAP1 (Yes-associated Protein 1), while knockdown of TRIM6 suppressed in vitro breast cancer progression and in vivo tumor growth through decrease of YAP1. Co-Immunoprecipitation (co-IP) showed that TRIM6 interacted with STUB1 (stress induced phosphoprotein 1 homology and U-box containing protein 1). TRIM6 promoted ubiquitination-mediated degradation of STUB1 to promote YAP1 signaling. Overexpression of STUB1 attenuated TRIM6-induced promotion of breast cancer growth. In conclusion, TRIM6 contributed to breast cancer progression through ubiquitination-dependent proteasomal degradation of STUB1 and provocation of YAP1 pathway, providing potential therapeutic target for breast cancer.

Background/Aims: Gastric neuroendocrine tumors (G-NETs) are uncommon neoplasms that can present with or without clinical symptoms. In this study, we evaluated the incidence, prognosis, and temporal trends of G-NETs. Methods: We analyzed all cases of G-NETs registered in the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2014. Incidence was estimated by age and joinpoint analyses. Survival rates were calculated and survival trends over time were evaluated. Results: A total of 3740 eligible patients were enrolled in the study. G-NETs incidence increased from 0.31 per 1 000 000 patients in 1975 to 4.85 in 2014, with an annual percentage changes (APCs) of 8.9% (95% confidence interval [CI] = 7.7% to 10.21%, P < 0.001, t test (29) from 1975 to 2001 and 3.6% from 2002 to 2014 (95% CI= 2.3% to 4.9%, P < 0.001). For cases diagnosed between 1973 and 1982, five-year survival was 62.8% ± 7.0% (Standard error, SE) and increased to 86.7% ± 0.7% for cases diagnosed between 2003 and 2012 (P < 0.001). Years of diagnosis, gender, age at diagnosis, marital status, grade, tumor size, tumor stage, and surgery performed or not were the strongest predictors of worse survival in both univariate and multivariate analysis (P

The output LC filter of a photovoltaic (PV) string three-level grid-tied inverter that connects the filter capacitor neutral point to dc-link capacitor neutral point can reduce the common-mode (CM) current injected to the grid by letting the CM current circulate within the inverter. However, the internal CM current may resonate because of the existence of the resonant frequency of the internal CM LC circuit. Compared with the traditional continuous pulse-width modulation (CPWM), the resonance can be worse if discontinuous pulse-width modulation (DPWM) is applied, for the zero sequence quantity of DPWM contains more harmonics than that of CPWM. In this paper, a virtual negative resistor based common mode current resonance suppression method for a three-level grid-tied inverter is proposed to overcome the CM current resonance problem in DPWM application. Different positions of the virtual negative resistor in the equivalent CM circuit with different feedback variables are analyzed theoretically. The virtual negative resistor connected in series with the inductor in the equivalent CM circuit is selected to damp the CM current resonance for simplification and damping performance. Different from the implementation in CPWM where a pair of small voltage vectors exist and are used to adjust the CM voltage directly, the proposed method for DPWM application is implemented indirectly by adding the CM adjustment quantity to differential-mode (DM) control quantity with appropriate coefficients. Depending on the sector of DM control quantity in the α β reference frame, the coefficients are calculated using one of three specific voltage vectors. Experimental results are given to demonstrate the effectiveness of theoretical analyses and the proposed method.

Abstract Background Energy balance has long been known to extend lifespans and inhibit carcinogenesis in multiple species by slowing age‐related epigenetic changes while the underlying mechanisms remain largely unknown. Herein, we found that starvation activated autophagy to remodel the DNA methylation profile by inhibiting DNMT3a expression. Methods Illumina Infinium MethylationEPIC BeadChip and dot blot assay were performed to quantify the global DNA methylation level. Protein−RNA interactions were validated through RNA immunoprecipitation and RNA pull‐down assay. In vitro and in vivo experiments were carried out to testify the effect of DNMT3a on chemoresistance. Results Autophagy is impaired in chemoresistance which was associated with differential DNA methylation and could be reversed by DNMT3a inhibition. Autophagy activation decreases the expression of DNMT3a mRNA, accompanied with the downregulation of chemoresistance‐related Linc00942. Knockdown of Linc00942 reduces DNMT3a expression and genome‐wide DNA methylation while Linc00942 overexpression increased DNMT3a expression and correlated hypermethylation in cancer cells and primary tumour tissues. Mechanistically, Linc00942 recruits RNA methyltransferase METTL3 to stimulate N6‐methyladenosine (m6A) deposit on DNMT3a transcripts, triggering IGF2BP3/HuR to recognize modified mRNA for reinforced stability. SQSTM1/p62 recruits Linc00942 for autophagic degradation which can be abrogated after autophagy inhibition by p62 knockdown or chloroquine treatment. Conclusions Inhibition of autophagy increases Linc00942 expression to promote chemoresistance and autophagy activation or hypomethylating agent decitabine restores chemosensitivity by reducing global DNA methylation. Overall, this study identifies a novel methylation cascade linking impaired RNautophagy to global hypermethylation in chemoresistance, and provides a rationale for repurposing decitabine to overcome chemoresistance in cancer treatment.

The thermal creep forming and thermo-hydrogen processing of titanium alloys have been used in industry production. The combination of these methods is a potential way to improve the plasticity of titanium alloys and the formability of complex components. The effect of hydrogen addition on high temperature creep behavior of Ti-6Al-4V alloy was investigated by creep tests and microstructural observations. The results show that β/α phase ratio increases with hydrogen content while α′ and αʺ martensites continuously precipitate in β phase. The α/β or α/α phase boundaries become wider. Hydrogen can promote creep rate through softening effect during primary and steady creep stage. However, the embrittlement happens in the tertiary creep stage. The hydrogenated alloy is more sensitive to initial stress and creep temperature. The creep strain of hydrogenated alloy with 0.2 wt%H is similar to that of as-received one. Meanwhile, the creep strain of hydrogenated alloy with 0.4 wt%H significantly decreases. Besides, the smaller initial stress is beneficial to obtain the larger creep strain.

Abstract Background Basal/human epidermal growth factor receptor (HER)2-positive (HER2+) breast cancer is resistant to monoclonal antibody (herceptin) treatment. There are currently only three basal/HER2+ breast cancer cell lines available, but they are not from Chinese populations. Methods Three immortalized cell lines (ZJU-0327, ZJU-0725, and ZJU-1127) were established from invasive ductal breast carcinoma tissue of two patients treated by surgical resection at our center. The cell lines were characterized in terms of histology, therapeutic response, and biomarker expression. Their tumorigenic potential was evaluated in an athymic nude (BALB/C nu) mouse xenograft model. Cell authentication testing by the techniques of short tandem repeat. Results ZJU-0327, ZJU-0725, and ZJU-1127 cell lines were maintained for more than 110 passages in vitro. The cells grew as monolayers; showed typical epithelial morphology and ultrastructure; were polyploid; had doubling times of 18, 57.5, and 18 h, respectively; had a near-tetraploid (ZJU-0327 and ZJU-1127) or aneuploid (ZJU-0725) karyotype with structural aberrations and tumor protein 53 mutation; insensitive to chemotherapeutic drugs and/or radiation; show high invasiveness and tumorigenicity in mice; and had no mycoplasma contamination. The cell lines were basal/HER2+, expressed cluster of differentiation, and were associated with poor prognosis. Cell authentication testing by the American Type Culture Collection confirmed the human origin of the cell lines, which did not match those in existing databases. Conclusions The three novel basal/HER2+ breast cancer cell lines recapitulating the malignant characteristics of the parent tumor’s, and can be useful for clarifying the molecular pathogenesis of basal/HER2+ breast cancer.

paper aims at working out analysis model of risk coupling for rural tourism safety accidents. First, based on the regional environmental risk system theory, the rural tourism safety system is analyzed. Second, under the four dimension of man, machine, environment, and management, the diamond model is established for rural tourism safety risk. Then, based on connotation of coupling, the definition and types of risk coupling was given for rural tourism safety accidents. Finally, based on the periphery theory and trigger working principle, a risk coupling mechanism model of rural tourism safety was established according to the “rural tourism risk trigger”. The results may give countermeasures and suggestions to risk management of rural tourism safety.