STAT5A modulates gastric cancer progression via upregulation of CD44.

OBJECTIVE: Signal transduction and transcriptional activator 5A (STAT5A), which has been reported to be frequently phosphorylated in tumors, plays pivotal roles in tumor progression. However, the role of STAT5A in gastric cancer (GC) progression and the downstream targets of STAT5A remain largely unknown. METHODS: The expression of STAT5A and CD44 were assessed. GC cells were treated with altered STAT5A and CD44 to evaluate their biological functions. Nude mice were given injections of genetically manipulated GC cells and growth of xenograft tumors and metastases was measured. RESULTS: The increased level of p-STAT5A is associated with tumor invasion and poor prognosis in GC. STAT5A promoted GC cell proliferation by upregulating CD44 expression. STAT5A directly binds to the CD44 promoter and promotes its transcription. CONCLUSIONS: The STAT5A/CD44 pathway plays a critical role in GC progression, promising potential clinical applications for improving treatment of GC.

Observation of Phonon Cascades in Cu-Doped Colloidal Quantum Wells.

Electronic doping has endowed colloidal quantum wells (CQWs) with unique optical and electronic properties, holding great potential for future optoelectronic device concepts. Unfortunately, how photogenerated hot carriers interact with phonons in these doped CQWs still remains an open question. Here, through investigating the emission properties, we have observed an efficient phonon cascade process (i.e., up to 27 longitudinal optical phonon replicas are revealed in the broad Cu emission band at room temperature) and identified a giant Huang-Rhys factor (S ≈ 12.4, more than 1 order of magnitude larger than reported values of other inorganic semiconductor nanomaterials) in Cu-doped CQWs. We argue that such an ultrastrong electron-phonon coupling in Cu-doped CQWs is due to the dopant-induced lattice distortion and the dopant-enhanced density of states. These findings break the widely accepted consensus that electron-phonon coupling is typically weak in quantum-confined systems, which are crucial for optoelectronic applications of doped electronic nanomaterials.

Treatment of Complex Renal Calculi by Digital Flexible Ureterorenoscopy Combined with Single-Tract Super-Mini Percutaneous Nephrolithotomy in Prone Position: A Retrospective Cohort Study.

BACKGROUND Advances in percutaneous nephrolithotomy (PCNL) have resulted in smaller devices that cause less trauma and bleeding, while flexible ureterorenoscopy (f-URS) allows access to any calyces. These methods are often used in isolation, but used in combination they may improve treatment of complex renal calculi. This study assessed the effectiveness and complications of f-URS combined with super-mini-PCNL (SMP) to treat complex renal calculi. MATERIAL AND METHODS A retrospective cohort analysis was made of patients with unilateral complex renal stones treated between March 2013 and December 2016. Patients were grouped according to surgical procedure: SMP (SMP Group), f-URS holmium laser lithotripsy (f-URS Group), and combined SMP and f-URS (Combined Group). The postoperative complications and complete stone-free rate were analyzed and compared among the 3 groups. RESULTS A total of 140 patients with complex renal stones were included: 40 patients in the SMP Group, 55 in the f-URS Group, and 45 in the Combined Group. The complete stone-free rate 3 days after the procedure was 77.5% in the SMP Group, 78.2% in the f-URS Group, and 97.8% in the Combined Group (p=0.010). The operation time, intraoperative blood loss, and hospitalization time of the Combined Group were all significantly lower than those in the SMP Group but higher than those in the f-URS Group. The follow-up was 9 months (range, 6-12 months). There were no medium-term complications reported. CONCLUSIONS SMP combined with f-URS holmium laser lithotripsy in the prone position is an effective treatment for complex renal calculi.

Classification of cervical lesions based on multimodal features fusion.

Cervical cancer is a severe threat to women's health worldwide with a long cancerous cycle and a clear etiology, making early screening vital for the prevention and treatment. Based on the dataset provided by the Obstetrics and Gynecology Hospital of Fudan University, a four-category classification model for cervical lesions including Normal, low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL) and cancer (Ca) is developed. Considering the dataset characteristics, to fully utilize the research data and ensure the dataset size, the model inputs include original and acetic colposcopy images, lesion segmentation masks, human papillomavirus (HPV), thinprep cytologic test (TCT) and age, but exclude iodine images that have a significant overlap with lesions under acetic images. Firstly, the change information between original and acetic images is introduced by calculating the acetowhite opacity to mine the correlation between the acetowhite thickness and lesion grades. Secondly, the lesion segmentation masks are utilized to introduce prior knowledge of lesion location and shape into the classification model. Lastly, a cross-modal feature fusion module based on the self-attention mechanism is utilized to fuse image information with clinical text information, revealing the features correlation. Based on the dataset used in this study, the proposed model is comprehensively compared with five excellent models over the past three years, demonstrating that the proposed model has superior classification performance and a better balance between performance and complexity. The modules ablation experiments further prove that each proposed improved module can independently improve the model performance.

The prognostic value and its relationship with immune infiltration of ACLY in clear cell renal cell carcinoma.

ATP citrate lyase (ACLY) is activated in various cancers, but its role in clear cell renal cell carcinoma (ccRCC) remains poorly understood. Herein, we investigated the prognostic role and potential mechanism of ACLY in ccRCC. The expression profile of ACLY in ccRCC was explored using Gene Expression Profiling Interactive Analysis 2 (GEPIA2), Gene Expression Omnibus (GEO), UALCAN and western blotting assays. The prognosis was investigated using immunohistochemistry (IHC) and Kaplan-Meier plotter assays. The relationship with immune infiltration was further evaluated using Tumor Immune Estimation Resource 2 (TIMER2) and Tumor Immune System Interactions and DrugBank (TISIDB) databases, respectively. Further biological function of ACLY in ccRCC pathogenesis was explored using in vitro experiments. ACLY level was higher in ccRCC than adjacent kidney tissues, and Kaplan-Meier survival analysis showed ACLY mRNA or protein were predictors of poor prognosis in ccRCC patients. Importantly, we reported for the first time that ACLY gene expression was significantly correlated with numerous immune cells and immune inhibitors in ccRCC. ACLY inhibition significantly impaired cell proliferation, induced cell apoptosis, attenuated cell migration, decreased lipid droplets formation, and suppressed epithelial-mesenchymal transition (EMT) of ccRCC. Moreover, these effects might be acted through mammalian target of rapamycin complex 1 (mTORC1) pathway. Collectively, ACLY was not only implicated in ccRCC tumorigenesis and progression, but also potentially interacted with immune infiltration and mTORC1 pathway. Our findings may provide a novel therapeutic strategy by targeting ACLY for ccRCC treatment.

An improvement method for pancreas CT segmentation using superpixel-based active contour.

Objective.Pancreas is one of the most challenging organs for Computed Tomograph (CT) image automatic segmentation due to its complex shapes and fuzzy edges. It is simple and universal to use the traditional segmentation method as a post-processor of deep learning method for segmentation accuracy improvement. As the most suitable traditional segmentation method for pancreatic segmentation, the active contour model (ACM), still suffers from the problems of weak boundary leakage and slow contour evolution speed. Therefore, a convenient post-processor for any deep learning methods using superpixel-based active contour model (SbACM) is proposed to improve the segmentation accuracy.Approach.Firstly, the superpixels with strong adhesion to edges are used to guide the design of narrowband and energy function. A multi-scale evolution strategy is also proposed to reduce the weak boundary leakage and comprehensively improve the evolution speed. Secondly, using the original image and the coarse segmentation results obtained from deep learning methods as inputs, the proposed SbACM method is used as a post-processor for fine segmentation. Finally, the pancreatic segmentation public dataset TCIA from the National Institutes of Health(NIH, USA) is used for evaluation, and the Wilcoxon Test confirmed that the improvement of proposed method is statistically significant.Main results.(1) the superpixel-based narrowband shape and dynamic edge energy of the proposed SbACM work for boundary leakage reduction, as well as the multi-scale evolution strategy and dynamic narrowband width for the evolution speed improvement; (2) as a post-processor, SbACM can increase the Dice similarity coefficients (DSC) of five typical UNet-based models, including UNet, SS-UNet, PBR UNet, ResDSN, and nnUNet, 2.35% in average and 9.04% in maximum. (3) Based on the best backbone nnUNet, the proposed post-processor performs better than either adding edge awareness or adding edge loss in segmentation enhancement without increasing the complexity and training time of deep learning models.Significance.The proposed SbACM can improve segmentation accuracy with the lowest cost, especially in cases of squeezed fuzzy edges with similar neighborhood , and complex edges.

High-security automatic path planning of radiofrequency ablation for liver tumors.

BACKGROUND AND OBJECTIVE: Radiofrequency ablation (RFA) is an effective method for the treatment of liver tumors. Preoperative path planning, which plays a crucial role in RFA treatment, requires doctors to have significant experience and ability. Specifically, correct and highly active preoperative path planning should ensure the safety of the whole puncturing process, complete ablation of tumors and minimal damage to healthy tissues. METHODS: In this paper, a high-security automatic multiple puncture path planning method for liver tumors is proposed, in which the optimization of the ablation number, puncture number, target positions and puncture point positions subject to comprehensive clinical constraints are studied. In particular, both the safety of the puncture path and the distribution of ablation ellipsoids are taken into consideration. The influence of each constraint on the safety of the whole puncturing process is discussed in detail. On this basis, the efficiency of the planning method is obviously improved by simplifying the computational data and optimized variables. In addition, the performance and adaptability of the proposed method to large and small tumors are compared and summarized. RESULTS: The proposed method is evaluated on 10 liver tumors of various geometric characteristics from 7 cases. The test results show that the average path planning time and average ablation efficiency are 41.4 s and 60.19%, respectively. For tumors of different sizes, the planning results obtained from the proposed method have similar healthy tissue coverage. Through the clinical evaluation of doctors, the planning results meet the needs of RFA for liver tumors. CONCLUSIONS: The proposed method can provide reasonable puncture paths in RFA planning, which is beneficial to ensure the safety and efficiency of liver tumor ablation.

High External Quantum Efficiency Light-Emitting Diodes Enabled by Advanced Heterostructures of Type-II Nanoplatelets.

Colloidal quantum wells (CQWs), also known as nanoplatelets (NPLs), are exciting material systems for numerous photonic applications, including lasers and light-emitting diodes (LEDs). Although many successful type-I NPL-LEDs with high device performance have been demonstrated, type-II NPLs are not fully exploited for LED applications, even with alloyed type-II NPLs with enhanced optical properties. Here, we present the development of CdSe/CdTe/CdSe core/crown/crown (multi-crowned) type-II NPLs and systematic investigation of their optical properties, including their comparison with the traditional core/crown counterparts. Unlike traditional type-II NPLs such as CdSe/CdTe, CdTe/CdSe, and CdSe/CdSexTe1-x core/crown heterostructures, here the proposed advanced heterostructure reaps the benefits of having two type-II transition channels, resulting in a high quantum yield (QY) of 83% and a long fluorescence lifetime of 73.3 ns. These type-II transitions were confirmed experimentally by optical measurements and theoretically using electron and hole wave function modeling. Computational study shows that the multi-crowned NPLs provide a better-distributed hole wave function along the CdTe crown, while the electron wave function is delocalized in the CdSe core and CdSe crown layers. As a proof-of-concept demonstration, NPL-LEDs based on these multi-crowned NPLs were designed and fabricated with a record high external quantum efficiency (EQE) of 7.83% among type-II NPL-LEDs. These findings are expected to induce advanced designs of NPL heterostructures to reach a fascinating level of performance, especially in LEDs and lasers.

SOX7 modulates the progression of hepatoblastoma through the regulation of Wnt/ß-catenin signaling pathway.

Aims: Hepatoblastoma (HB) was reported as the frequently diagnosed primary hepatic malignant tumor among children. No reports have shown the function of SOX7 and its relationship with the Wnt/ß-catenin pathway in HB. Materials and Methods: SOX7 and factors related to Wnt/ß-catenin pathway were detected using reverse transcription-quantitative polymerase chain reaction (RT-PCR) and Western blotting. MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium and flow cytometry were used to detect HB cell proliferation and apoptosis. The transwell assay uses cell invasion. Results: In this study, RT-PCR, Western blotting, and immunohistochemistry results indicated that the expression of SOX7 was significantly reduced in HB tissues compared with adjacent noncancerous tissues, while the ß-catenin was significantly increased in HB tissues compared with adjacent noncancerous tissues. There were significant differences in the PRETEXT stage and tumor metastasis between patients with low expression and high expression of SOX7. Moreover, it was found that the overexpression of SOX7 and inhibiting Wnt/ß-catenin pathway significantly reduced the cell proliferation and invasion, while the cell apoptosis was significantly increased compared with the control group. Conclusions: This study shows that SOX7 was downexpressed in HB tumor tissues. Moreover, ex vivo experiments indicated that SOX7 was related to ß-catenin and regulated the progression of HB cells.

An Individualized Prognostic Signature for Clinically Predicting the Survival of Patients With Bladder Cancer.

Background: The tumor immune microenvironment (TIME) plays an important role in the development and prognosis of bladder cancer. It is essential to conduct a risk model to explore the prognostic value of the immunologic genes and establish an individualized prognostic signature for predicting the survival of patients with bladder cancer. Method: The differentially expressed immunologic genes (DEGs) are identified in The Cancer Genome Atlas (TCGA). The nonnegative matrix factorization (NMF) was used to stratify the DEGs in TCGA. We used the least absolute shrinkage and selection operator (LASSO) Cox regression and univariate Cox analysis to establish a prognostic risk model. A nomogram was used to establish an individualized prognostic signature for predicting survival. The potential pathways underlying the model were explored. Results: A total of 1,018 DEGs were screened. All samples were divided into two clusters (C1 and C2) by NMF with different immune cell infiltration, and the C2 subtype had poor prognosis. We constructed a 15-gene prognostic risk model from TCGA cohort. The patients from the high-risk group had a poor overall survival rate compared with the low-risk group. Time-dependent ROC curves demonstrated good predictive ability of the signature (0.827, 0.802, and 0.812 for 1-, 3-, and 5-year survival, respectively). Univariate and multivariate Cox regression analyses showed that the immunologic prognostic risk model was an independent factor. The decision curve demonstrated a relatively good performance of the risk model and individualized prognostic signature, showing the best net benefit for 1-, 3-, and 5-year OS. Gene aggregation analysis showed that the high-risk group was mainly concentrated in tumorigenesis and migration and immune signaling pathways. Conclusion: We established a risk model and an individualized prognostic signature, and these may be useful biomarkers for prognostic prediction of patients with bladder cancer.

Network Pharmacology and Bioinformatics Analyses Identify Intersection Genes of Vitamin D3 and COVID-19 as Potential Therapeutic Targets.

Purpose: The persistent pandemic of coronavirus disease 2019 (COVID-19), the discovery of gastrointestinal transmission routes and the possible susceptibility of cancer patients to COVID-19 have forced us to search for effective pathways against stomach adenocarcinoma (STAD)/COVID-19. Vitamin D3 (VD3) is a steroid hormone with antiviral, anti-inflammatory and immunomodulatory properties. This study aimed to evaluate the possible functional role and potential mechanisms of action of VD3 as an anti-COVID-19 and anti- STAD. Methods: Clinicopathological analysis, enrichment analysis and protein interaction analysis using bioinformatics and network pharmacology methods. Validate the binding activity of VD3 to core pharmacological targets and viral crystal structures using molecular docking. Results: We revealed the clinical characteristics of STAD/COVID-19 patients. We also demonstrated that VD3 may be anti- STAD/COVID-19 through antiviral, anti-inflammatory, and immunomodulatory pathways. Molecular docking results showed that VD3 binds well to the relevant targets of COVID-19, including the spike RBD/ACE2 complex and main protease (Mpro, also known as 3CLpro). We also identified five core pharmacological targets of VD3 in anti-STAD/COVID-19 and validated the binding activity of VD3 to PAI1 by molecular docking. Conclusion: This study reveals for the first time that VD3 may act on disease target gene SERPINE1 through inflammatory and viral related signaling pathways and biological functions for the therapy of STAD/COVID-19. This may provide a new idea for the use of VD3 in the treatment of STAD/COVID-19.

Prognostic significance and tumor-immune infiltration of mTOR in clear cell renal cell carcinoma.

Mammalian target of rapamycin (mTOR), a serine/threonine kinase involved in cell proliferation, survival, metabolism and immunity, was reportedly activated in various cancers. However, the clinical role of mTOR in renal cell carcinoma (RCC) is controversial. Here we detected the expression and prognosis of total mTOR and phosphorylated mTOR (p-mTOR) in clear cell RCC (ccRCC) patients, and explored the interactions between mTOR and immune infiltrates in ccRCC. The protein level of mTOR and p-mTOR was determined by western blotting (WB), and their expression was evaluated in 145 ccRCC and 13 non-tumor specimens by immunohistochemistry (IHC). The relationship to immune infiltration of mTOR was further investigated using TIMER and TISIDB databases, respectively. WB demonstrated the ratio of p-mTOR to mTOR was higher in ccRCC than adjacent specimens (n = 3), and IHC analysis elucidated that p-mTOR expression was positively correlated with tumor size, stage and metastasis status, and negatively correlated with cancer-specific survival (CSS). In univariate analysis, high grade, large tumor, advanced stage, metastasis, and high p-mTOR expression were recognized as prognostic factors of poorer CSS, and multivariate survival analysis elucidated that tumor stage, p-mTOR and metastasis were of prognostic value for CSS in ccRCC patients. Further TIMER and TISIDB analyses uncovered that mTOR gene expression was significantly associated with numerous immune cells and immunoinhibitors in patients with ccRCC. Collectively, these findings revealed p-mTOR was identified as an independent predictor of poor survival, and mTOR was associated with tumor immune infiltrates in ccRCC patients, which validated mTOR could be implicated in the initiation and progression of ccRCC.

Expression and prognostic significance of fatty acid synthase in clear cell renal cell carcinoma.

Fatty acid synthase (FASN), a key enzyme essential for fatty acid (FA) synthesis, was reportedly implicated in the initiation and progression of various cancers. However, the clinical significance of FASN in renal cell carcinoma (RCC) has not been fully elucidated yet. Here we compare the expression profile and evaluate the prognostic significance of FASN in clear cell RCC (ccRCC) patients. FASN expression was examined in 3 pairs ccRCC and their adjacent nontumor tissues by western blotting (WB) analysis, and its expression was assessed in 145 ccRCC and 13 nontumor tissues by immunohistochemistry (IHC) analysis with tissue microarrays (TMAs). The prognosis of FASN was further investigated in large-scale database using LinkedOmics (n = 537) and The Cancer Protein Atlas (TCPA, n = 445), respectively. WB detected higher FASN expression in ccRCC than normal tissues, then IHC analysis revealed that FASN expression was positively associated with histological grade, pathological stage, tumor size and metastasis status, and negatively associated with cancer-specific survival (CSS). Univariate survival analysis demonstrated that high grade, advanced stage, large tumor, metastasis, and high FASN expression were significantly associated with a shorter CSS, and multivariate analysis revealed tumor grade, stage, metastasis and FASN were identified as independent predictors for CSS in patients with ccRCC. Further LinkedOmics and TCPA analyses confirmed that high FASN expression was correlated with a poorer overall survival (OS) of ccRCC. Collectively, these findings demonstrated FASN could be a poor prognostic factor in ccRCC patients, which indicated that FA synthesis might be implicated in the tumorigenesis and progression of ccRCC.

Prognostic significance of PI3K/AKT/ mTOR signaling pathway members in clear cell renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is a fatal disease, in which the PI3K/AKT/mTOR signaling pathway serves an important role in the tumorigenesis. Previous studies have reported the prognostic significance of PI3K/AKT/mTOR signaling pathway members in RCC; however, there is insufficient evidence to date to confirm this. Thus, the present study aimed to systematically investigate the prognostic roles of multiple PI3K/AKT/mTOR signaling proteins in clear cell RCC (ccRCC) using online large-scale databases. METHODS: The mRNA expression profiles of PI3K/AKT/mTOR signaling pathway proteins PTEN, PIK3CA, PIK3CB, PIK3CD, PIK3CG, AKT1, AKT2, AKT3 and mTOR were investigated using the Gene Expression Profiling Interactive Analysis (GEPIA) and Oncomine databases, and the protein expression levels of PI3K, AKT and mTOR were detected using western blotting (WB) analysis. In addition, the correlation between mRNA or protein expression levels and the prognostic significance was analyzed using the Kaplan-Meier (K-M) plotter (n = 530), the Human Protein Atlas (HPA; n = 528) and The Cancer Protein Atlas (TCPA; n = 445) databases. RESULTS: The GEPIA revealed that the mRNA expression of major PI3K/AKT/mTOR pathway members, including PTEN, PIK3CA, PIK3CB, AKT1, AKT2 and AKT3, were negatively correlated with ccRCC stages (P < 0.05), though most of their mRNA and protein expression levels were notsignificantly different between ccRCC and normal tissues using GEPIA, Oncomine and WB analyses (P < 0.05). Meanwhile, using the K-M plotter and HPA prognostic analysis, it was found that the mRNA expression levels of the majority of the PI3K/AKT/mTOR signaling pathway members, including PTEN, PIK3CA, PIK3CB, PIK3CG, AKT3 and mTOR were positively correlated with overall survival (OS), whereas PIK3CD mRNA expression was negatively correlated with OS (P < 0.05). Furthermore, TCPA prognostic analysis observed that several of the key molecules of the PI3K/AKT/mTOR signaling pathway [PTEN, p-AKT (S473) and p-mTOR (S2448)] were also positively correlated with OS in patients with ccRCC (P < 0.05). In conclusion, the present study suggested that several members of the PI3K/AKT/mTOR signaling pathway, especially PTEN, may be favorable prognostic factors in ccRCC, which indicated that the PI3K/AKT/mTOR signaling pathway may be implicated in ccRCC initiation and progression.