Re-Recognizing the Cellular Origin of the Primary Epithelial Tumors of the Liver.

The primary epithelial tumors of the liver (PETL) are composed of a series of heterogeneous tumors. Although the classification of PETLs has been updated several times by the World Health Organization, the cellular origins of some tumors in this family remain to be precisely depicted. In addition, certain tumors in different categories have similar histology, molecular phenotypes and biological characteristics, suggesting that they may have the same cellular origin. In this work, a narrative review method was adopted to review the relevant papers. By comparing the expression profiles of biomarkers of liver epithelium at different lineages and stages of differentiation, the cells-of-origin of some major members of the PETL family were reassessed. We propose that 1) hepatic adenomas, hepatocellular carcinomas (HCCs) and pure fetal hepatoblastomas (HBs) share the same spectrum in their cellular origin including the hepatocytic-committed progenitors (HCP) and their differentiated descendants. 2) Bile duct adenomas, peribiliary cysts and intrahepatic cholangiocellular carcinomas (ICCs) can share the same spectrum in their cellular origin including the cholangiocytic-committed progenitors (CCP) and their differentiated descendants. 3) The cells-of-origin of embryonal HBs include liver stem cells (LSCs), hepatoblasts, and transitional cells between them. Embryonal HB with small cell element, small cell undifferentiated HB and small cell neuroendocrine carcinoma of the liver can have the same or similar cells-of-origin from LSC. Embryonal HB lacking the small cell component of the LSC phenotype and presenting both hepatocytic and bile duct/ductule components may originate from actual hepatoblasts/hepatic progenitor cells (HPCs) as the combined HCC-ICC does. 4) Teratoid hepatoblastoma and mixed epithelial/mesenchymal HBs can be derived from the LSCs or even less committed extrahepatic pluripotent stem cell. 5) Many members of the PETLs family, including those derived from LSCs, hepatoblasts/HPCs, early HCPs and CCPs, have neuroendocrine potentiality. Except for those primary hepatic neuroendocrine tumor (PHNET) exhibit hepatocytic and/or cholangiocytic phenotypes, other PHNETs subtype may be derived from the descendants of LSC that differentiate towards the upper digestive tract, pancreas or other lineages.

Microarray Identifies a Key Carcinogenic Circular RNA 0008594 That Is Related to Non-Small-Cell Lung Cancer Development and Lymph Node Metastasis and Promotes NSCLC Progression by Regulating the miR-760-Mediated PI3K/AKT and MEK/ERK Pathways.

PURPOSE: This study aimed to explore the circular RNA (circRNA/circ) profile engaged in non-small cell lung cancer (NSCLC) development and metastasis and to investigate potentially key carcinogenic circRNAs related to NSCLC. METHODS: CircRNA profiles between 10 NSCLC tissues and 10 adjacent tissues and between five NSCLC tissues with lymph node metastasis (LNM) and five NSCLC tissues without LNM were detected by Arraystar Human circRNA Array followed by bioinformatics. Circ_0008594 knockdown, circ_0004293 overexpression, and circ_0003832 overexpression plasmids were transfected into H23 and H460 cells to sort potential oncogenic circRNA. Then circ_0008594 overexpression and knockdown plasmids were transfected, followed by that circ_0008594 knockdown plus miR-760 knockdown plasmids were transfected into these cells. Cell proliferation, apoptosis, invasion, stemness, and pathways were detected. In addition, xenograft mice models were constructed via injecting H23 cells with circ_0008594 overexpression or knockdown to validate the findings. RESULTS: A total of 455 dysregulated circRNAs in NSCLC tissues versus adjacent tissues and 353 dysregulated circRNAs in NSCLC tissues with LNM versus those without LNM were discovered. Via cross-analysis, 19 accordant circRNAs were uncovered, among which three candidate circRNAs (circ_0008594, circ_0004293, circ_0003832) were chosen for functional experiments, during which it was observed that circ_0008549 affected H23 and H460 cell proliferation and apoptosis more obviously than circ_0004293 and circ_0003832. Subsequent experiments showed that circ_0008594 promoted H23 and H460 cell proliferation and invasion but affected stemness less and negatively regulated miR-760 via direct binding. Furthermore, miR-760 attenuated the effect of circ_0008549 on regulating H23 and H460 cell functions and the PI3K/AKT and MEK/ERK pathways. In vivo experiments further confirmed that circ_0008549 increased tumor volume, epithelial-mesenchymal transition, and the PI3K/AKT and MEK/ERK pathways while reducing tumor apoptosis and miR-760 NSCLC xenograft models. CONCLUSION: Our study identifies several valuable circRNAs related to NSCLC development and LNM. Furthermore, as a key functional circRNA, circ_0008594 was observed to promote NSCLC progression by regulating the miR-760-mediated PI3K/AKT and MEK/ERK pathways.

Prediction of Early Recurrence of Solitary Hepatocellular Carcinoma after Orthotopic Liver Transplantation.

Hepatocellular carcinomas(HCC) consisted of heterogeneous subtypes with different recurrence probabilities after liver transplantation(LT). Our study aimed to develop an improved model for predicting the recurrence of solitary HCC after LT. In this retrospective study, 151 solitary HCC patients who received orthotopic LT over a period of 10 consecutive years were included. All recipients received graft from deceased donors. The first eligible 50 patients were used as validation cohort and others were utilized to construct the model. A two-tailed P < 0.05 was considered to indicate statistical significance for all analysis. Based on the maximisation of the Youden's index, the optimal cutoff values for alpha-fetoprotein(AFP) and tumor diameter were 261.6 ng/mL and 3.6 cm, respectively. Vascular involvement includes gross and microscopic vascular invasion. Variables potentially affecting recurrence-free survival(RFS) were examined using univariate and multivariate Cox regression analysis. Univariate and multivariate analysis revealed that AFP, tumor diameter, vascular invasion and cytokeratin-19/glypican-3 sub-typing were independent prognostic factors for RFS, thus comprised the risk scoring model. The AUC values of the model in the cohorts were significantly higher than that of the Milan, UCSF, Fudan and Hangzhou criteria. These findings suggest the model has high performance in predicting early recurrence of solitary HCC patients after LT.

Transcription Factor p53 Suppresses Tumor Growth by Prompting Pyroptosis in Non-Small-Cell Lung Cancer.

OBJECTIVE: To evaluate the effect of p53 on pyroptosis and its inhibitory role on tumor growth in non-small-cell lung cancer (NSCLC). METHODS: The correlation of p53 and pyroptosis was determined in tumor tissues of NSCLC patients. The pyroptotic level was detected in A549 cells to clarify the effect of p53 on pyroptosis. p53 overexpression A549 tumor-bearing mice were used to clarify the therapeutic target of p53 in NSCLC treatment. RESULTS: p53 expression level was positively related to pyroptosis in NSCLC tissues. In in vitro assays, p53 directly regulated pyroptosis in A549 cells. p53-specific knockdown blocked lipopolysaccharide- (LPS-) induced pyroptosis. In in vivo assays, p53 overexpression in A549 markedly decreased tumor growth and death rate by increasing the pyroptotic level. CONCLUSIONS: Upregulation of p53 prompts pyroptosis to produce anti-NSCLC effects suggesting the potential of p53 on suppressing tumor growth in NSCLC patients.

Histopathological characteristics of needle core biopsy and surgical specimens from patients with solitary hepatocellular carcinoma or intrahepatic cholangiocarcinoma.

BACKGROUND: Pathological manifestations of hepatic tumours are often associated with prognosis. Although surgical specimens (SS) can provide more information, currently, pre-treatment needle core biopsy (NCB) is increasingly showing important value in understanding the nature of liver tumors and even in diagnosis and treatment decisions. However, the concordance of the clinicopathological characteristics and immunohistochemical (IHC) staining between NCB and SS from patients with hepatic tumours were less concerned. AIM: To introduce a more accurate method for interpreting the IHC staining results in order to improve the diagnostic value of hepatic malignancy in NCB samples. METHOD: A total of 208 patients who underwent both preoperative NCB and surgical resection for hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC) between 2008 and 2015 were enrolled in this study. The expression of CK19, GPC3, and HepPar1 were detected by IHC staining. Clinicopathological, NCB, and surgical data were collected and analysed using χ 2 and kappa statistics. RESULTS: Morphologically, the presence of compact tumour nests or a cord-like structure in NCB was considered the primary cause of misdiagnosis of HCC from ICC. The kappa statistic showed a moderate agreement in histomorphology (k = 0.504) and histological grade (k = 0.488) between NCB and SS of the tumours. A 4-tier (+++, ++, +, and -) scoring scheme that emphasized the focal neoplastic cell immunoreactivity of tumour cells revealed perfect concordance of CK19, GPC3 and HepPar1 between NCB and SS (k = 0.717; k = 0.768; k = 0.633). Furthermore, with the aid of a binary classification derived from the 4-tier score, a high concordance was achieved in interpreting the IHC staining of the three markers between NCB and final SS (k = 0.931; k = 0.907; k = 0.803), increasing the accuracy of NCB diagnosis C (k = 0.987; area under the curve = 0.997, 95%CI: 0.990-1.000; P < 0.001). CONCLUSION: These findings imply that reasonable interpretation of IHC results in NCB is vital for improving the accuracy of tumour diagnosis. The simplified binary classification provides an easy and applicable approach.

Double-Dose Adenovirus-Mediated Adjuvant Gene Therapy Improves Liver Transplantation Outcomes in Patients with Advanced Hepatocellular Carcinoma.

The present clinical trial assessed the effect of double-dose administration of replication-deficient adenovirus-thymidine kinase and ganciclovir (ADV-TK/GCV) in patients with advanced hepatocellular carcinoma (HCC) who underwent liver transplantation (LT). Eighty-six patients with single tumor diameters >5 cm or multiple tumors with diameters >3 cm each, regardless of vascular invasion, were examined over a follow-up period of 61 months. All patients underwent orthotopic LT; 43 received LT only, and 43 received LT plus double-dose ADV-TK/GCV gene therapy (LT + ADV-TK/GCV). Recurrence-free survival (RFS) and overall survival (OS) rates, as well as therapeutic safety, were assessed. The RFS and OS rates in LT + ADV-TK/GCV patients at 3 years (55.9% and 60.3%, respectively) were significantly higher than those in the LT-only group (13.5% and 19.3%, respectively; p < 0.001). LT + ADV-TK/GCV patients without vascular invasion showed significant improvement in RFS (73.7%) and OS (68.6%). LT + ADV-TK/GCV patients without extrahepatic vascular invasion experienced higher OS versus LT-only patients. Double-dose ADV-TK/GCV gene therapy combined with LT was safe and improved RFS and OS in advanced HCC patients without vascular invasion over the 5-year follow-up period. The potential to select patients with intrahepatic and extrahepatic vascular invasion for LT requires further confirmation.

Prediction of early recurrence of hepatocellular carcinoma within the Milan criteria after radical resection.

Approximately 50% hepatocellular carcinoma patients meeting the Milan criteria utilized to develop an improved prognostic model for predicting the recurrence in these patients. Using univariate and multivariate analysis, cytokeratin-19 and glypican-3 expression patterns, tumor number and histological grading from eight putative prognostic factors comprised the risk factor scoring model to predict the tumor recurrence. In the training cohort, the area under roc curve (AUC) value of the model was 0.715 [95% confidence interval (CI) = 0.645-0.786, P<0.001], which was the highest among all the parameters. The performance of the model was assessed using an independent validation cohort, wherein the AUC value was 0.760 (95% CI=0.647-0.874, P<0.001), which was higher than the other factors. The results indicated that model had high performance with adequate discrimination ability. Moreover, it significantly improved the predictive capacity for the recurrence in patients with hepatocellular carcinoma within the Milan criteria after radical resection.

Achieving 12-bit perceptual quantizer curve with liquid crystal display.

We proposed a scheme to drive the light emitting diode (LED) backlight and liquid crystal (LC) panel simultaneously to achieve 10,000-nit 12-bit perceptual quantizer (PQ) curve, which is required by high dynamic range (HDR) displays. Besides the relative fast response time and low driving voltage, this approach can also mitigate image noises.

Simple Risk Score for Prediction of Early Recurrence of Hepatocellular Carcinoma within the Milan Criteria after Orthotopic Liver Transplantation.

Ten to twenty percent of the hepatocellular carcinoma (HCC) patients fulfilling the Milan criteria (MC) recurred within three years after orthotopic liver transplantation (OLT). We therefore utilize a training cohort to develop an improved prognostic model for predicting the recurrence in these patients. By univariate and multivariate analysis, AFP level [cut-off value: 321 ng/mL, area under the curve (AUC) = 0.724, 95% confidence interval (CI) = 0.604-0.843, P < 0.001] and cytokeratin-19 (CK19) and glypican-3 (GPC3) expression pattern from nine putative prognostic factors were entered in risk factor scoring model to conjecture the tumor recurrence. In the training cohort, the AUC value of the model was 0.767 (95% CI = 0.645-0.890, P < 0.001), which was the highest among all the elements. The model's performance was then assessed using a validation cohort. In the validation cohort, the AUC value of the model was 0.843 (95% CI = 0.720-0.966, P < 0.001) which was higher than any other elements. The results indicated that model had high performance with good discrimination ability and significantly improved the predictive capacity for the recurrence of HCC patients within MC after OLT.

Enlarging the color gamut of liquid crystal displays with a functional reflective polarizer.

We propose to add a functional reflective polarizer (FRP) in the backlight unit to suppress the crosstalk between red, green and blue color filters of a liquid crystal display (LCD) panel. When incorporated with a commercial two-phosphor-converted white light-emitting diode (2pc-WLED), the color gamut of the LCD can be improved from 92% to 115% NTSC standard, which is comparable to the cadmium-based quantum dot (QD) backlight. If a narrow-band color filter is employed, the color gamut can be further enhanced to 135% NTSC. Our design offers an alternative approach to QDs, while keeping low cost and long lifetime. Such a simple yet efficient approach would find widespread applications for enlarging the color gamut of LCDs.

Pixel-by-pixel local dimming for high-dynamic-range liquid crystal displays.

We propose a high dynamic range (HDR) liquid crystal display (LCD) with pixel-level local dimming. The device structure consists of a pixelated LCD dimming panel to control the backlight intensity entering the master LCD panel. According to our analysis and test cell experiment, this dual-panel display system possesses exceedingly high contrast ratio (> 1,000,000:1) and high bit-depth (> 14 bits) at merely 5 volts. Meanwhile, to mitigate the Moiré effect induced by the cascaded thin-film transistor (TFT) backplanes, we separate the two LCD panels with a polarization-dependent scattering film. The pros and cons of this HDR display are discussed.

Going beyond the limit of an LCD's color gamut.

In this study, we analyze how a backlight's peak wavelength, full-width at half-maximum (FWHM), and color filters affect the color gamut of a liquid crystal display (LCD) device and establish a theoretical limit, even if the FWHM approaches 1 nm. To overcome this limit, we propose a new backlight system incorporating a functional reflective polarizer and a patterned half-wave plate to decouple the polarization states of the blue light and the green/red lights. As a result, the crosstalk between three primary colors is greatly suppressed, and the color gamut is significantly widened. In the experiment, we prepare a white-light source using a blue light-emitting diode (LED) to pump green perovskite polymer film and red quantum dots and demonstrate an exceedingly large color gamut (95.8% Rec. 2020 in Commission internationale de l'éclairage (CIE) 1931 color space and 97.3% Rec. 2020 in CIE 1976 color space) with commercial high-efficiency color filters. These results are beyond the color gamut limit achievable by a conventional LCD. Our design works equally well for other light sources, such as a 2-phosphor-converted white LED.

Ultrastable, Highly Luminescent Organic-Inorganic Perovskite-Polymer Composite Films.

A simple yet general swelling-deswelling microencapsulation strategy has been developed to achieve well dispersed and intimately passivated crystalline organic-inorganic perovskites nanoparticles within polymer matrixes and results in a series of highly luminescent CH3 NH3 PbBr3 (MAPbBr3 )-polymer composite films with unprecedented water and thermal stabilities and superior color purity.

Correlated color temperature tunable white LED with a dynamic color filter.

We proposed a new device structure to dynamically tune the correlated color temperature (CCT) of a white light-emitting-diode (WLED). The key component is a dynamic color filter, consisting of a liquid crystal (LC) cell sandwiched between two cholesteric LC films whose Bragg reflection band covers the blue wavelength of the WLED. When a voltage is applied to the LC cell, the transmittance of blue light is changed, while the longer wavelength part remains unaffected, resulting in a tunable CCT. Validated by experiment, our design exhibits several advantages, such as reasonably wide tuning range (6916K to 3253K), low operation voltage (~3.2 V), simple device configuration, and low cost. It is a strong contender for next generation smart lighting.

CK19 and Glypican 3 Expression Profiling in the Prognostic Indication for Patients with HCC after Surgical Resection.

This retrospective study was designed to investigate the correlation between a novel immunosubtyping method for hepatocellular carcinoma (HCC) and biological behavior of tumor cells. A series of 346 patients, who received hepatectomy at two surgical centers from January 2007 to October 2010, were enrolled in this study. The expressions of cytokeratin 19 (CK19), glypican 3 (GPC3), and CD34 were detected by immunohistochemical staining. The clinical stage was assessed using the sixth edition tumor-node-metastasis (TNM) system (UICC/AJCC, 2010).Vascular invasion comprised both microscopic and macroscopic invasion. The tumor size, lymph node involvement, and metastasis were determined by pathological as well as imaging studies. Recurrence was defined as the appearance of new lesions with radiological features typical of HCC, seen by at least two imaging methods. Survival curves for the patients were plotted using the Kaplan-Meier method, and differences between the curves were assessed using the log-rank test. Significant differences in morphology, histological grading, and TNM staging were observed between groups. Based on the immunohistochemical staining, the enrolled cases were divided into CK19+/GPC3+, CK19-/GPC3+ and CK19-/GPC3- three subtypes. CK19+/GPC3+ HCC has the highest risk of multifocality, microvascular invasion, regional lymph node involvement, and distant metastasis, followed by CK19-/GPC3+ HCC, then CK19-/GPC3-HCC. CK19+/GPC3+ HCC has the shortest recurrence time compared to other immunophenotype HCCs. CK19 and GPC3 expression profiling is an independent prognostic indicator in patients with HCC, and a larger sample size is needed to further investigate the effect of this immunosubtyping model in stratifying the outcome of HCC patients.

Polarizing grating color filters with large acceptance angle and high transmittance.

We design and simulate a polarizing color filter with a sub-wavelength metal-dielectric grating. It manifests several advantages: a large acceptance angle (up to ±50°), high transmittance (74.3%-92.7%), low absorption loss (∼3.3%), and a high extinction ratio. This polarizing color filter can be integrated into a liquid-crystal display (LCD) backlight system to simultaneously recycle the light according to its color and polarization. In combination with a specially designed directional backlight, this newly proposed LCD system can theoretically improve optical efficiency up to ∼2.5×, and also provides a large ambient contrast ratio and a wide view. Our approach enables an ultra-low-power LCD without using the complicated field-sequential-color technique.

Functional reflective polarizer for augmented reality and color vision deficiency.

We report a functional reflective polarizer that can be incorporated into a compact augmented reality system. The design principle of the functional reflective polarizer is explained and two design examples are illustrated. In the first example, with the specially designed functional reflective polarizer, the transmittance of the augment reality system is relatively high as compared to a polarizing beam splitter or a conventional reflective polarizer. Such a functional reflective polarizer can also be used for vehicular displays. For the second example, the functional reflective polarizer is specially tailored to help those people with color vision deficiency.

Freeform reflectors for architectural lighting.

We propose an improved method to design freeform reflectors for architectural lighting: one for accent lighting and another for large area wall washing. The designed freeform reflectors effectively distribute light fluxes over the target surfaces, and generate appropriate illumination patterns for comfortable visual environments, which provides greater flexibility for lighting designs, allows many challenging designs, and improves energy-efficiency simultaneously.

Realizing Rec. 2020 color gamut with quantum dot displays.

We analyze how to realize Rec. 2020 wide color gamut with quantum dots. For photoluminescence, our simulation indicates that we are able to achieve over 97% of the Rec. 2020 standard with quantum dots by optimizing the emission spectra and redesigning the color filters. For electroluminescence, by optimizing the emission spectra of quantum dots is adequate to render over 97% of the Rec. 2020 standard. We also analyze the efficiency and angular performance of these devices, and then compare results with LCDs using green and red phosphors-based LED backlight. Our results indicate that quantum dot display is an outstanding candidate for achieving wide color gamut and high optical efficiency.

Enhancing the outcoupling efficiency of quantum dot LEDs with internal nano-scattering pattern.

We report an effective method to extract light from quantum-dot light emitting diodes (QLEDs) by embedding an internal nano-scattering pattern structure. We use finite-difference time-domain method to analyze the light extraction efficiency of red QLEDs with periodic, quasi-random, and random internal nano-scattering pattern structures. Our simulation results indicate that random internal nano-scattering pattern can greatly enhance the outcoupling efficiency while keeping wide viewing angle for the red QLED. Similar results are obtained by extending this approach to green and blue QLEDs. With the proposed red, green, and blue QLEDs combination, we achieve 105.1% Rec. 2020 color gamut in CIE 1976 color space. We demonstrate that internal nano-scattering pattern structures are attractive for display applications, especially for enhancing the outcoupling efficiency of blue QLEDs.