Tumor cells with stemness (stem‐cell) features contribute to initiation and progression of hepatocellular carcinoma (HCC), but involvement of long noncoding RNAs (lncRNAs) remains largely unclear. ...Genome‐wide analyses were applied to identify tumor‐associated lncRNA‐DANCR. DANCR expression level and prognostic values of DANCR were assayed in two HCC cohorts (China and Korea, n = 135 and 223). Artificial modulation of DANCR (down‐ and overexpression) was done to explore the role of DANCR in tumorigenesis and colonization, and tumor‐bearing mice were used to determine therapeutic effects. We found that lncRNA‐DANCR is overexpressed in stem‐like HCC cells, and this can serve as a prognostic biomarker for HCC patients. Experiments showed that DANCR markedly increased stemness features of HCC cells to promote tumorigenesis and intra‐/extrahepatic tumor colonization. Conversely, DANCR knockdown attenuated the stem‐cell properties and in vivo interference with DANCR action led to decreased tumor cell vitality, tumor shrinkage, and improved mouse survival. Additionally, we found that the role of DANCR relied largely on an association with, and regulation of, CTNNB1. Association of DANCR with CTNNB1 blocked the repressing effect of microRNA (miR)−214, miR‐320a, and miR‐199a on CTNNB1. This observation was confirmed in vivo, suggesting a novel mechanism of tumorigenesis involving lncRNAs, messenger RNAs, and microRNAs. Conclusions: These studies reveal a significance and mechanism of DANCR action in increasing stemness features and offer a potential prognostic marker and a therapeutic target for HCC. (Hepatology 2016;63:499–511)
Down‐regulation of microRNA‐26a (miR‐26a) is associated with poor prognosis of hepatocellular carcinoma (HCC), but its functional mechanism in HCC remains unclear. In this study, we investigated the ...roles of miR‐26a in tumor growth and metastasis of HCC and found that miR‐26a was frequently down‐regulated in HCC tissues. Down‐regulation of miR‐26a correlated with HCC recurrence and metastasis. Through gain‐ and loss‐of‐function studies, miR‐26a was demonstrated to significantly inhibit in vitro cell proliferation, migration, and invasion. In addition, miR‐26a induced G1 arrest and promoted apoptosis of HCC cells. Importantly, miR‐26a suppressed in vivo tumor growth and metastasis in nude mice models bearing human HCC. Interleukin‐6 (IL‐6) was identified as a target of miR‐26a. Knockdown of IL‐6 induced effects on HCC cells similar to those induced by miR‐26a. In contrast, IL‐6 treatment abrogated the effects induced by miR‐26a up‐regulation. Moreover, miR‐26a dramatically suppressed expression of signal transducer and activator of transcription 3 (Stat3) target genes, including Bcl‐2, Mcl‐1, cyclin D1, and MMP2. IL‐6 treatment antagonized this effect, while knockdown of IL‐6 by IL‐6 short hairpin RNA (shIL‐6) induced inhibitory effects on the expression of p‐Stat3 and its main target genes, similar to miR‐26a. The messenger RNA and protein levels of IL‐6 inversely correlated with miR‐26a in HCCs. Patients with high miR‐26a or low IL‐6 in HCC tissues had a better prognosis with longer overall survival (OS) and time to recurrence (TTR). In multivariate analysis, miR‐26a, IL‐6, and their combination were demonstrated to be independent prognostic indicators for OS and TTR of HCC patients. Conclusion: miR‐26a could suppress tumor growth and metastasis of HCC through IL‐6‐Stat3 signaling and is a novel prognostic marker and therapeutic target for HCC. (HEPATOLOGY 2013)
In the tumour microenvironment, critical drivers of immune escape include the oncogenic activity of the tumour cell-intrinsic osteopontin (OPN), the expression of programmed death ligand 1 (PD-L1) ...and the expansion of tumour-associated macrophages (TAMs). We investigated the feasibility of targeting these pathways as a therapeutic option in hepatocellular carcinoma (HCC) mouse models.
We analysed the number of tumour-infiltrating immune cells and the inflammatory immune profiles in chemically induced liver tumour isolated from wild-type and
knockout (KO) mice. In vitro cell cocultures were further conducted to investigate the crosstalk between TAMs and HCC cells mediated by OPN, colony stimulating factor-1 (CSF1) and CSF1 receptor (CSF1R). The in vivo efficacy of anti-PD-L1 and CSF1/CSF1R inhibition was evaluated in OPN overexpressing subcutaneous or orthotopic mouse model of HCC.
The numbers of TAMs, as well as the expression levels of M2 macrophage markers and PD-L1 were significantly decreased, but the levels of cytokines produced by T-helper 1 (Th1) cells were upregulated in tumour tissues from OPN KO mice compared with that from the controls. In addition, we observed a positive association between the OPN and PD-L1 expression, and OPN expression and TAM infiltration in tumour tissues from patients with HCC. We further demonstrated that OPN facilitates chemotactic migration, and alternative activation of macrophages, and promotes the PD-L1 expression in HCC via activation of the CSF1-CSF1R pathway in macrophages. Combining anti-PD-L1 and CSF1R inhibition elicited potent antitumour activity and prolonged survival of OPN
tumour-bearing mice. Histological, flow cytometric and ELISA revealed increased CD8
T cell infiltration, reduced TAMs and enhanced Th1/Th2 cytokine balance in multiple mouse models of HCC.
OPN/CSF1/CSF1R axis plays a critical role in the immunosuppressive nature of the HCC microenvironment. Blocking CSF1/CSF1R prevents TAM trafficking and thereby enhances the efficacy of immune checkpoint inhibitors for the treatment of HCC.
The fall armyworm (FAW), Spodoptera frugiperda is one of the most damaging crop pests, and it has become major threat to the food security of many countries. In order to monitor possible invasion of ...this pest into China, a searchlight trap was established in March 2018 in western Yunnan Province, China, where it has served as the “first station” for many pests that have migrated from Myanmar to China. A number of suspected FAW moths were captured and identified by DNA sequencing. The results showed that the FAW moth was first captured on December 11 and formed its first immigration peak in mid-December 2018. DNA detection revealed that the early invading FAW population was the “corn-strain”. The field survey indicated that the pest mainly colonized corn in Pu'er, Dehong and Baoshan areas. Migration trajectory simulation implied that the moths might have mainly come from the eastern area in the mid-latitude region of Myanmar (20–25°N, 94–100°E). This case study confirmed the first immigration of FAW into China, and will be helpful for guiding monitoring and management work to control this pest.
In recent years, long noncoding RNAs (lncRNAs) have been shown to have critical regulatory roles in cancer biology. However, the contributions of lncRNAs to hepatitis B virus (HBV)‐related ...hepatocellular carcinoma (HCC) remain largely unknown. Differentially expressed lncRNAs between HBV‐related HCC and paired peritumoral tissues were identified by microarray and validated using quantitative real‐time polymerase chain reaction. Liver samples from patients with HBV‐related HCC were analyzed for levels of a specific differentially expressed lncRNA High Expression In HCC (termed lncRNA‐HEIH); data were compared with survival data using the Kaplan‐Meier method and compared between groups by the log‐rank test. The effects of lncRNA‐HEIH were assessed by silencing and overexpressing the lncRNA in vitro and in vivo. The expression level of lncRNA‐HEIH in HBV‐related HCC is significantly associated with recurrence and is an independent prognostic factor for survival. We also found that lncRNA‐HEIH plays a key role in G0/G1 arrest, and further demonstrated that lncRNA‐HEIH was associated with enhancer of zeste homolog 2 (EZH2) and that this association was required for the repression of EZH2 target genes. Conclusions: Together, these results indicate that lncRNA‐HEIH is an oncogenic lncRNA that promotes tumor progression and leads us to propose that lncRNAs may serve as key regulatory hubs in HCC progression. (HEPATOLOGY 2011
In this work, a one‐pot solution method for direct synthesis of interconnected ultrafine amorphous NiFe‐layered double hydroxide (NiFe‐LDH) (<5 nm) and nanocarbon using the molecular precursor of ...metal and carbon sources is presented for the first time. During the solvothermal synthesis of NiFe‐LDH, the organic ligand decomposes and transforms to amorphous carbon with graphitic nanodomains by catalytic effect of Fe. The confined growth of both NiFe‐LDH and carbon in one single sheet results in fully integrated amorphous NiFe‐LDH/C nanohybrid, allowing the harness of the high intrinsic activity of NiFe‐LDH due to (i) amorphous and distorted LDH structure, (ii) enhanced active surface area, and (iii) strong coupling between the active phase and carbon. As such, the resultant NiFe‐LDH/C exhibits superior activity and stability. Different from postdeposition or electrostatic self‐assembly process for the formation of LDH/C composite, this method offers one new opportunity to fabricate high‐performance oxygen evolution reaction and possibly other catalysts.
A one‐pot solution method for direct synthesis of interconnected NiFe‐layered double hydroxide (NiFe‐LDH) (<5 nm) and nanocarbon using molecular precursors is presented. The confined growth of NiFe‐LDH and carbon in one single sheet results in fully integrated amorphous NiFe‐LDH/C nanohybrid with superior activity and durability for oxygen evolution reaction.
Abstract Purpose The prevalence of primary open-angle glaucoma (POAG) in China has been reported previously, which was lower than that in the white and black. However, the incidence of POAG in China ...has not been reported. Therefore, a longitudinal study was conducted to determine the 5-year cumulative incidence and predictors of POAG in China Design Population-based cohort study Methods Fifteen hundred and twenty participants (71.3%) of Bai ethnicity were examined and followed for 5 years. Glaucoma was defined based on the International Society of Geographical and Epidemiological Ophthalmology Classification criteria. Multivariable logistic regression models were fitted to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). Results A total of 19 new cases of POAG were detected. The 5-year cumulative incidence of POAG was 1.3% (95% CI, 0.7-1.9). In multivariate analyses, incident POAG was associated baseline variables including increased age (OR, 4.3; 95% CI, 1.4-13.8; P = 0.02; 70 years or older vs. 50-59 years), elevated IOP (OR, 3.5; 95% CI, 2.0-5.9; P < 0.001; per 10 mmHg increase), lower education level (OR, 0.3; 95% CI, 0.1-0.8; P = 0.02; post primary vs. no formal education) and the presence of myopia (OR, 3.4; 95% CI, 1.3-8.6; P < 0.01). Conclusions The average annual incidence of POAG in Bai Chinese was lower than that in populations of African-descent and White. The results are important to elucidate the racial/ethnic difference in POAG incidence and for the clinical management and health resource allocation in China.
A novel six-band dual circular polarization (CP) rectenna for ambient radio frequency (RF) energy harvesting is presented. Due to the nonlinearity and complex input impedance of the rectifying ...circuit, the design of a multiband and/or broadband rectenna is always challenging and its performance can be easily affected by variation in the input power level and load. Therefore, an improved impedance matching technique is introduced, which is aimed to improve the performance of the rectifier with a varying condition. A broadband dual CP receiving antenna is proposed, which has a very wide bandwidth (from 550 to 2.5 GHz) and a compact size. An annular ring structure and a novel feeding technique are employed in order to reduce the size and improve the antenna performance. As a result, the proposed rectenna is the first design that covers six frequency bands, including part of the digital TV and most cellular mobile and WLAN bands in the U.K., while the optimal load range for a constant conversion efficiency is from 10 to 75 kΩ. The measured results show that the maximum harvested dc power of the rectenna in typical outdoor and indoor environments are 26 and 8 μW, respectively; it can therefore be applied to a range of low-power wireless applications.
Impedance matching networks for nonlinear devices such as amplifiers and rectifiers are normally very challenging to design, particularly for broadband and multiband devices. A novel design concept ...for a broadband high-efficiency rectenna without using matching networks is presented in this paper for the first time. An off-center-fed dipole antenna with relatively high input impedance over a wide frequency band is proposed. The antenna impedance can be tuned to the desired value and directly provides a complex conjugate match to the impedance of a rectifier. The received RF power by the antenna can be delivered to the rectifier efficiently without using impedance matching networks; thus, the proposed rectenna is of a simple structure, low cost, and compact size. In addition, the rectenna can work well under different operating conditions and using different types of rectifying diodes. A rectenna has been designed and made based on this concept. The measured results show that the rectenna is of high power conversion efficiency (more than 60%) in two wide bands, which are 0.9-1.1 and 1.8-2.5 GHz, for mobile, Wi-Fi, and ISM bands. Moreover, by using different diodes, the rectenna can maintain its wide bandwidth and high efficiency over a wide range of input power levels (from 0 to 23 dBm) and load values (from 200 to 2000 Ω). It is, therefore, suitable for high-efficiency wireless power transfer or energy harvesting applications. The proposed rectenna is general and simple in structure without the need for a matching network hence is of great significance for many applications.
Background
Tumor mutation burden (TMB), DNA mismatch repair deficiency (dMMR), microsatellite instability (MSI), and PD‐L1 amplification (PD‐L1 AMP) may predict the efficacy of the PD‐1/PD‐L1 ...blockade. With the broadening landscape of immunotherapy use, it is important to identify patients who are likely to benefit from the therapy. This study aimed to characterize the distributions of these biomarkers and explore the relationships among these biomarkers for Chinese patients with cancer.
Methods
In this study, we examined the aforementioned biomarkers in more than 1000 Chinese patients with cancer. These biomarkers were determined based on whole‐exome sequencing (WES) of tumor/blood samples.
Results
Of the 953 samples from Chinese cancer patients assessed in this study, 35% exhibited high TMB (TMB‐H), 4% were positive for high MSI (MSI‐H), dMMR occurred in 0.53%, and PD‐L1 AMP was positive in 3.79%. We found higher rates of TMB‐H among hepatocellular carcinoma, breast cancer, and esophageal cancer patients than was reported for The Cancer Genome Atlas (TCGA) data. Lung cancer patients with EGFR mutations had significantly lower TMB values than those with wild‐type EGFR, and increased TMB was significantly associated with dMMR in colorectal cancer (CRC). The frequency of tumors with MSI‐H was the highest in CRC and gastric cancer. PD‐L1 AMP occurred most frequently in lung squamous cell carcinoma and HER2‐positive breast cancer. While MSI and dMMR are associated with higher mutational loads, correlations between TMB‐H and other biomarkers, between MSI‐H and dMMR, and between PD‐L1 AMP and other biomarkers were low, indicating different underlying causes of the four biomarkers.
Conclusion
The results reveal the frequency of these biomarkers in different malignancies, with potential implications for PD‐1/PD‐L1 blockade use for Chinese patients with cancer.
Our study showed that incidence rates among 953 Chinese cancer patients of TMB‐H, MSI‐H, dMMR, and PD‐L1 AMP were 35%, 4%, 0.53%, and 3.79%, respectively. These findings may provide important information prior to administration of PD‐1/PD‐L1 blockade treatment to Chinese patients with cancer.
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