Malus’ law regulating the intensity of light when passed through a polarizer, forms the solid basis for image steganography based on orthogonal polarizations of light to convey hidden information ...without adverse perceptions, which underpins important practices in information encryptions, anti‐counterfeitings, and security labels. Unfortunately, the restriction to orthogonal states being taken for granted in the common perceptions fails to advance cryptoinformation to upgraded levels of security. By introducing a vectorial compound metapixel design, arbitrary nonorthogonal polarization multiplexing of independent grayscale images with high fidelity and strong concealment is demonstrated. The Jones matrix treatment of compound metapixels consisting of double atoms with tailored in‐plane orientation sum and difference allows point‐by‐point configuring of both the amplitude and polarization rotations of the output beam in an analytical and linear form. With this, both multiplexing two continuous grayscale images in arbitrary nonorthogonal polarization angles and concealing grayscale image on another in an arbitrary disclosure angle window are experimentally demonstrated in the visible TiO2 metasurface platform. The methods shed new light on multifarious metaoptics by harnessing the new degree of freedom and unlock the full potential of metasurface polarization optics.
A vectorial compound metapixel design enables independent and linear modulations of the output beam in both amplitude and polarization rotations across the Malus metasurface. With this, arbitrary‐angle steganography is demonstrated by both multiplexing two continuous grayscale images in arbitrary nonorthogonal polarization angles and concealing one grayscale image on another in an arbitrary disclosure angle window.
Background and Aims
There is growing evidence that single‐stranded, circular RNA (circRNA) plays a key role in the development of certain cancers, including hepatocellular carcinoma (HCC). It is less ...clear, however, what role circRNA plays in HCC metastasis.
Approach and Results
In this study, through circRNA sequencing, we identified a circRNA: circASAP1 (a circRNA derived from exons 2 and 3 of the ASAP1 gene, hsa_circ_0085616), which is associated with pulmonary metastasis after curative resection in patients with HCC. CircASAP1 was overexpressed in HCC cell lines with high metastatic potential and in metastatic HCCs. In vitro, circASAP1 promoted cell proliferation, colony formation, migration, and invasion, and in vivo, it enhanced tumor growth and pulmonary metastasis. Mechanism studies showed that circASAP1 acts as a competing endogenous RNA for microRNA 326 (miR‐326) and microRNA 532‐5p (miR‐532‐5p), both of which are tumor suppressors in HCC. We found that mitogen‐activated protein kinase (MAPK) 1 and colony stimulating factor (CSF)‐1 were direct common targets for microRNA 326 (miR‐326) and microRNA 532‐5p (miR‐532‐5p), which were regulated by circASAP1. CircASAP1 promotes HCC cell proliferation and invasion by regulating miR‐326/miR‐532‐5p‐MAPK1 signaling and, furthermore, mediates tumor‐associated macrophage infiltration by regulating the miR‐326/miR‐532‐5p‐CSF‐1 pathway. Clinical HCC samples exhibited a positive correlation between circASAP1 expression and levels of CSF‐1, MAPK1, and CD68+ tumor‐associated macrophages, all of which were predictive of patient outcomes.
Conclusion
We identified circASAP1 as a key regulator of HCC metastasis that acts on miR‐326/miR‐532‐5p‐MAPK1/CSF‐1 signaling and serves as a prognostic predictor in patients with HCC.
MicroRNAs (miRNAs) play a critical role in regulation of tumor metastasis. However, the role of these molecules in hepatocellular carcinoma (HCC) has not been fully elucidated. In this study, we ...employed miRNA‐sequencing and identified 22 miRNAs involved in HCC metastasis. One of these, miR‐28‐5p, was down‐regulated in HCCs. This down‐regulation correlated with tumor metastasis, recurrence, and poor survival. Biofunctional investigations revealed that miR‐28‐5p deficiency promoted tumor growth and metastasis in nude mice without altering the in vitro biological characteristics of HCC cells. Through gene expression profiles and bioinformatics analysis, we identified interleukin‐34 (IL‐34) as a direct target of miR‐28‐5p, and the effects of miR‐28‐5p deficiency on HCC growth and metastasis was dependent on IL‐34‐mediated tumor‐associated macrophage (TAM) infiltration. Moreover, we found that TAMs induced by miR‐28‐5p‐IL‐34 signaling inhibit miR‐28‐5p expression on HCC cells by transforming growth factor beta 1, resulting in an miR‐28‐5p‐IL‐34‐macrophage‐positive feedback loop. In clinical HCC samples, miR‐28‐5p levels were inversely correlated with IL‐34 expression and the number of TAMs. Patients with low miR‐28‐5p expression, high IL‐34 levels, and high numbers of TAMs had a poor prognosis with shorter overall survival and time to recurrence. Conclusion: A miR‐28‐5p‐IL‐34‐macrophage feedback loop modulates HCC metastasis and serves as a novel prognostic factor as well as a therapeutic target for HCC. (Hepatology 2016;63:1560‐1575)
Tumor‐associated neutrophils (TANs) play a crucial role in tumor development and progression in the cancer microenvironment. Despite increased understanding of TAN contributions to hepatocellular ...carcinoma (HCC) progression and prognosis, the direct interaction between TANs and HCC cells is not fully understood. In this study, we tested the effect of TANs on HCC cells in vitro and in vivo and investigated the mechanism of interaction between them. Our results showed that TANs secreted bone morphogenetic protein 2 and transforming growth factor beta 2 and triggered microRNA 301b‐3p (miR‐301‐3p) expression in HCC cells, subsequently suppressed gene expression of limbic system–associated membrane protein (LSAMP) and CYLD lysine 63 deubiquitinase (CYLD), and increased stem cell characteristics in HCC cells. These TAN‐induced HCC stem‐like cells were hyperactive in nuclear factor kappa B signaling, secreted higher levels of chemokine (C‐X‐C motif) ligand 5 (CXCL5), and recruited more TAN infiltration, suggesting a positive feedback loop. In clinical HCC samples, increased TANs correlated with elevated miR‐301b‐3p, decreased LSAMP and CYLD expression, and increased nuclear p65 accumulation and CXCL5 expression, all of which predicted patient outcome. Conclusion: Our work identified a positive feedback loop governing cancer stem‐like cells and TANs in HCC that controls tumor progression and patient outcome.
Cross-species transmission of viruses from wildlife animal reservoirs poses a marked threat to human and animal health
. Bats have been recognized as one of the most important reservoirs for emerging ...viruses and the transmission of a coronavirus that originated in bats to humans via intermediate hosts was responsible for the high-impact emerging zoonosis, severe acute respiratory syndrome (SARS)
. Here we provide virological, epidemiological, evolutionary and experimental evidence that a novel HKU2-related bat coronavirus, swine acute diarrhoea syndrome coronavirus (SADS-CoV), is the aetiological agent that was responsible for a large-scale outbreak of fatal disease in pigs in China that has caused the death of 24,693 piglets across four farms. Notably, the outbreak began in Guangdong province in the vicinity of the origin of the SARS pandemic. Furthermore, we identified SADS-related CoVs with 96-98% sequence identity in 9.8% (58 out of 591) of anal swabs collected from bats in Guangdong province during 2013-2016, predominantly in horseshoe bats (Rhinolophus spp.) that are known reservoirs of SARS-related CoVs. We found that there were striking similarities between the SADS and SARS outbreaks in geographical, temporal, ecological and aetiological settings. This study highlights the importance of identifying coronavirus diversity and distribution in bats to mitigate future outbreaks that could threaten livestock, public health and economic growth.
A (poly) piperazine pyrophosphate (PIPP) was synthesized and its chemical structure was confirmed via Fourier transform infrared spectroscopy, 1H nuclear magnetic resonance, and 31P nuclear magnetic ...resonance. PIPP was used together with melamine polyphosphate (MPP) as an ammonium polyphosphate (APP)‐free intumescent flame retardant (IFR) to prepare several flame‐retardant polypropylene (FRPP) composites. The flame retardancy and burning behaviors of the composites were investigated via limiting oxygen index (LOI) determination, vertical burning tests (UL‐94), and cone calorimeter tests. The thermal properties were investigated by means of thermogravimetric analysis under nitrogen and air atmosphere. Use of PIPP and MPP together yielded an increase in the LOI value, a UL‐94 V‐0 rating, and a decrease in both the values of PHRR and THR in cone calorimetric analysis. Visual observations and scanning electronic microscopy confirmed the occurrence of char formation, which acted as a heat and fire barrier in the condense phase.
•Different types of middle cerebral artery stenosis are identified by HRMRI.•The differences between MMD and intracranial atherosclerotic stenosis are elucidated by HRMRI.•Outer diameter and wall ...thickness of the MCAs in different MRA stages are compared.•The possible mechanism of arterial progressive stenosis in MMD is analyzed.
High resolution magnetic resonance imaging (HRMRI) has been developed as an emerging tool for evaluating intracranial arterial disease. We aimed to analyze the progression of diseased arterial walls in moyamoya disease (MMD) and further elucidate differences compared to intracranial atherosclerotic stenosis using HRMRI. The population of this HRMRI study consisted of 21 patients with MMD and 44 patients with atherosclerotic middle cerebral artery (MCA) stenosis. The cross-sectional images of the MCA wall on HRMRI were compared between the two groups based on outer diameter, wall thickness, luminal stenotic morphology, signal intensity, collateral vascular structures adjacent to stenotic position. In addition, stage classification based on MRA finding was used to depict the course of moyamoya disease. We compared outer diameter and wall thickness of the MCAs in different MRA stages. As a result, the outer diameter and wall thickness of MCAs were significantly smaller in the MMD group than in the atherosclerosis group (outer diameter: MMD 2.01±0.31mm vs. atherosclerosis 3.31±0.37mm, p<0.001 and wall thickness: MMD 0.39±0.19mm vs. atherosclerosis 1.64±0.38mm, p<0.001). The concentric stenosis (91.4% in MMD vs. 36.9% in atherosclerosis group, p<0.001), homogeneous signal intensity (85.7% in MMD vs. 32.6% in atherosclerosis group, p<0.001) and collateral vascular structures (54.3% in MMD vs. 8.7% in atherosclerosis group, p<0.001) were more common in MMD patients. In addition, the outer diameter of MCAs in MMD was significantly different between MRA stage 1 and MRA stage 3 or 4 (MRA stage 1 vs. MRA stage 3, Nemenyi test p=0.005 and MRA stage 1 vs. MRA stage 4, Nemenyi test p=0.009). But the wall thickness of MCAs was no significantly different in different MRA stages (Kruskal–wallis H test, p=0.074). We conclude that HRMRI may be used to identify different types of middle cerebral artery stenosis. MMD was characterized by concentric stenosis, homogeneous signal intensity, and collateral vascular structures in the affected MCA segments by HRMRI. Pathological shrinkage of MCA was an important phenomenon in MMD progression.
Since the endosymbiont origin from α‐Proteobacteria, mitochondrial genomes have undergone extremely divergent evolutionary trajectories among eukaryotic lineages. Compared with the relatively compact ...and conserved animal mitochondrial genomes, plant mitochondrial genomes have many unique features, especially their large and complex genomic arrangements. The sizes of fully sequenced plant mitochondrial genomes span over a 100‐fold range from 66 kb in Viscum scurruloideum to 11 000 kb in Silene conica. In addition to the typical circular structure, some species of plants also possess linear, and even multichromosomal, architectures. In contrast with the thousands of fully sequenced animal mitochondrial genomes and plant plastid genomes, only around 200 fully sequenced land plant mitochondrial genomes have been published, with many being only draft assemblies. In this review, we summarize some of the known novel characteristics found in plant mitochondrial genomes, with special emphasis on multichromosomal structures described in recent publications. Finally, we discuss the future prospects for studying the inheritance patterns of multichromosomal plant mitochondria and examining architectural variation at different levels of taxonomic organization—including at the population level.
A simplified schematic diagram from an insect (A) and plant species (B) with multichromosomal mt genomes.
Background and Aims
Heparin‐binding epidermal growth factor (HB‐EGF), a member of the epidermal growth factor family, plays a pivotal role in the progression of several malignancies, but its role and ...regulatory mechanisms in hepatocellular carcinoma (HCC) remain obscure. Here, we report that transmembrane protease serine 4 (TMPRSS4) significantly enhanced the expression and proteolytic cleavage of HB‐EGF to promote angiogenesis and HCC progression.
Approach and Results
A mechanistic analysis revealed that TMPRSS4 not only increased the transcriptional and translational levels of HB‐EGF precursor, but also promoted its proteolytic cleavage by enhancing matrix metallopeptidase 9 expression through the EGF receptor/Akt/mammalian target of rapamycin/ hypoxia‐inducible factor 1 α signaling pathway. In addition, HB‐EGF promoted HCC proliferation and invasion by the EGF receptor/phosphoinositide 3‐kinase/Akt signaling pathway. The level of HB‐EGF in clinical samples of serum or HCC tissues from patients with HCC was positively correlated with the expression of TMPRSS4 and the microvessel density, and was identified as a prognostic factor for overall survival and recurrence‐free survival, which suggests that HB‐EGF can serve as a potential therapeutic target for HCC. More importantly, we provide a demonstration that treatment with the HB‐EGF inhibitor cross‐reacting material 197 alone or in combination with sorafenib can significantly suppress angiogenesis and HCC progression.
Conclusions
HB‐EGF can be regulated by TMPRSS4 to promote HCC proliferation, invasion, and angiogenesis, and the combination of the HB‐EGF inhibitor cross‐reacting material 197 with sorafenib might be used for individualized treatment of HCC.
Background & Aims Neutrophils can either promote or inhibit tumor progression, depending on the tumor microenvironment, via release of cytokines. Neither the factors produced by tumor-associated ...neutrophils (TANs) nor their effects on tumor progression have been characterized. We investigated the roles of TANs in progression of hepatocellular carcinoma (HCC) using cell lines and immune cells isolated from patients. Methods We performed studies with HepG2, PLC/PRF/5, MHCC97H, and HCCLM3 human and Hepa1-6 and H22 mouse HCC cell lines; expression of chemokines and cytokines were knocked down with small hairpin RNAs. Cells were analyzed in chemotaxis assays and as growth as tumors in mice. HCC tissues and peripheral blood were collected from 20 patients undergoing curative resection or 20 healthy individuals (controls) in 2012 at Zhongshan Hospital in China. TANs and peripheral blood neutrophils (PBNs) were isolated and exposed to conditioned media from HCC cell lines; reverse-transcription polymerase chain reaction was used to quantify the expression of cytokines and chemokines. We collected neutrophils from another 60 patients undergoing curative resection for HCC in 2012 to measure the production of CCL2 and CCL17. Patients were followed up until March 15, 2014. For immunohistochemical analyses, we collected HCC tissues and paired, adjacent, nontumor cirrhotic liver tissues from 832 HCC patients undergoing curative resection from 2006 through 2008. All patients were followed up until March 15, 2013. To study the effects of sorafenib, we collected clinical and pathology data from 46 patients who underwent curative resection in 2010. Results CCL2 and CCL17 were the cytokines most highly expressed by TANs and HCC cell-activated PBNs. Levels of CCL2 and CCL17 messenger RNAs and proteins were significantly higher in TANs than in PBNs, and increased in patients with HCC recurrence. CCL2 and CCL17 messenger RNA and proteins also increased when PBNs were exposed to conditioned media from HCC cell lines. Immunohistochemical analysis of a tissue microarray showed that CCL2+ and CCL17+ cells, which also expressed the neutrophil marker CD66b, were distributed throughout the HCC stroma, but not in tumor cells or the adjacent nontumor liver cells. The number of CCL2+ or CCL17+ TANs correlated with tumor size, microvascular invasion, tumor encapsulation, tumor differentiation, and stage. Patients whose tumors had lower levels of CCL2+ or CCL17+ cells had longer survival times than those with higher numbers of these cells. TAN-conditioned media, as well as recombinant CCL2 and CCL17, increased the migratory activity of the macrophages and T-regulatory (Treg) cells from patients or mice with HCC to a greater extent that PBN-conditioned media. Neutralizing antibodies against CCL2 and CCL17, or their receptors C-C chemokine receptor 2 and C-C chemokine receptor 4, reduced the migratory activities of macrophage and Treg cells. HCC cell lines injected into mice formed larger tumors when they were co-injected with TANs and formed more pulmonary metastases; these tumors were infiltrated by Ly6G+ cells, F4/80+ macrophages, and Foxp3+ Treg cells. In a phosphokinase array of human PBNs, levels of phosphorylated AKT and P38 increased after exposure to conditioned media from all 4 HCC cell types. Pharmacologic inhibitors of AKT and P38 inhibited secretion of CCL2 and CCL17 by these PBNs. In tumor-bearing mice, sorafenib increased the numbers of TANs and levels of CCL2 and CCL17 in tumors. HCC tissues from patients who received sorafenib before surgery contained more TANs than tissues from patients who did not receive sorafenib. In knockdown cells, HCC cell–derived CXCL5 was the strongest effector of neutrophil migration under hypoxic conditions. In mice, the combination of sorafenib and TAN depletion inhibited tumor growth and neovascularization to a greater extent than sorafenib alone. Conclusions TANs recruit macrophages and Treg cells to HCCs to promote their growth, progression, and resistance to sorafenib.
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