F4/80+Ly6Chigh Macrophages Lead to Cell Plasticity and Cancer Initiation in Colitis.

BACKGROUND & AIMS: Colorectal cancer is a leading cause of cancer death, and a major risk factor is chronic inflammation. Despite the link between colitis and cancer, the mechanism by which inflammation leads to colorectal cancer is not well understood. METHODS: To investigate whether different forms of inflammation pose the same risk of cancer, we compared several murine models of colitis (dextran sodium sulfate [DSS], 2,4,6-trinitrobenzene sulfonic acid, 4-ethoxylmethylene-2-phenyloxazol-5-one, Citrobacter rodentium, Fusobacterium nucleatum, and doxorubicin) with respect to their ability to lead to colonic tumorigenesis. We attempted to correlate the severity of colitis and inflammatory profile with the risk of tumorigenesis in both azoxymethane-dependent and Dclk1/APCfl/fl murine models of colitis-associated cancer. RESULTS: DSS colitis reproducibly led to colonic tumors in both mouse models of colitis-associated cancer. In contrast, all other forms of colitis did not lead to cancer. When compared with the colitis not associated with tumorigenesis, DSS colitis was characterized by significantly increased CD11b+F4/80+Ly6Chigh macrophages and CD11b+Ly6G+ neutrophils. Interestingly, depletion of the CD11b+F4/80+Ly6Chigh macrophages inhibited tumorigenesis, whereas depletion of CD11b+Ly6G+ neutrophils had no effect on tumorigenesis. Furthermore, the macrophage-derived cytokines interleukin-1ß, tumor necrosis factor-α, and interleukin-6 were significantly increased in DSS colitis and promoted stemness of Dclk1+ tuft cells that serve as the cellular origin of cancer. CONCLUSIONS: We have identified CD11b+F4/80+Ly6Chigh macrophages as key mediators of cancer initiation in colitis-associated cancer. Development of new therapies that target these cells may provide an effective preventative strategy for colitis-associated cancer.

Regulation of cluster synchronization in multilayer networks of delay coupled semiconductor lasers with the use of disjoint layer symmetry.

In real-world complex systems, heterogeneous components often interact in complex connection patterns and could be schematized by a formalism of multilayer network. In this work, the synchronization characteristics of multilayer network composed of semiconductor lasers (SLs) are investigated systematically. It is demonstrated that the interplay between different layers plays an important role on the synchronization patterns. We elucidate that the performance of cluster synchronization could be facilitated effectively with the introduction of disjoint layer symmetry into network topology. Intertwined stability of clusters from different layers could be decoupled into independent, and the parameter spaces for stable synchronization are extended significantly. The robustness of our proposed regulation scheme on operation parameters is numerically evaluated. Furthermore, the generality of presented theoretical results is validated in networks with more complex topology and multiple layers.

MiR-181a-5p may regulate cell proliferation and autophagy in myopia and the associated retinopathy.

The mechanism of myopia and the associated retinopathy remains unclear, and dysregulated microRNAs (miRNAs) are implicated in this disease. In this research, we purposed to find out the regulatory function that miRNAs play in myopia and the associated retinopathy. We first performed miRNA microarray analysis in a lens-induced myopia mouse model and found that miR-9-5p, miR-96-5p, miR-182-5p, miR-183-5p, and miR-181a-5p were elevated in the myopic retina. Then, we examined the functions and regulatory mechanisms of miR-181a-5p utilizing the human retinal pigment epithelium (RPE) cell line ARPE-19 by overexpressing miR-181a-5p. RNA sequencing (RNA-Seq) and qRT-PCR analysis were employed to identify differentially expressed genes after transfection. The qRT‒PCR outcomes, immunoblotting, and immunofluorescence indicated that the SGSH expression was significantly hindered through miR-181a-5p overexpression. MiR-181a-5p overexpression has the ability to elevate RPE cell proliferation and induce autophagy by targeting SGSH. We validated the negative influence of miR-181a-5p on the SGSH expression through luciferase reporter assays, which demonstrated its ability to target the 3' untranslated region of SGSH. The reversal of implications of miR-181a-5p overexpression was achieved through SGSH upregulation. We provided novel perspectives into the miR-181a-5p function in regulating myopia development and may serve as a target for therapy and molecular biomarker for myopia.

CircRNA expression profiles and regulatory networks in the vitreous humor of people with high myopia.

Myopia is a global health and economic issue. Circular RNAs (circRNAs) have been shown to play an important role in the pathogenesis of many ocular diseases. We first evaluated the circRNA profiles and possible roles in vitreous humor samples of individuals with high myopia by a competitive endogenous RNA (ceRNA) array. Vitreous humor samples were collected from 15 high myopic (5 for ceRNA array, and 10 for qPCR) and 15 control eyes (5 for ceRNA array, and 10 for qPCR) with idiopathic epiretinal membrane (ERM) and macular hole (MH). 486 circRNAs (339 upregulated and 147 downregulated) and 264 mRNAs (202 upregulated and 62 downregulated) were differentially expressed between the high myopia and control groups. The expression of hsa_circ_0033079 (hsa-circDicer1), hsa_circ_0029989 (hsa-circNbea), hsa_circ_0019072 (hsa-circPank1) and hsa_circ_0089716 (hsa-circEhmt1) were validated by qPCR. Pearson analysis and multivariate regression analysis showed positive and significant correlations for axial length with hsa-circNbea and hsa-circPank1. KEGG analysis showed that the target genes of circRNAs were enriched in the mTOR, insulin, cAMP, and VEGF signaling pathways. GO analysis indicated that circRNAs mainly targeted transcription, cytoplasm, and protein binding. CircRNA-associated ceRNA network analysis and PPI network analysis identified several critical genes for myopia. The expression of circNbea, circPank1, miR-145-5p, miR-204-5p, Nras, Itpr1 were validated by qPCR in the sclera of form-deprivation myopia (FDM) mice model. CircPank1/miR-145-5p/NRAS and circNbea/miR-204-5p/ITPR1 were identified and may be important in the progression of myopia. Our findings suggest that circRNAs may contribute to the pathogenesis of myopia and may serve as potential biomarkers.

Numerical and experimental investigation of a dispersive optoelectronic oscillator for chaotic time-delay signature suppression.

Chaos generation from a novel single-loop dispersive optoelectronic oscillator (OEO) with a broadband chirped fiber Bragg grating (CFBG) is numerically and experimentally investigated. The CFBG has much broader bandwidth than the chaotic dynamics such that its dispersion effect rather than filtering effect dominates the reflection. The proposed dispersive OEO exhibits chaotic dynamics when sufficient feedback strength is guaranteed. Suppression of chaotic time-delay signature (TDS) is observed as the feedback strength increases. The TDS can be further suppressed as the amount of grating dispersion increases. Without compromising bandwidth performance, our proposed system extends the parameter space of chaos, enhances the robustness to modulator bias variation, and improves TDS suppression by at least five times comparing to the classical OEO. Experimental results qualitatively agree well with numerical simulations. In addition, the advantage of dispersive OEO is further verified by experimentally demonstrating random bit generation with tunable rate up to 160 Gbps.

Photonic reservoir computing using a self-injection locked semiconductor laser under narrowband optical feedback.

Photonic time-delay reservoir computing (TDRC) using a self-injection locked semiconductor laser under optical feedback from a narrowband apodized fiber Bragg grating (AFBG) is proposed and numerically demonstrated. The narrowband AFBG suppresses the laser's relaxation oscillation and provides self-injection locking in both the weak and strong feedback regimes. By contrast, conventional optical feedback provides locking only in the weak feedback regime. The TDRC based on self-injection locking is first evaluated by the computational ability and memory capacity, then benchmarked by the time series prediction and channel equalization. Good computing performances can be achieved using both the weak and strong feedback regimes. Interestingly, the strong feedback regime broadens the usable feedback strength range and improves robustness to feedback phase variations in the benchmark tests.

Effects of mixed nut consumption on LDL cholesterol, lipoprotein(a), and other cardiometabolic risk factors in overweight and obese adults.

BACKGROUND AND AIMS: Elevated LDL-C, lipoprotein(a) [Lp(a)], and inflammation are associated with greater risk for atherosclerotic cardiovascular events. Consumption of individual nut types decreases these risk factors but knowledge about the effect of mixed nuts on Lp(a) is limited. The objective of this study was to determine the effects of consuming 42.5 g/day of mixed nuts on LDL-C, Lp(a), and inflammatory markers in individuals with overweight or obesity. METHODS AND RESULTS: In a 16-week randomized control trial, 29 participants with overweight or obesity (BMI 25-40 kg/m2) consumed either 42.5 g/day of mixed nuts (cashews, almonds, macadamia nuts, Brazil nuts, pecans, pistachios, walnuts, and peanuts) or 69 g/day isocaloric pretzels. Blood samples were collected at baseline, week 8, and week 16 for analysis on total cholesterol (TC), LDL-C, Lp(a), inflammation markers, glucose, insulin, adiponectin and liver function enzymes. No significant differences were seen in TC, LDL-C, HDL-C, Lp(a), or liver function enzymes between the two groups. Participants consuming mixed nuts had significantly lower body fat percentage and diastolic blood pressure, and higher adiponectin (all P ≤ 0.05). C-reactive protein (CRP) and 8-oxo-deoxyguanosis (8-oxodG) showed non-significant decreasing trends and total antioxidant capacity (TAC) had a non-significant increasing trend in the mixed nut group. CONCLUSION: Consumption of mixed nuts had no evidence of an effect on LDL-C or Lp(a) throughout the intervention. Notably, mixed nut consumption lowered body fat percentage without significant changes in body weight or BMI. Future studies with larger sample sizes investigating the changing trends of CRP, 8-oxodG, and TAC are warranted. CLINICAL TRIAL REGISTER: NCT03375866.

Hybrid Catalyst Coupling Single-Atom Ni and Nanoscale Cu for Efficient CO2 Electroreduction to Ethylene.

A hybrid catalyst with integrated single-atom Ni and nanoscale Cu catalytic components is reported to enhance the C-C coupling and ethylene (C2H4) production efficiency in the electrocatalytic CO2 reduction reaction (eCO2RR). The single-atom Ni anchored on high-surface-area ordered mesoporous carbon enables high-rate and selective conversion of CO2 to CO in a wide potential range, which complements the subsequent CO enrichment on Cu nanowires (NWs) for the C-C coupling to C2H4. In situ surface-enhanced infrared absorption spectroscopy (SEIRAS) confirms the substantially improved CO enrichment on Cu, once the incorporation of single-atom Ni occurs. Also, in situ X-ray absorption near-edge structure (XANES) demonstrates the structural stability of the hybrid catalyst during eCO2RR. By modulating hybrid compositions, the optimized catalyst shows 66% Faradaic efficiency (FE) in an alkaline flow cell with over 100 mA·cm-2 at -0.5 V versus reversible hydrogen electrode, leading to a five-order enhancement in C2H4 selectivity compared with single-component Cu NWs.

Strong cluster synchronization in complex semiconductor laser networks with time delay signature suppression.

Cluster synchronization is a state where clusters of nodes inside the network exhibit isochronous synchronization. Here, we present a mechanism to realize the strong cluster synchronization in semiconductor laser (SL) networks with complex topology, where stable cluster synchronization is achieved with decreased correlation between dynamics of different clusters and time delay signature concealment. We elucidate that, with the removal of intra-coupling within clusters, the stability of cluster synchronization could be enhanced effectively, while the statistical correlation among dynamics of each cluster decreases. Moreover, it is demonstrated that the correlation between clusters can be further reduced with the introduction of dual-path injection and frequency detuning. The robustness of strong cluster synchronization on operation parameters is discussed systematically. Time delay signature in chaotic outputs of SL network is concealed simultaneously with heterogeneous inter-coupling among different clusters. Our results suggest a new approach to control the cluster synchronization in complex SL networks and may potentially lead to new network solutions for communication schemes and encryption key distribution.

Hierarchical-dependent cluster synchronization in directed networks with semiconductor lasers.

Cluster synchronization in complex networks with mutually coupled semiconductor lasers (SLs) has recently been extensively studied. However, most of the previous works on cluster synchronization patterns have concentrated on undirected networks. Here, we numerically study the complete cluster synchronization patterns in directed networks composed of SLs, and demonstrate that the values of the SLs parameter and network parameter play a prominent role on the formation and stability of cluster synchronization patterns. Moreover, it is shown that there is a hierarchical dependency between the synchronization stability of different clusters in directed networks. The stability of one cluster can be affected by another cluster, but not vice versa. Without loss of generality, the results are validated in another SLs network with more complex topology.

Blue light attenuates TGF-ß2-induced epithelial-mesenchymal transition in human lens epithelial cells via autophagy impairment.

BACKGROUND: Pathogenesis of posterior capsular opacification (PCO) was related to pathological epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs). It has been reported that blue light could have an effect on EMT. This study aims to elucidate the role and potential mechanism of autophagy in EMT after blue light exposure in LECs. METHODS: HLE-B3 cells were treated with TGF-ß2 with different concentration and time to induce EMT as a model of PCO in vitro. Cells were exposed to blue light with or without TGF-ß2. The expression levels of EMT-associated markers were analyzed by qRT-PCR, western blotting and cell migration ability was determined by transwell migration assay and wound healing assay. The expressions of autophagy-related proteins were analyzed by western blotting, immunofluorescence and transmission electron microscopy. Rapamycin and chloroquine were utilized in cells for autophagy activation and inhibition. RESULTS: TGF-ß2 induced autophagy activation during EMT progression in HLE-B3 cells in a dose- and time-dependent manner. Blue light exposure inhibited TGF-ß2-induced EMT characterized by inhibited expression of EMT related markers and reduced migration capacity. Meanwhile, blue light exposure impaired autophagy activated by TGF-ß2. Furthermore, Autophagy activation with rapamycin rescued EMT attenuated by blue light. Autophagy inhibition with chloroquine reduced TGF-ß2-induced EMT in HLE-B3 cells. CONCLUSION: Blue light exposure had inhibited effects on TGF-ß2-induced EMT in LECs through autophagy impairment, which provides a new insight on prevention and treatment of PCO.

Functions of retinal astrocytes and Müller cells in mammalian myopia.

BACKGROUND: Changes in the retina and choroid blood vessels are regularly observed in myopia. However, if the retinal glial cells, which directly contact blood vessels, play a role in mammalian myopia is unknown. We aimed to explore the potential role and mechanism of retinal glial cells in form deprived myopia. METHODS: We adapted the mice form-deprivation myopia model by covering the right eye and left the left eye open for control, measured the ocular structure with anterior segment optical coherence tomography, evaluated changes in the morphology and distribution of retinal glial cells by fluorescence staining and western blotting; we also searched the online GEO databases to obtain relative gene lists and confirmed them in the form-deprivation myopia mouse retina at mRNA and protein level. RESULTS: Compared with the open eye, the ocular axial length (3.54 ± 0.006 mm v.s. 3.48 ± 0.004 mm, p = 0.027) and vitreous chamber depth (3.07 ± 0.005 mm v.s. 2.98 ± 0.006 mm, p = 0.007) in the covered eye became longer. Both glial fibrillary acidic protein and excitatory amino acid transporters 4 elevated. There were 12 common pathways in human myopia and anoxic astrocytes. The key proteins were also highly relevant to atropine target proteins. In mice, two common pathways were found in myopia and anoxic Müller cells. Seven main genes and four key proteins were significantly changed in the mice form-deprivation myopia retinas. CONCLUSION: Retinal astrocytes and Müller cells were activated in myopia. They may response to stimuli and secretory acting factors, and might be a valid target for atropine.

The effects of colour and temporal frequency of flickering light on variability of the accommodation response in emmetropes and myopes.

BACKGROUND: Myopia is hypothesized to be influenced by environmental light conditions. For example, it has been shown that colour and temporal frequency of flickering light affect emmetropisation in animals. Considering the omnipresence of flickering light in our daily life, we decided to analyze the effect of colour flickers on variability of the accommodation response (VAR) in emmetropes and myopes. METHODS: We measured the dynamic accommodative responses of 19 emmetropic and 22 myopic adults using a Grand Seiko WAM-5500 open-field autorefractor. The subjects focused for more than 20 s on a black Snellen E target against three different backgrounds made up of three colour flicker combinations (red/green, red/blue and blue/green) and under five frequency conditions (0.20 Hz, 0.50 Hz, 1.00 Hz, 1.67 Hz, and 5.00 Hz). RESULTS: Flicker frequency and colour both had a significant effect on VAR. Lower frequencies were associated with larger variability. Colour had an effect only at low frequencies, and red/blue colour flicker resulted in the largest variability. The variability in myopes were larger than those in emmetropes. CONCLUSIONS: These findings support the hypothesis that further studies on the colour and temporal frequency of flickering light can lead to a better understanding of the development and progression of myopia.

Isochronous cluster synchronization in delay-coupled VCSEL networks subjected to variable-polarization optical injection with time delay signature suppression.

The isochronous cluster synchronization with time delay (TD) signature suppression in delay-coupled vertical-cavity surface-emitting laser (VCSEL) networks subject to variable-polarization optical injection (VPOI) is theoretically and numerically studied. Based on the inherent symmetries of network topology, parameter spaces for stable cluster synchronization are presented, and zero-lag synchronization are achieved for VCSELs in same clusters. Additionally, the TD signature reduction for the dynamics of VCSELs in the stable clusters are systematically discussed. It is shown that both moderate polarizer angle and frequency detuning between different clusters have strengthen the effect of TD signature suppression. Moreover, the isochronous cluster synchronization with TD signature concealment is also verified in another VPOI-VCSEL network with different topology, indicating the generality of proposed results. Our results shed a new light on the research of chaos synchronization and chaos-based secure communications in VCSEL networks.

Common-injection-induced isolated desynchronization in delay-coupled VCSELs networks with variable-polarization optical feedback.

We have investigated the cluster isolated desynchronization, a symmetry-breaking state, in the delay-coupled vertical-cavity surface-emitting lasers (VCSELs) networks subject to variable-polarization optical feedback (VPOF). It is shown that, in the VPOF-VCSELs networks, the elusive isolated desynchronization phenomenon could emerge out of the cluster synchronization by the common-signal injection approach from an additional auxiliary VCSEL. The influences of parameters in VPOF-VCSELs networks on the existence and stability of isolated desynchronization are systematically investigated. Moreover, the generality of the proposed scheme is validated in the VPOF-VCSELs network with real-world network topology (Nepal power grid network). Our results offer a new insight to manage the synchronization patterns of a VCSELs network.

Cluster synchronization in symmetric VCSELs networks with variable-polarization optical feedback.

The cluster synchronization of mutually coupled vertical-cavity surface-emitting lasers (VCSELs) networks subject to variable-polarization optical feedback (VPOF) with symmetric structure is theoretically investigated. Zero-lag synchronization could be achieved between different VCSELs within same cluster in such networks, which is solely derived from the intrinsic symmetry of network topology. The influences of significant parameters of VCSELs networks on the stability of cluster synchronization are further discussed. Moreover, it is shown that the polarizer angle of optical feedback in VCSELs plays a particularly important role on the formation of cluster.

Publisher's Note: Incoherence-Mediated Remote Synchronization [Phys. Rev. Lett. 118, 174102 (2017)].

This corrects the article DOI: 10.1103/PhysRevLett.118.174102.

Incoherence-Mediated Remote Synchronization.

In previously identified forms of remote synchronization between two nodes, the intermediate portion of the network connecting the two nodes is not synchronized with them but generally exhibits some coherent dynamics. Here we report on a network phenomenon we call incoherence-mediated remote synchronization (IMRS), in which two noncontiguous parts of the network are identically synchronized while the dynamics of the intermediate part is statistically and information-theoretically incoherent. We identify mirror symmetry in the network structure as a mechanism allowing for such behavior, and show that IMRS is robust against dynamical noise as well as against parameter changes. IMRS may underlie neuronal information processing and potentially lead to network solutions for encryption key distribution and secure communication.

AtrbohD and AtrbohF negatively regulate lateral root development by changing the localized accumulation of superoxide in primary roots of Arabidopsis.

MAIN CONCLUSION: NADPH oxidase AtrbohD an d AtrbohF negatively modulate lateral root development by changing the peroxidase activity and increasing the local generation of superoxide in primary roots of Arabidopsis in an auxin-independent manner. NADPH oxidase subunits AtrbohD and AtrbohF play pivotal roles in regulating growth, development and stress responses in Arabidopsis. However, whether they modulate lateral root (LR) formation has not yet been addressed, and the detailed mechanisms underlying the process remain unanswered. Here, we show that two null double mutants atrbohD1/F1 and atrbohD2/F2, in which both AtrbohD and AtrbohF genes are disrupted, had remarkably higher LR density than wild-type (WT), or the single mutant atrbohD1 and atrbohF1. Compared to WT, the double mutants exhibited early emerged LRs and enhanced density of lateral root primordia (LRP). Unexpectedly, the production of superoxide (O2 (-)), but not hydrogen peroxide, in the mature area of the primary root containing LRs significantly increased in the double mutants relative to that in WT. Further experiments revealed that the local accumulation of O2 (-) led to the enhancement of LR density in the double mutants. Moreover, the deficiency of AtrbohD and AtrbohF caused a marked increase in peroxidase activity in the mature root zone, which contributed to the localized accumulation of O2 (-) and the elevated LR density in the double mutants. Furthermore, the double mutants were not sensitive to exogenous auxin naphthalene acetic acid or auxin transport inhibitor 1-N-naphthylphthalamic acid in terms of LR formation. The auxin response of LRP in vivo in atrbohD1/F1 was also similar to that in WT. Taken together, these results suggest that AtrbohD and AtrbohF negatively modulate LR development by controlling the local generation of superoxide in an auxin-independent manner. These findings provide new insights into the mechanisms of NADPH oxidase-mediated regulation of LR branching in Arabidopsis.

Depletion of Kcnq1ot1 non-coding RNA does not affect imprinting maintenance in stem cells.

To understand the complex regulation of genomic imprinting it is important to determine how early embryos establish imprinted gene expression across large chromosomal domains. Long non-coding RNAs (ncRNAs) have been associated with the regulation of imprinting domains, yet their function remains undefined. Here, we investigated the mouse Kcnq1ot1 ncRNA and its role in imprinted gene regulation during preimplantation development by utilizing mouse embryonic and extra-embryonic stem cell models. Our findings demonstrate that the Kcnq1ot1 ncRNA extends 471 kb from the transcription start site. This is significant as it raises the possibility that transcription through downstream genes might play a role in their silencing, including Th, which we demonstrate possesses maternal-specific expression during early development. To distinguish between a functional role for the transcript and properties inherent to transcription of long ncRNAs, we employed RNA interference-based technology to deplete Kcnq1ot1 transcripts. We hypothesized that post-transcriptional depletion of Kcnq1ot1 ncRNA would lead to activation of normally maternal-specific protein-coding genes on the paternal chromosome. Post-transcriptional short hairpin RNA-mediated depletion in embryonic stem, trophoblast stem and extra-embryonic endoderm stem cells had no observable effect on the imprinted expression of genes within the domain, or on Kcnq1ot1 imprinting center DNA methylation, although a significant decrease in Kcnq1ot1 RNA signal volume in the nucleus was observed. These data support the argument that it is the act of transcription that plays a role in imprint maintenance during early development rather than a post-transcriptional role for the RNA itself.