Personalized immune subtypes based on machine learning predict response to checkpoint blockade in gastric cancer.

Immune checkpoint inhibitors (ICI) show high efficiency in a small fraction of advanced gastric cancer (GC). However, personalized immune subtypes have not been developed for the prediction of ICI efficiency in GC. Herein, we identified Pan-Immune Activation Module (PIAM), a curated gene expression profile (GEP) representing the co-infiltration of multiple immune cell types in tumor microenvironment of GC, which was associated with high expression of immunosuppressive molecules such as PD-1 and CTLA-4. We also identified Pan-Immune Dysfunction Genes (PIDG), a conservative PIAM-derivated GEP indicating the dysfunction of immune cell cooperation, which was associated with upregulation of metastatic programs (extracellular matrix receptor interaction, TGF-ß signaling, epithelial-mesenchymal transition and calcium signaling) but downregulation of proliferative signalings (MYC targets, E2F targets, mTORC1 signaling, and DNA replication and repair). Moreover, we developed 'GSClassifier', an ensemble toolkit based on top scoring pairs and extreme gradient boosting, for population-based modeling and personalized identification of GEP subtypes. With PIAM and PIDG, we developed four Pan-immune Activation and Dysfunction (PAD) subtypes and a GSClassifier model 'PAD for individual' with high accuracy in predicting response to pembrolizumab (anti-PD-1) in advance GC (AUC = 0.833). Intriguingly, PAD-II (PIAMhighPIDGlow) displayed the highest objective response rate (60.0%) compared with other subtypes (PAD-I, PIAMhighPIDGhigh, 0%; PAD-III, PIAMlowPIDGhigh, 0%; PAD-IV, PIAMlowPIDGlow, 17.6%; P = 0.003), which was further validated in the metastatic urothelial cancer cohort treated with atezolizumab (anti-PD-L1) (P = 0.018). In all, we provided 'GSClassifier' as a refined computational framework for GEP-based stratification and PAD subtypes as a promising strategy for exploring ICI responders in GC. Metastatic pathways could be potential targets for GC patients with high immune infiltration but resistance to ICI therapy.

Downregulation of CYRI-B promotes migration, invasion and EMT by activating the Rac1-STAT3 pathway in gastric cancer.

BACKGROUND: CYRI-B plays key roles in regulating cell motility in nontumor cells. However, the role and function of CYRI-B have rarely been studied in cancer cells, including gastric cancer. The purpose of this study was to investigate the clinical significance, biological function and underlying molecular mechanism of CYRI-B in gastric cancer. METHOD: CYRI-B protein levels were detected by immunohistochemistry (IHC) and western blotting (WB). Gastric cancer cells and organoid models were evaluated to explore the correlation of CYRI-B with collagen type I. The function of CYRI-B in proliferation, migration, invasion in gastric cancer was evaluated by in vitro and in vivo experiments. RESULT: CYRI-B protein levels were downregulated in gastric cancer. Low expression of CYRI-B was related to later tumor stage and poorer prognosis. CYRI-B expression was reduced when cells were cultured in collagen type I, which was mediated by collagen receptor DDR1. Knockdown of CYRI-B promoted migration, invasion and EMT in vivo and in vitro. Mechanistically, knockdown of CYRI-B activated the Rac1-STAT3 pathway. CONCLUSION: Our findings showed that CYRI-B plays an important role in the tumor microenvironment, and is associated with malignant characteristics acquired by gastric cancer. This study may provide new targets for future therapeutic interventions for tumor metastasis.

Alterations in spatiotemporal characteristics of dynamic networks in juvenile myoclonic epilepsy.

BACKGROUND: Juvenile myoclonic epilepsy (JME) is characterized by altered patterns of brain functional connectivity (FC). However, the nature and extent of alterations in the spatiotemporal characteristics of dynamic FC in JME patients remain elusive. Dynamic networks effectively encapsulate temporal variations in brain imaging data, offering insights into brain network abnormalities and contributing to our understanding of the seizure mechanisms and origins. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) data were procured from 37 JME patients and 37 healthy counterparts. Forty-seven network nodes were identified by group-independent component analysis (ICA) to construct the dynamic network. Ultimately, patients' and controls' spatiotemporal characteristics, encompassing temporal clustering and variability, were contrasted at the whole-brain, large-scale network, and regional levels. RESULTS: Our findings reveal a marked reduction in temporal clustering and an elevation in temporal variability in JME patients at the whole-brain echelon. Perturbations were notably pronounced in the default mode network (DMN) and visual network (VN) at the large-scale level. Nodes exhibiting anomalous were predominantly situated within the DMN and VN. Additionally, there was a significant correlation between the severity of JME symptoms and the temporal clustering of the VN. CONCLUSIONS: Our findings suggest that excessive temporal changes in brain FC may affect the temporal structure of dynamic brain networks, leading to disturbances in brain function in patients with JME. The DMN and VN play an important role in the dynamics of brain networks in patients, and their abnormal spatiotemporal properties may underlie abnormal brain function in patients with JME in the early stages of the disease.

The role of neurotransmitters in mediating the relationship between brain alterations and depressive symptoms in patients with inflammatory bowel disease.

A growing body of evidence from neuroimaging studies suggests that inflammatory bowel disease (IBD) is associated with functional and structural alterations in the central nervous system and that it has a potential link to emotional symptoms, such as anxiety and depression. However, the neurochemical underpinnings of depression symptoms in IBD remain unclear. We hypothesized that changes in cortical gamma-aminobutyric acid (GABA+) and glutamine (Glx) concentrations are related to cortical thickness and resting-state functional connectivity in IBD as compared to healthy controls. To test this, we measured whole-brain cortical thickness and functional connectivity within the medial prefrontal cortex (mPFC), as well as the concentrations of neurotransmitters in the same brain region. We used the edited magnetic resonance spectroscopy (MRS) with the MEGA-PRESS sequence at a 3 T scanner to quantitate the neurotransmitter levels in the mPFC. Subjects with IBD (N = 37) and healthy control subjects (N = 32) were enrolled in the study. Compared with healthy controls, there were significantly decreased GABA+ and Glx concentrations in the mPFC of patients with IBD. The cortical thickness of patients with IBD was thin in two clusters that included the right medial orbitofrontal cortex and the right posterior cingulate cortex. A seed-based functional connectivity analysis indicated that there was higher connectivity of the mPFC with the left precuneus cortex (PC) and the posterior cingulate cortex, and conversely, lower connectivity in the left frontal pole was observed. The functional connectivity between the mPFC and the left PC was negatively correlated with the IBD questionnaire score (r = -0.388, p = 0.018). GABA+ concentrations had a negative correlation with the Hamilton Depression Scale (HAMD) score (r = -0.497, p = 0.002). Glx concentration was negatively correlated with the HAMD score (r = -0.496, p = 0.002) and positively correlated with the Short-Form McGill Pain Questionnaire score (r = 0.330, p = 0.046, uncorrected). There was a significant positive correlation between the ratio of Glx to GABA+ and the HAMD score (r = 0.428, p = 0.008). Mediation analysis revealed that GABA+ significantly mediated the main effect of the relationship between the structural and functional alterations and the severity of depression in patients with IBD. Our study provides initial evidence of neurochemistry that can be used to identify potential mechanisms underlying the modulatory effects of GABA+ on the development of depression in patients with IBD.

Monolithic silicon photonic 32x32 thin-CLOS AWGR for all-to-all interconnections.

This paper reports the design, fabrication, and experimental demonstration of a monolithic silicon photonic (SiPh) 32×32 Thin-CLOS arrayed waveguide grating router (AWGR) for scalable SiPh all-to-all interconnection fabrics. The 32×32 Thin-CLOS makes use of four 16-port silicon nitride AWGRs, which are compactly integrated and interconnected by a multi-layer waveguide routing method. The fabricated Thin-CLOS has 4 dB insertion loss, < -15 dB adjacent channel crosstalk, and < -20 dB non-adjacent channel crosstalk. System experiments operated on the 32×32 SiPh Thin-CLOS demonstrate error-free communication at 25 Gb/s.

CT for the evaluation of myocardial extracellular volume with MRI as reference: a systematic review and meta-analysis.

OBJECTIVE: Myocardial extracellular volume (ECV) fraction is an important imaging biomarker in clinical decision-making. CT-ECV is a potential alternative to MRI for ECV quantification. We conducted a meta-analysis to comprehensively assess the reliability of CT for ECV quantification with MRI as a reference. METHODS: We systematically searched PubMed, EMBASE, and the Cochrane Library for relevant articles published since the establishment of the database in July 2022. The articles comparing CT-ECV with MRI as a reference were included. Meta-analytic methods were applied to determine the pooled weighted bias, limits of agreement (LOA), and correlation coefficient (r) between CT-ECV and MRI-ECV. RESULTS: Seventeen studies with a total of 459 patients and 2231 myocardial segments were included. The pooled mean difference (MD), LOA, and r for ECV quantification at the per-patient level was (0.07%; 95% LOA: - 0.42 to 0.55%) and 0.89 (95% CI: 0.86-0.91), respectively, while on the per-segment level was (0.44%; 95% LOA: 0.16-0.72%) and 0.84 (95% CI: 0.82-0.85), respectively. The pooled r from studies with the ECViodine method for ECV quantification was significantly higher compared to those with the ECVsub method (0.94 (95% CI: 0.91-0.96) vs. 0.84 (95% CI: 0.80-0.88), respectively, p = 0.03). The pooled r from septal segments was significantly higher than those from non-septal segments (0.88 (95% CI: 0.86-0.90) vs. 0.76 (95% CI: 0.71-0.90), respectively, p = 0.009). CONCLUSION: CT showed a good agreement and excellent correlation with MRI for ECV quantification and is a potentially attractive alternative to MRI. CLINICAL RELEVANCE STATEMENT: The myocardial extracellular volume fraction can be acquired using a CT scan, which is not only a viable alternative to myocardial extracellular volume fraction derived from MRI but is also less time-consuming and costly for patients. KEY POINTS: • Noninvasive CT-ECV is a viable alternative to MRI-ECV for ECV quantification. • CT-ECV using the ECViodine method showed more accurate myocardial ECV quantification than ECVsub. • Septal myocardial segments showed lower measurement variability than non-septal segments for the ECV quantification.

Association of aberrant brain network dynamics with gut microbial composition uncovers disrupted brain-gut-microbiome interactions in irritable bowel syndrome: Preliminary findings.

BACKGROUND AND PURPOSE: Growing evidence suggests that abnormalities in brain-gut-microbiome (BGM) interactions are involved in the pathogenesis of irritable bowel syndrome (IBS). Our study aimed to explore alterations in dynamic functional connectivity (DFC), the gut microbiome and the bidirectional interaction in the BGM. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI), fecal samples and clinical chacteristics were collected from 33 IBS patients and 32 healthy controls. We performed a systematic DFC analysis on rs-fMRI. The gut microbiome was analyzed by 16S rRNA gene sequencing. Associations between DFC characteristics and microbial alterations were explored. RESULTS: In the DFC analysis, four dynamic functional states were identified. IBS patients exhibited increased mean dwell and fraction time in State 4, and reduced transitions from State 3 to State 1. Aberrant temporal properties in State 4 were only evident when choosing a short window (36 s or 44 s). Decreased functional connectivity (FC) variability was found in State 1 and State 3 in IBS patients, two of which (independent component [IC]51-IC91, IC46-IC11) showed significant correlations with clinical characteristics. Additionally, we identified nine significantly differential abundances in microbial composition. We also found that IBS-related microbiota were associated with aberrant FC variability, although these exploratory results were obtained at an uncorrected threshold of significance. CONCLUSIONS: Although future studies are needed to confirm our results, the findings not only provide a new insight into the dysconnectivity hypothesis in IBS from a dynamic perspective, but also establish a possible link between DFC and the gut microbiome, which lays the foundation for future research on disrupted BGM interactions.

Aberrant dynamic structure-function relationship of rich-club organization in treatment-naïve newly diagnosed juvenile myoclonic epilepsy.

Neuroimaging studies have shown that juvenile myoclonic epilepsy (JME) is characterized by impaired brain networks. However, few studies have investigated the potential disruptions in rich-club organization-a core feature of the brain networks. Moreover, it is unclear how structure-function relationships dynamically change over time in JME. Here, we quantify the anatomical rich-club organization and dynamic structural and functional connectivity (SC-FC) coupling in 47 treatment-naïve newly diagnosed patients with JME and 40 matched healthy controls. Dynamic functional network efficiency and its association with SC-FC coupling were also calculated to examine the supporting of structure-function relationship to brain information transfer. The results showed that the anatomical rich-club organization was disrupted in the patient group, along with decreased connectivity strength among rich-club hub nodes. Furthermore, reduced SC-FC coupling in rich-club organization of the patients was found in two functionally independent dynamic states, that is the functional segregation state (State 1) and the strong somatomotor-cognitive control interaction state (State 5); and the latter was significantly associated with disease severity. In addition, the relationships between SC-FC coupling of hub nodes connections and functional network efficiency in State 1 were found to be absent in patients. The aberrant dynamic SC-FC coupling of rich-club organization suggests a selective influence of densely interconnected network core in patients with JME at the early phase of the disease, offering new insights and potential biomarkers into the underlying neurodevelopmental basis of behavioral and cognitive impairments observed in JME.

Long-Term Highly Stable High-Voltage LiCoO2 Synthesized via a Solid Sulfur-Assisted One-Pot Approach.

Commercialized lithium cobalt oxide (LCO) only shows a relatively low capacity of ≈175 mAh g-1 despite a high theoretical capacity of ≈274 mAh g-1 . As an effective and direct strategy, increasing its charge cutoff voltage can, in principle, escalate the capacity, which is however precluded by the irreversible phase transition, oxygen loss, and severe side reactions with electrolytes normally. Herein, an in situ sulfur-assisted solid-state approach is proposed for one-pot synthesis of long-term highly stable high-voltage LCO with a novel compound structure. The coating of coherent spinel Lix Co2 O4 shells on and the gradient doping of SO4 2- polyanions into LCO are in situ realized simultaneously in terms of gas-solid interface reactions between metal oxides and generated SO2 gas from sulfur during synthesis. At 4.6 V, this LCO shows the discharge capacities of 232.4 mAh g-1 at 0.1 C (1 C = 280 mA g-1 ), 215 mAh g-1 at 1 C and 139 mAh g-1 even at 20 C and the capacity retentions of 97.4% (89.7%) after 100 (300) cycles at 1 C. This approach is facile, low-cost and up-scalable and may provide a route to improve the performance of LCO and other electrode materials greatly.

A superior allele of the wheat gene TaGL3.3-5B, selected in the breeding process, contributes to seed size and weight.

KEY MESSAGE: A superior allele of wheat gene TaGL3.3-5B was identified and could be used in marker-assisted breeding in wheat. Identifying the main genes which mainly regulate the yield-associated traits can significantly increase the wheat production. In this study, gene TaGL3.3 was cloned from common wheat according to the sequence of OsPPKL3. A SNP in the 8th exon of TaGL3.3-5B, T/C in coding sequence (CDS), which resulted in an amino acid change (Val/Ala), was identified between the low 1000-kernel weight (TKW) wheat Chinese Spring and the high TKW wheat Xinong 817 (817). Subsequently, association analysis in the mini-core collection (MCC) and the recombinant inbred lines (RIL) revealed that the allele TaGL3.3-5B-C (from 817) was significantly correlated with higher TKW. The high frequency of TaGL3.3-5B-C in the Chinese modern wheat cultivars indicated that it was selected positively in wheat breeding programs. The overexpression of TaGL3.3-5B-C in Arabidopsis resulted in shorter pods and longer grains than those of wild-type counterparts. Additionally, TaGL3.3 expressed a tissue-specific pattern in wheat as revealed by qRT-PCR. We also found that 817 showed higher expression of TaGL3.3 than that in Chinese Spring (CS) during the seed development. These results demonstrate that TaGL3.3 plays an important role in the formation of seed size and weight. Allele TaGL3.3-5B-C is associated with larger and heavier grains that are beneficial to wheat yield improvement.

Construction of a ceRNA network in glioma and analysis of its clinical significance.

BACKGROUND: Glioma is the most common central nervous system tumor with a poor survival rate and prognosis. Previous studies have found that long non-coding RNA (lncRNA) and competitive endogenous RNA (ceRNA) play important roles in regulating various tumor mechanisms. We obtained RNA-Seq data of glioma and normal brain tissue samples from TCGA and GTEx databases and extracted the lncRNA and mRNA expression data. Further, we analyzed these data using weighted gene co-expression network analysis and differential expression analysis, respectively. Differential expression analysis was also carried out on the mRNA data from the GEO database. Further, we predicted the interactions between lncRNA, miRNA, and targeted mRNA. Using the CGGA data to perform univariate and multivariate Cox regression analysis on mRNA. RESULTS: We constructed a Cox proportional hazard regression model containing four mRNAs and performed immune infiltration analysis. Moreover, we also constructed a ceRNA network including 21 lncRNAs, two miRNAs, and four mRNAs, and identified seven lncRNAs related to survival that have not been previously studied in gliomas. Through the gene set enrichment analysis, we found four lncRNAs that may have a significant role in tumors and should be explored further in the context of gliomas. CONCLUSIONS: In short, we identified four lncRNAs with research value for gliomas, constructed a ceRNA network in gliomas, and developed a prognostic prediction model. Our research enhances our understanding of the molecular mechanisms underlying gliomas, providing new insights for developing targeted therapies and efficiently evaluating the prognosis of gliomas.

Tideglusib suppresses stem-cell-like features and progression of osteosarcoma by inhibiting GSK-3ß/NOTCH1 signaling.

Osteosarcoma is the most common primary bone tumor in children, teenagers and adolescents. Cancer stem cells (CSCs) have the function to self-renew and keep the phenotype of tumor, causing clinical treatment failure. Therefore, developing effective therapies to inhibit osteosarcoma progression is urgently necessary. Glycogen synthase kinase 3ß (GSK-3ß)is highly expressed in osteosarcoma. In the present study, we made an exploration on the anti-tumor effect of tideglusib (TID), a small-molecule inhibitor of GSK-3ß, and revealed the underlying mechanisms. Here, we found that TID markedly reduced the cell viability of different osteosarcoma cell lines. Cell cycle arrest distributed in G2/M was markedly up-regulated in TID-incubated osteosarcoma cells through enhancing p21 expression levels. Apoptosis was evidently induced in osteosarcoma cells via blocking Caspase-3 activation. Consistently, tumor growth was effectively suppressed in an established murine xenograft model with few toxicity and side effects in vivo. Furthermore, TID markedly repressed stem-cell-like activity in osteosarcoma cells through down-regulating NOTCH1 expression. Notably, rescuing NOTCH1 significantly abolished the role of TID in reducing cell proliferation and sarcosphere-formation. Mechanistically, we found that TID-inhibited NOTCH1 expression was associated with the blockage of AKT/GSK-3ß signaling pathway. In summary, we for the first time provided evidence that TID could effectively inhibit osteosarcoma progression through repressing cell proliferation, inducing apoptosis, suppressing stem-cell-like properties via down-regulating AKT/GSK-3ß/NOTCH1 signaling pathway. Thus, TID may be a promising therapeutic strategy for osteosarcoma treatment without side effects.

Comprehensive analysis of ceRNA network related to lincRNA in glioblastoma and prediction of clinical prognosis.

BACKGROUND: Long intergenic non-coding RNAs (lincRNAs) are capable of regulating several tumours, while competitive endogenous RNA (ceRNA) networks are of great significance in revealing the biological mechanism of tumours. Here, we aimed to study the ceRNA network of lincRNA in glioblastoma (GBM). METHODS: We obtained GBM and normal brain tissue samples from TCGA, GTEx, and GEO databases, and performed weighted gene co-expression network analysis and differential expression analysis on all lincRNA and mRNA data. Subsequently, we predicted the interaction between lincRNAs, miRNAs, and target mRNAs. Univariate and multivariate Cox regression analyses were performed on the mRNAs using CGGA data, and a Cox proportional hazards regression model was constructed. The ceRNA network was further screened by the DEmiRNA and mRNA of Cox model. RESULTS: A prognostic prediction model was constructed for patients with GBM. We assembled a ceRNA network consisting of 18 lincRNAs, 6 miRNAs, and 8 mRNAs. Gene Set Enrichment Analysis was carried out on four lincRNAs with obvious differential expressions and relatively few studies in GBM. CONCLUSION: We identified four lincRNAs that have research value for GBM and obtained the ceRNA network. Our research is expected to facilitate in-depth understanding and study of the molecular mechanism of GBM, and provide new insights into targeted therapy and prognosis of the tumour.

Calcarine as a bridge between brain function and structure in irritable bowel syndrome: A multiplex network analysis.

BACKGROUND AND AIM: Jointly analyzing structural and functional brain networks enables a better understanding of pathological underpinnings of irritable bowel syndrome (IBS). Multiplex network analysis provides a novel framework to study complex networks consisting of different types of connectivity patterns in multimodal data. METHODS: In the present work, we integrated functional and structural networks to a multiplex network. Then, the multiplex metrics and the inner-layer/inter-layer hub nodes were investigated through 34 patients with IBS and 33 healthy controls. RESULTS: Significantly differential multiplex degree in both left and right parts of calcarine was found, and meanwhile, IBS patients lost inner-layer hub properties in these regions. In addition, the left fusiform was no longer practicing as an inner-layer hub node, while the right median cingulate acted as a new inner-layer hub node in the IBS patients. Besides, the right calcarine, which lost its inner-layer hub identity, became a new inter-layer hub node, and the multiplex degree of the left hippocampus, which lost its inter-layer hub identity in IBS patients, was significantly positively correlated with the IBS Symptom Severity Score scores. CONCLUSIONS: Inner-layer hub nodes of multiplex networks were preferentially vulnerable, and some inner-layer hub nodes would convert into inter-layer hub nodes in IBS patients. Besides, the inter-layer hub nodes might be influenced by IBS severity and therefore converted to general nodes.

Altered brain functional network dynamics in classic trigeminal neuralgia: a resting-state functional magnetic resonance imaging study.

BACKGROUND: Accumulating studies have indicated a wide range of brain alterations with respect to the structure and function of classic trigeminal neuralgia (CTN). Given the dynamic nature of pain experience, the exploration of temporal fluctuations in interregional activity covariance may enhance the understanding of pain processes in the brain. The present study aimed to characterize the temporal features of functional connectivity (FC) states as well as topological alteration in CTN. METHODS: Resting-state functional magnetic resonance imaging and three-dimensional T1-weighted images were obtained from 41 CTN patients and 43 matched healthy controls (HCs). After group independent component analysis, sliding window based dynamic functional network connectivity (dFNC) analysis was applied to investigate specific FC states and related temporal properties. Then, the dynamics of the whole brain topological organization were estimated by calculating the coefficient of variation of graph-theoretical properties. Further correlation analyses were performed between all these measurements and clinical data. RESULTS: Two distinct states were identified. Of these, the state 2, characterized by complicated coupling between default mode network (DMN) and cognitive control network (CC) and tight connections within DMN, was expressed more in CTN patients and presented as increased fractional windows and dwell time. Moreover, patients switched less frequently between states than HCs. Regarding the dynamic topological analysis, disruptions in global graph-theoretical properties (including network efficiency and small-worldness) were observed in patients, coupled with decreased variability in nodal efficiency of anterior cingulate cortex (ACC) in the salience network (SN) and the thalamus and caudate nucleus in the subcortical network (SC). The variation of topological properties showed negative correlation with disease duration and attack frequency. CONCLUSIONS: The present study indicated disrupted flexibility of brain topological organization under persistent noxious stimulation and further highlighted the important role of "dynamic pain connectome" regions (including DMN/CC/SN) in the pathophysiology of CTN from the temporal fluctuation aspect. Additionally, the findings provided supplementary evidence for current knowledge about the aberrant cortical-subcortical interaction in pain development.

Model for cascading failures in functional networks: application to epileptic patients with generalized tonic-clonic seizures.

The dynamic process of epilepsy is modeled as a cascading failure model in functional networks derived from graph theory. The aim is to test whether cascading failure identified from functional magnetic resonance imaging data could simulate epileptic discharges in 18 subjects with generalized tonic-clonic seizure and 17 demographically matched healthy controls. A cascading failure model was used to simulate the neural networks underlying generalized tonic-clonic seizure and healthy controls by stimulation of the node with the greatest number of connections. Results showed that the efficiency of generalized tonic-clonic seizure dropped significantly when compared to controls. Particular nodes whose efficiency altered significantly showed a correlation with the symptoms of generalized tonic-clonic seizure. Results also indicated that the left middle frontal lobe may be a potential focal area in the initiation of generalized tonic-clonic seizure.

Interferometric imaging using Si3N4 photonic integrated circuits for a SPIDER imager.

This paper reports design, fabrication, and experimental demonstration of a silicon nitride photonic integrated circuit (PIC). The PIC is capable of conducting one-dimensional interferometric imaging with twelve baselines near λ = 1100-1600 nm. The PIC consists of twelve waveguide pairs, each leading to a multi-mode interferometer (MMI) that forms broadband interference fringes or each corresponding pair of the waveguides. Then an 18 channel arrayed waveguide grating (AWG) separates the combined signal into 18 signals of different wavelengths. A total of 103 sets of fringes are collected by the detector array at the output of the PIC. We keep the optical path difference (OPD) of each interferometer baseline to within 1 µm to maximize the visibility of the interference measurement. We also constructed a testbed to utilize the PIC for two-dimension complex visibility measurement with various targets. The experiment shows reconstructed images in good agreement with theoretical predictions.

MicroRNA-126 Inhibits Proliferation, Migration, Invasion, and EMT in Osteosarcoma by Targeting ZEB1.

Osteosarcoma (OS) is a tumor with rapid progression, high metastatic potential and poor clinical prognosis. This study was aimed to investigate the function of miR-126 in OS cells. The miR-126 expression in OS cell lines and OS tissues were explored by qRT-PCR. Then, the effects of miR-126 on proliferation, cycle, migration, invasion, and transforming growth factor (TGF)-ß1 induced epithelial to mesenchymal transition (EMT) were assessed. Predicted by TargetScan, one of target genes for miR-126 was verified by luciferase activity assay. Meantime, the mRNA and protein expressions of ZEB1 were assessed by qRT-PCR and Western blot assay. Subsequently, the effect of ZEB1 silence on miR-126 down-regulated cells was also evaluated. Finally, the expressions of key kinases involved in c-Jun N-terminal kinase (JNK) and Janus-activated kinase (JAK)-1/signal transducer and activator of transcription (STAT)-3 pathways were detected by Western blot analysis. Result showed that miR-126 was down-regulated in OS tissues and cell lines. Overexpression of miR-126 significantly inhibited cell proliferation, migration, invasion, and TGF-ß1 induced EMT. The effect of miR-126 knockdown was just the opposite. ZEB1 was predicted and verified as a target gene of miR-126. Meantime, the influence of miR-126 knockdown was abrogated by ZEB1 silence. Additionally, the phosphorylation levels of c-Jun, JNK, JAK1, and STAT3 were down-regulated in miR-126 over-expressed cells, and the effect of miR-126 knockdown was reversed by ZEB1 silence. In conclusion, miR-126 inhibits proliferation, migration, invasion and EMT in OS by targeting ZEB1 through inactivation of JNK and JAK1/STAT3 pathways. J. Cell. Biochem. 118: 3765-3774, 2017. © 2017 Wiley Periodicals, Inc.

Uniform emission, constant wavevector silicon grating surface emitter for beam steering with ultra-sharp instantaneous field-of-view.

We report on uniform emission intensity profile, uniform propagation constant silicon gratings for beam steering application with ultra-sharp instantaneous field-of-view (IFOV). To achieve uniform emission intensity across relatively long emission length, we designed a custom grating with varying Si3N4 width and duty cycle while maintaining a uniform propagation constant for relatively narrow divergence emission pattern. We designed and fabricated the custom Si3N4/Si grating with the varying Si3N4 width/duty cycle together with the reference Si3N4/Si grating with a constant 50:50 duty cycle. The custom grating demonstrated the beam steering angle value of 6.6° by sweeping wavelength between 1530 nm and 1575 nm with the emission length over 1 mm. The measured IFOV based on the 3-dB beamwidth values of the far field patterns for the TE polarization are 0.10° and 0.75° for the custom grating and for the reference grating, respectively. The custom grating also indicates mode-selective behavior due to the perturbation of propagation constant for input modes other than TE polarization. The measured TE-mode to TM-mode suppression ratio for the custom grating is approximately 8.2 dB peak-to-peak measured at far field.