Suppression of Mig-6 overcomes the acquired EGFR-TKI resistance of lung adenocarcinoma.

BACKGROUND: The resistance of lung cancer to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is one of the unconquered frontiers in chemotherapy. Mitogen-inducible gene 6 (Mig-6) is known to inhibit the kinase activity of epidermal growth factor receptor (EGFR). Similarly, numerous studies of mouse models suggested tumor suppressive function of Mig-6 in lung cancer. On the contrary, the results of clinical investigations revealed that lung cancer patients with elevated expression of Mig-6 are associated with a poor prognosis. More recent work showed that unlike wild type (WT) EGFR, mutant EGFR phosphorylates Mig-6 and phosphorylated Mig-6 negatively regulates the degradation of EGFR mutants in lung adenocarcinoma. Here, we tried to untangle the controversies surrounding Mig-6 function as a protagonist or an antagonist of EGFR-TKI resistant lung cancer. METHODS: We compared the expression and phosphorylation status of Mig-6 in the EGFR-TKI resistant lung adenocarcinoma (PC9/GR cells) to EGFR-TKI sensitive lung adenocarcinoma (PC9 cells). We investigated the function of Mig-6 by either depletion or overexpression of Mig-6 in those cells and evaluated the efficacy of combining of Mig-6 knock-down and EGFR-TKI treatment in PC9/GR. The correlation between Mig-6 expressions and the prognoses of lung adenocarcinoma was examined by The Cancer Genome Atlas (TCGA) data and clinical samples. RESULTS: Our results indicated that the expression of Mig-6 was significantly increased in PC9/GR cells compared to that of PC9 cells. The significant portion of Mig-6 existed as a phosphorylated form in PC9 and PC9/GR cells. Moreover, overexpression of Mig-6 significantly increased the cell proliferation, invasion and epithelial mesenchymal transition (EMT) in PC9 cells. Combination of Mig-6 knock-down and EGFR-TKI treatment significantly overcame the EGFR-TKI resistance of PC9/GR cells. In addition, our analyses of clinical samples confirmed that high Mig-6 expressions positively correlate with a poor prognosis and EGFR-TKI resistance in lung adenocarcinoma. CONCLUSION: Our findings reinforce scientific notion of Mig-6 as an oncoprotein in the context of EGFR-TKI resistant lung adenocarcinoma. We propose that targeting Mig-6 may be a promising strategy to overcome the EGFR-TKI resistance in lung cancer.

Clinical significance of atypical protein kinase C (PKCι and PKCζ) and its relationship with yes-associated protein in lung adenocarcinoma.

BACKGROUND: Protein kinase C iota (PKCι) and protein kinase C zeta (PKCζ) are two atypical protein kinase (aPKC) enzymes that contribute to cell proliferation and cancer development. The Hippo/YAP pathway is commonly disrupted and upregulated in cancers. Herein, the expression patterns and clinical relevance of PKCι and PKCζ are evaluated in relation to YAP, a downstream effector of Hippo, in lung adenocarcinoma (LAC). The protein and mRNA expression levels of PKCι, PKCζ, YAP, and their phosphorylated forms, namely p-PKCι, p-PKCζ and p-YAP, are evaluated in relation to clinicopathological factors, including patient survival. METHODS: A total of 200 primary LAC tissue samples were examined by immunohistochemistry for PKCι, p-PKCι, PKCζ, p-PKCζ, YAP, and p-YAP protein expression. Sixty pairs of LAC and non-neoplastic lung tissue samples were assessed for PRKCI, PRKCZ, and YAP mRNA levels. PKCι, p-PKCι, PKCζ, and p-PKCζ protein expression were evaluated by Western blot analysis in the PC9 and PC9/GR LAC cell lines with YAP modulation. RESULTS: LAC demonstrated cytoplasmic PKCι, p-PKCι, PKCζ, and p-PKCζ immunostaining patterns. Positive aPKC protein expressions were related with poor patient survival. Especially, increased p-PKCι protein expression was significantly correlated with higher pathological stage and shortened overall survival. YAP overexpression contributes phosphorylation of PKCι and PKCζ protein expression in the LAC cell line. CONCLUSIONS: PKCι and PKCζ are related to YAP in LAC. PKCι and PKCζ play distinct roles in LAC; specifically, p-PKCι overexpression is suggested to underlie factors that indicate a poor prognosis.

Dual oxidase 1 and NADPH oxidase 2 exert favorable effects in cervical cancer patients by activating immune response.

BACKGROUND: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived reactive oxygen species (ROS) not only can promote cancer progression, but also they have recently emerged as mediators of the mucosal immune system. However, the roles and clinical relevance of the collective or individual NADPH oxidase (NOX) family genes in cervical cancer have not been studied. METHODS: We investigated the clinical significance of the NOX family genes using data from 307 patients with cervical cancer obtained from The Cancer Genome Atlas. Bioinformatics and experimental analyses were performed to examine NOX family genes in cervical cancer patients. RESULTS: Dual Oxidase1 (DUOX1) and Dual Oxidase 2 (DUOX2) mRNA levels were upregulated 57.9- and 67.5-fold, respectively, in cervical cancer patients. The protein expression of DUOX1, DUOX2, and NOX2 also identified in cervical squamous cell carcinoma tissues. Especially, DUOX1 and DUOX2 mRNA levels were significantly increased in patients infected with human papillomavirus (HPV) 16. Moreover, high DUOX1 mRNA levels were significantly associated with both favorable overall survival and disease-free survival in cervical cancer patients. High NOX2 mRNA levels was significantly associated with favorable overall survival. Gene set enrichment analyses revealed that high DUOX1 and NOX2 expression was significantly correlated with the enrichment of immune pathways related to interferon (IFN)-alpha, IFN-gamma, and natural killer (NK) cell signaling. Cell-type identification by estimating relative subsets of known RNA transcript analyses indicated that the fraction of innate immune cells, including NK cells, monocytes, dendritic cells, and mast cells, was elevated in patients with high DUOX1 expression. CONCLUSIONS: DUOX1 and NOX2 expression are associated with mucosal immunity activated in cervical squamous cell carcinoma and predicts a favorable prognosis in cervical cancer patients.

Cytochrome P450 4A11 expression in tumor cells: A favorable prognostic factor for hepatocellular carcinoma patients.

BACKGROUND AND AIM: Elevated cytochrome p450 (CYP) 4A gene expression has been linked to the aggravation of various cancers and affects various regulated metabolites. In hepatocellular carcinoma (HCC), the clinicopathological value of CYP4A has not yet been explored, although CYP4A is expressed at high levels in the liver. The goal of this study was to evaluate the clinicopathological value of CYP4A11 expression in HCC. METHODS: We performed immunohistochemical analysis of CYP4A11 and correlated the results with clinicopathological features of HCC (n = 155). Western blotting and reverse transcription-polymerase chain reaction against CYP4A11 and CYP4A22 were also performed for 15 and 20 pairs of fresh-frozen primary HCC and non-neoplastic liver tissue, respectively. Moreover, we analyzed the underlying mechanism by comparing the high and low CYP4A11 mRNA expression groups using gene set enrichment analysis. RESULTS: CYP4A11 expression level was higher in non-neoplastic hepatocytes than those in HCC cells (P < 0.001), and CYP4A11 expression positively correlated with favorable prognostic factors, including tumor size, histological grade, and pathological tumor stage (P = 0.007, P = 0.005, and P = 0.007). Multivariate analysis revealed that CYP4A11 expression was an independent prognostic factor of overall and disease-free survival (P = 0.002 and P = 0.033). Based on gene set enrichment analysis, high CYP4A11 mRNA expression negatively correlated with the expression of cell cycle-related genes. CONCLUSION: These findings support the notion that CYP4A11 expression is a favorable prognostic factor of HCC and suggest potential predictive diagnostic and prognostic roles of CYP4A11 expression in HCC.

Clinical Significance of the Thioredoxin System and Thioredoxin-Domain-Containing Protein Family in Hepatocellular Carcinoma.

BACKGROUND: Oxidative stress occurs due to the excessive generation of cellular reactive oxygen species and antioxidant system dysfunction. The thioredoxin (TXN) system and TXN-domain-containing protein (TXNDC) family form networks maintaining the cellular reducing environment. Recently, the importance of these genes in the tumor environment has been emphasized. AIM: To investigate the clinical significance of TXNs and TXNDC family members in HCC. METHODS: Genomic data from 367 hepatocellular carcinoma (HCC) patients who underwent hepatic resections were analyzed to determine genetic alterations in mRNA and protein levels between patients and healthy controls. In addition, functional enrichment and survival analyses were performed. RESULTS: HCC patients were shown to have enhanced expression of TXN, TXNRD1, and TXNDC7/9/14 mRNA and protein compared with controls. In accordance with the survival analyses, strong associations were found that patients with TXN, TXNRD1, and TXNDC1/7/9 alterations were proven to have poor prognosis in overall survival. Moreover, gene set enrichment analysis and network analyses revealed that positive correlations were found in mRNA expression of TXN, TXNRD1, and TXNDC7/9 genes with upregulation of the tumor-promoting genes, specifically mTORC1, E2F targets, and Myc targets. On the other hand, elevated expressions of TXNIP and TXNDC11 genes were correlated with suppression of the above tumor-promoting genes. CONCLUSIONS: TXN system and TXNDC family gene panel obtained from the resected tissue of the HCC patients could be used to predict survival prognosis of HCC, and these genes could be considered as potential therapeutic targets for improving HCC survival.

Smart device usage in early childhood is differentially associated with fine motor and language development.

AIM: We evaluated the relationships between the use of smart devices, such as smartphones and tablet computers, and the development levels and language scores in young children. METHODS: A cross-sectional analysis with 117 children aged three to five years was conducted. The participants were recruited from kindergartens in South Korea between November 2015 and April 2016. Parental questionnaires to assess smart device usage status by children, developmental screening test and receptive-expressive language scale were administered; metrics included smart device usage frequency and usage time, appropriate smart device usage level, developmental levels and language scores. RESULTS: Smart device usage frequency was significantly positively correlated with fine motor skill development [Spearman's correlation coefficient (rs ) = 0.426] in three-year-old children. Appropriate smart device usage level was also positively correlated with social development (rs  = 0.466). However, smart device usage time was significantly negatively correlated with expressive language months (rs  = -0.481). There were no such correlations in children aged four to five years. For the subcategories of appropriate usage level, the suitability of social relationship was significantly positively correlated with social development in three-year-old children (rs  = 0.474). CONCLUSION: In three-year-old children, smart device usage was positively correlated with fine motor development and negatively correlated with language development.

Expression of NOX Family Genes and Their Clinical Significance in Colorectal Cancer.

BACKGROUND: The NADPH oxidase (NOX) family is overexpressed in many cancers and is associated with cancer cell proliferation and metastasis; however, little is known about the role of the NOX family in colorectal cancer (CRC). AIMS: To identify the expression of the NOX family in CRC and to investigate the relationship between the expression of NOXs with the prognosis of the patients. METHODS: In the TCGA data portal, mRNA expression data were obtained from 41 normal samples and 458 CRC samples to analyze mRNA expression and gene alteration. We compared the survival differences according to the degree of expression of NOX family in CRC patients and performed Gene Set Enrichment Analysis (GSEA). RESULTS: The mRNA expression of NOX1, 3, 4, and DUOX1, 2 was significantly increased in the colorectal adenocarcinoma. Especially, the higher T and N stage, the more NOX4 expression was significantly increased. Survival analyses showed that NOX4 and NOX5 were associated with poor prognosis; however, NOX1 and DUOX2 were significantly associated with better prognosis. In the results of GSEA of CRC patients, the NOX4 gene was significantly associated with Angiogenesis, EMT and notch signaling. CONCLUSIONS: The NOX family is overexpressed in CRC and is associated with the prognosis of the patient. Therefore, NOX family can predict CRC patient survival and the role of the NOX family as a molecular target in the treatment of CRC.

Hippo effector YAP directly regulates the expression of PD-L1 transcripts in EGFR-TKI-resistant lung adenocarcinoma.

Developments of EGFR-TKI and immunotherapy targeting the PD1/PD-L1 pathway are considered most important medical breakthroughs in lung cancer treatment. Nowadays, 3rd generation EGFR TKI is widely used for T790M positive 1st and 2nd EGFR-TKI resistant lung cancer patients. Immunotherapy is powerful option for lung cancer patients without drug targets and chemotherapy resistant patients. It also has changed the concept of conventional anti-cancer therapy in the point of regulating tumor microenvironment. There are many studies linking these two important pathways. Recent studies demonstrated that PD-L1 expression is significantly correlated to the mutation status of EGFR, and activation of EGFR signaling can also induce the expression of PD-L1. However, the real linker between PD-L1 and EGFR signaling remains to be revealed. Our previous study revealed that the Hippo pathway effector YAP confers EGFR-TKI resistance in lung adenocarcinoma, and inhibition of YAP restores sensitivity to EGFR-TKIs. Thus, we examined whether PD-L1 is relevant, in terms of conferring EGFR-TKI resistance and whether YAP directly regulates the expression of PD-L1 in this context. First, we compared the expression levels of PD-L1 and YAP between EGFR-TKI-resistant PC9 cells and the parental PC9 adenocarcinoma cells. The expression levels of both YAP and PD-L1 were markedly higher in the EGFR-TKI-resistant cells compared to the parental cells, suggesting differential expression pattern between two cell types. YAP knockdown significantly decreased the expression of PD-L1 in the EGFR-TKI-resistant cells, while YAP overexpression increased the expression of PD-L1 in the parental PC9 cells. Then, our results revealed that YAP regulates the transcription of PD-L1, and the YAP/TEAD complex binds to the PD-L1 promoter. Surprisingly, knockdown of PD-L1 was sufficient to decrease cell proliferation and wound healing in the EGFR-TKI-resistant PC9 cells. These data suggest a PD1-independent oncogenic function of PD-L1. The Hippo effector YAP plays a crucial role in linking the PD-L1 and EGFR-TKI resistance by directly regulating the expression of PD-L1 in lung cancer. Targeting PD-L1 directly or via YAP could provide an effective therapeutic strategy for EGFR-TKI-resistant lung adenocarcinoma.

Plasmonic metasurface for simultaneous detection of polarization and spectrum.

We present a new plasmonic metasurface for simultaneous detection of polarization and spectrum of incident light. The demonstrated metasurface is a rationally designed cluster of artificial atoms that are engineered to exhibit polarization and wavelength-selective optical transmission. The fundamental building block of this structure is periodically coupled subwavelength aperture arrays with different orientations and lattice constants. When integrated with pixelated photodetectors, the metasurface can be used to measure the polarization and spectral information of an optical input. In this Letter, simultaneous detection of the polarization and spectrum of polarized light was experimentally demonstrated by analyzing the transmitted intensity distribution through the metasurface. The demonstrated metasurface offers great potential for many applications, such as polarimetric multispectral imaging and polarization-division multiplexing in optical communications.

Complex index of refraction estimation from degree of polarization with diffuse scattering consideration.

The estimation of the refractive index from optical scattering off a target's surface is an important task for remote sensing applications. Optical polarimetry is an approach that shows promise for refractive index estimation. However, this estimation often relies on polarimetric models that are limited to specular targets involving single surface scattering. Here, an analytic model is developed for the degree of polarization (DOP) associated with reflection from a rough surface that includes the effect of diffuse scattering. A multiplicative factor is derived to account for the diffuse component and evaluation of the model indicates that diffuse scattering can significantly affect the DOP values. The scattering model is used in a new approach for refractive index estimation from a series of DOP values that involves jointly estimating n, k, and ρ(d)with a nonlinear equation solver. The approach is shown to work well with simulation data and additive noise. When applied to laboratory-measured DOP values, the approach produces significantly improved index estimation results relative to reference values.

The Solute Carrier (SLC) Transporter Superfamily as Therapeutic Targets for the Treatment of Head and Neck Squamous Cell Carcinoma.

Background: Head and neck squamous cell carcinoma (HNSC) is the most prevalent cancer in the head and neck region, originating from the mucosal epithelium of the oral cavity, pharynx, and larynx. The solute carrier (SLC) transporter superfamily, consisting of over 400 proteins across 65 families, plays a crucial role in cellular functions and presents promising targets in precision oncology. This study aims to analyze the expression of SLC transporters in HNSC and their potential as biomarkers and therapeutic targets. Methods: We leveraged mRNA and protein expression data from The Cancer Genome Atlas (TCGA) and The Human Protein Atlas (HPA) to examine SLC transporter expression in HNSC. Gene Set Enrichment Analysis (GSEA) was conducted to assess the involvement of SLC transporters in various oncogenic pathways. Results: Significant upregulation of SLC transporters was observed in tumor tissues compared to normal tissues, with notable increases in SLC16A3, SLC53A1, SLC25A32, and SLC2A3. This upregulation correlated with poorer overall survival (OS) and disease-specific survival (DSS). GSEA revealed that these transporters are significantly involved in critical oncogenic pathways, including epithelial-mesenchymal transition (EMT), angiogenesis, and hypoxia, which are vital for cancer progression and metastasis. Conclusions: The study identifies SLC transporters as potential biomarkers and therapeutic targets in HNSC. Targeting these transporters with small molecule inhibitors could disrupt essential supply routes for cancer cells, enhancing treatment efficacy and improving patient outcomes. This study paves the way for developing SLC-based target therapies in precision oncology, with the goal of improving survival rates for patients with HNSC.

Defect-assisted plasmonic crystal sensor.

We demonstrate enhanced sensitivity of a nanostructured plasmonic sensor that utilizes resonance in intentional structural defects within a plasmonic crystal. The measured sensitivity of the fabricated nanosensor is ~500 nm/RIU showing improvement over traditional nanohole array sensors. Furthermore, the defects provide an additional design parameter to increase sensitivity by engineering plasmon lifetime.

ATG9B Is a Poor Prognostic Marker Associated With Immune Evasion in Colon Adenocarcinoma.

BACKGROUND/AIM: Autophagy-related genes (ATGs) are involved in autophagy activation, which has a pleiotropic role in cancer development. However, the potential value of ATG expression levels in colon adenocarcinoma (COAD) is unclear. This study aimed to examine the modulation of ATG expression levels and their association with clinical and molecular aspects of COAD. MATERIALS AND METHODS: We used the clinical and molecular phenotypes and RNA sequencing datasets of the cancer genome atlas (TCGA)-COAD project using TCGAbiolinks and cBioPortal. Comparisons of ATG expression levels between tumor and normal tissues were performed using DESeq2 within R. Gene expression and immune cell infiltration levels were analyzed by TIMER. RESULTS: ATG9B had the highest expression levels among ATGs in COAD tissues compared to normal tissues and was related to advanced stage and poor prognosis in COAD. In addition, ATG9B expression was positively associated with the consensus molecular subtype 4 and chromosomal instability but negatively correlated with tumor mutation burden. Furthermore, high ATG9B expression levels were associated with low immune cell infiltration and decreased expression of natural killer cell activation genes. CONCLUSION: ATG9B is a poor prognostic biomarker driving immune evasion of COAD through negative correlation with immune cell infiltration.

A periodically coupled plasmon nanostructure for refractive index sensing.

We present unique characteristics of subwavelength surface plasmon polaritons in a periodically coupled nanowell structure. The nanowell structure offers high quality internal surface plasmon resonance for sensing applications. Calculated FWHM of the transmission peak is 6 nm and the optical transmission is close to 100% at the resonant wavelength of 815.8 nm. The highly concentrated polaritons in the nanowell are sensitive to surface changes providing a sensitivity of 4800% RIU(-1) for optical sensing applications.

Targeting YAP-p62 signaling axis suppresses the EGFR-TKI-resistant lung adenocarcinoma.

BACKGROUND: Despite the progress of advanced target therapeutic agents and immune checkpoint inhibitors, EGFR-TKI resistance is still one of the biggest obstacles in treating lung cancer. Clinical studies with autophagy inhibitors are actively underway to overcome drug resistance. METHODS: We used PC9, PC9/GR, and HCC827/GR cell lines to evaluate the activation of autophagy and EGFR-TKI resistance. Chloroquine was applied as an autophagic blocker and verteporfin was utilized as a YAP inhibitor. RESULTS: In this study, we tried to reveal the effect of autophagy adaptor p62 which is accumulated by autophagy inhibitor in EGFR-TKI-resistant lung adenocarcinoma. We identified that p62 has oncogenic functions that induce cell proliferation and invasion of EGFR-TKI-resistant lung adenocarcinoma. Interestingly, we found for the first time that YAP regulates p62 transcription through ERK, and YAP inhibition can suppress the expression of oncogenic p62. We also confirmed that the expressions of p62 and YAP have a positive correlation in EGFR-mutant lung adenocarcinoma patients. To block cell survival via perturbing YAP-p62 axis, we treated EGFR-TKI-resistant lung cancer cells with YAP inhibitor verteporfin. Remarkably, verteporfin effectively caused the death of EGFR-TKI-resistant lung cancer cells by decreasing the expressions of p62 with oncogenic function, YAP, and its target PD-L1. So, the cumulative effect of oncogenic p62 should be considered when using autophagy inhibitors, especially drugs that act at the last stage of autophagy such as chloroquine and bafilomycin A1. CONCLUSION: Finally, we suggest that targeting YAP-p62 signaling axis can be useful to suppress the EGFR-TKI-resistant lung cancer. Therefore, drug repurposing of verteporfin for lung cancer treatment may be valuable to consider because it can inhibit critical targets: p62, YAP, and PD-L1 at the same time.

Long-Term Mosquito culture with SkitoSnack, an artificial blood meal replacement.

The reliance on blood is a limiting factor for mass rearing of mosquitoes for Sterile-Insect-Technique (SIT) and other mosquito-based control strategies. To solve this problem, we have developed SkitoSnack, a formulated diet for Aedes aegypti (L) mosquitoes, as an alternative for vertebrate blood. Here we addressed the question if long-term yellow fever mosquito culture with SkitoSnack resulted in changed life history traits and fitness of the offspring compared to blood-raised mosquitoes. We also explored if SkitoSnack is suitable to raise Asian tiger mosquitos, Aedes albopictus (L.), and the human bed bug, Cimex lectularius (L). We measured life history traits for 30th generation SkitoSnack-raised Ae. aegypti and 11th generation SkitoSnack-raised Ae. albopictus, and compared them with control mosquitoes raised on blood only. We compared meal preference, flight performance, and reproductive fitness in Ae. aegypti raised on SkitoSnack or blood. We also offered SkitoSnack to bed bug nymphs. We found that long-term culture with SkitoSnack resulted in mosquitoes with similar life history traits compared to bovine blood-raised mosquitoes in both species we studied. Also, Ae. aegypti mosquitoes raised on SkitoSnack had similar flight performance compared to blood raised mosquitoes, were still strongly attracted by human smell and had equal mating success. Minimal feeding occurred in bed bugs. Our results suggest that long-term culture with the blood-meal replacement SkitoSnack results in healthy, fit mosquitoes. Therefore, artificial diets like SkitoSnack can be considered as a viable alternative for vertebrate blood in laboratory mosquito culture as well as for mosquito mass production for Sterile-Insect-Technique mosquito control interventions. SkitoSnack was not suitable to induce engorgement of bed bugs.

TEAD2 as a novel prognostic factor for hepatocellular carcinoma.

TEA Domain Transcription Factors (TEADs) are important in development and serve essential roles in tumorigenesis; however, the role of TEAD2 expression in hepatocellular carcinoma (HCC) has not been widely examined. The present study was conducted to investigate the expression status of TEAD2 in HCC and to evaluate whether the expression of TEAD2 is associated with the prognosis of patients with HCC. mRNA expression data was retrieved for Hippo pathway genes of 50 normal control and 377 HCC samples from The Cancer Genome Atlas data portal. Gene set enrichment, GeneNeighbors, ClassNeighbors and survival analyses were then performed based on the gene expression levels. The mRNA expression of TEAD2 and VGLL4 was significantly higher in HCC compared with the normal control samples, and the mRNA expression of TEAD2 was higher in advanced stages than in early stages. Specifically, survival analysis revealed that higher mRNA expression of TEAD2 was significantly associated with a less favorable overall survival rate (P=0.0067) and there was a trend towards significance between higher mRNA expression of VGLL4 and poor overall survival rate (P=0.051). According to the gene set enrichment analysis, patients with higher mRNA expression of TEAD2 and VGLL4 had strongly enhanced epithelial­mesenchymal transition and angiogenesis, which are associated with tumor progression. In conclusion, increased mRNA expression of TEAD2 is associated with a poor prognosis in patients with HCC. TEAD2 may serve as a prognostic factor for HCC and a novel therapeutic target.

Chip-scale hybrid optical sensing systems using digital signal processing.

We propose a novel hybrid optical sensing system for standalone, chip-scale sensing applications. The hybrid optical sensing system detects any spectral shift of the microresonator sensor output by estimating the effective refractive index using maximum likelihood estimation. The performance evaluation of the proposed hybrid sensing system in the Gaussian-noise dominant environment shows excellent estimation accuracy. This innovative approach allows fully functional integrated hybrid sensing systems, offering great potential in various chip-scale sensing applications.

Integrative analysis of KIF4A, 9, 18A, and 23 and their clinical significance in low-grade glioma and glioblastoma.

To determine the prognostic significance of kinesin superfamily gene (KIF) expression in patients with brain cancer, including low-grade glioma (LGG) and glioblastoma (GBM), we comprehensively analyzed KIFs in 515 LGG and 595 GBM patients. Among KIFs, KIF4A, 9, 18A, and 23 showed significant clinical implications in both LGG and GBM. The mRNA and protein expression levels of KIF4A, 9, 18A, and 23 were significantly increased in LGG and GBM compared with those in the normal control groups. The mRNA expression levels of KIF4A, 9, 18A, and 23 in LGG were significantly increased in the high-histologic-grade group compared with those with a low histologic grade. Genomic analysis showed that the percent of mRNA upregulation of KIF4A, 9, 18A, and 23 was higher than that of other gene alterations, including gene amplification, deep deletion, and missense mutation. In addition, LGG patients with KIF4A, 18A, and 23 gene alterations were significantly associated with a poor prognosis. In survival analysis, the group with high expression of KIF4A, 9, 18A, and 23 mRNA was significantly associated with a poor prognosis in both LGG and GBM patients. Gene Set Enrichment Analysis (GSEA) revealed that high mRNA expression of KIF4A, 18A, and 23 in LGG and GBM patients showed significant positive correlations with the cell cycle, E2F targets, G2M checkpoint, Myc target, and mitotic spindle. By contrast, high mRNA expression of KIF9 in both LGG and GBM patients was significantly negatively correlated with the cell cycle, G2M checkpoint, and mitotic spindle pathway. However, it was significantly positively correlated with EMT and angiogenesis. This study has extended our knowledge of KIF4A, 9, 18A, and 23 in LGG and GBM and shed light on their clinical relevance, which should help to improve the treatment and prognosis of LGG and GBM.

Spatially and spectrally resolved orbital angular momentum interactions in plasmonic vortex generators.

Understanding the near-field electromagnetic interactions that produce optical orbital angular momentum (OAM) is crucial for integrating twisted light into nanotechnology. Here, we examine the cathodoluminescence (CL) of plasmonic vortices carrying OAM generated in spiral nanostructures. The nanospiral geometry defines a photonic local density of states that is sampled by the electron probe in a scanning transmission electron microscope (STEM), thus accessing the optical response of the plasmonic vortex with high spatial and spectral resolution. We map the full spectral dispersion of the plasmonic vortex in spiral structures designed to yield increasing topological charge. Additionally, we fabricate nested nanospirals and demonstrate that OAM from one nanospiral can be coupled to the nested nanospiral, resulting in enhanced luminescence in concentric spirals of like handedness with respect to concentric spirals of opposite handedness. The results illustrate the potential for generating and coupling plasmonic vortices in chiral nanostructures for sensitive detection and manipulation of optical OAM.