Bimetallic Porphyrin-Based Metal-Organic Framework as a Superior Photocatalyst for Enhanced Photocatalytic Hydrogen Production.

The meaningful and rational engineering of porphyrin-based catalysts with multimetallic active sites is very attractive toward photocatalytic hydrogen generation from water decomposition. Herein, three metal organic frameworks (MOFs) based on meso-tetrakis(4-carboxylphenyl)porphyrin (TCPP) were successfully constructed under solvothermal conditions. As a novel architectured photocatalyst (triclinic, C48H29N4O10PdYb), Pd/Yb-PMOF manifested diverse metal active sites, suitable bandgap positions, prominent visible light-collecting capacity, excellent carrier transfer efficiency, and obvious synergistic effect between ytterbium and palladium ions. Consequently, such a bimetallic MOF exhibited strengthened photocatalytic hydrogen evolution performance. Concretely, its hydrogen generation efficiency was up to 3196.42 µmol g-1 h-1 with 2 wt % Pt as a cocatalyst under visible light illumination. Our work demonstrates a promising strategy for highly efficient visible-light catalysts based on bimetallic-trimmed porphyrin MOFs.

A pan-cancer analysis revealing the role of LFNG, MFNG and RFNG in tumor prognosis and microenvironment.

BACKGROUND: Fringe is a glycosyltransferase involved in tumor occurrence and metastasis. However, a comprehensive analysis of the Fringe family members lunatic fringe (LFNG), manic fringe (MFNG), radical fringe (RFNG) in human cancers is lacking. METHODS: In this study, we performed a pan-cancer analysis of Fringe family members in 33 cancer types with transcriptomic, genomic, methylation data from The Cancer Genome Atlas (TCGA) project. The correlation between Fringe family member expression and patient overall survival, copy number variation, methylation, Gene Ontology enrichment, and tumor-infiltrating lymphocytes (TILs) was investigated by using multiple databases, such as cBioPortal, Human Protein Atlas, GeneCards, STRING, MSigDB, TISIDB, and TIMER2. In vitro experiments and immunohistochemical assays were performed to validate our findings. RESULTS: High expression levels of LFNG, MFNG, RFNG were closely associated with poor overall survival in multiple cancers, particularly in pancreatic adenocarcinoma (PAAD), uveal melanoma (UVM), and brain lower-grade glioma (LGG). Copy number variation analysis revealed that diploid and gain mutations of LFNG was significantly increased in PAAD and stomach adenocarcinoma (STAD), and significantly associated with the methylation levels in promoter regions. Significant differential genes between high and low expression groups of these Fringe family members were found to be consistently enriched in immune response and T cell activation pathway, extracellular matrix adhesion pathway, RNA splicing and ion transport pathways. Correlation between the abundance of tumor-infiltrating lymphocytes (TILs) and LFNG, MFNG, and RFNG expression showed that high LFNG expression was associated with lower TIL levels, particularly in PAAD. In vitro experiment by using pancreatic cancer PANC1 cells showed that LFNG overexpression promoted cell proliferation and invasion. Immunohistochemical assay in 90 PAAD patients verified the expression level of LFNG and its relationship with the prognosis. CONCLUSIONS: Our study provides a relatively comprehensive understanding of the expression, mutation, copy number, promoter methylation level changes along with prognosis values of LFNG, MFNG, and RFNG in different tumors. High LFNG expression may serve as a poor prognosis molecular marker for PAAD.

FOXQ1 promotes pancreatic cancer cell proliferation, tumor stemness, invasion and metastasis through regulation of LDHA-mediated aerobic glycolysis.

Pancreatic cancer (PC), a gastrointestinal tract malignant tumor, has a poor prognosis due to early metastasis and limited response to chemotherapy. Therefore, identifying novel therapeutic approaches for PC is critical. Epithelial-mesenchymal transition (EMT) is known as the vital progress in PC development, we constructed the EMT-related prognosis model to screen out that FOXQ1 probably involving in the EMT regulation. FOXQ1 has been linked to the malignant process in a number of cancers. However, its function in PC is unknown. In our work, the expression of FOXQ1 was elevated in PC tissues, and a high level of FOXQ1 in PC was linked to patients' poor prognosis. FOXQ1 overexpression promoted aerobic glycolysis and enhanced PC cell proliferation, tumor stemness, invasion, and metastasis. Whereas, FOXQ1 silencing showed the reverse effect. Furthermore, mechanistic studies indicated that FOXQ1 promotes LDHA transcription, and thus modulates aerobic glycolysis to enhance PC cell proliferation, tumor stemness, invasion, and metastasis by increasing LDHA expression. Therefore, these novel data suggest that FOXQ1 may be a possible therapeutic target in PC.

On-demand multiplexed vortex beams for terahertz polarization detection based on metasurfaces.

The manipulation of polarization states is crucial for tailoring light-matter interactions and has great applications in fundamental science. Nevertheless, conventional polarization measurement approaches are extremely challenging to determine the polarization state of incident terahertz (THz) beams. The combination of metasurfaces and inhomogeneous vector vortex beams (VVBs) provides a new solution for integrated polarization-related functional devices. Herein, a general design strategy for spin-multiplexing all-silicon metasurfaces is presented and demonstrated in THz polarization detection. The employment of basic building blocks with a high aspect ratio (AR) imparts a greater degree of freedom for generating vector beams, and those basic blocks are subsequently utilized to explore the visualized polarization state. With the assistance of a THz near-field scanning system, we evaluate the capability of reconstructing the incident polarization state from the longitudinal polarization component multiplexed by vortex beams with tight focusing characteristics. Not only that, we also utilize the polarization with dynamically varying behavior as the illumination method to elucidate the evolution trend of the polarization state under a single snapshot and establish a visualized parametric model. This work paves the way to realize ultra-compact THz polarization detection-related devices for future applications in remote sensing, high-resolution imaging, and communications.

Generalized binary spiral zone plates with a single focus obtained by feedforward neural network.

Traditional spiral zone plates (SZPs) have been widely used to generate optical vortices, but this structure suffers from multiple focuses. To eliminate high-order foci, the current method is to design a binary structure that has a sinusoidal transmittance function along the radial direction. With the rapid development of artificial neural networks, they can provide alternative methods to design novel SZPs with a single focus. In this paper, we first propose the concept of generalized binary spiral zone plates (GBSZPs), and train a feedforward neural network (FNN) to obtain the mapping relationship between the relative intensity of each focus and the structural parameters of GBSZPs. Then the structural parameters of GBSZPs with a single focus were predicted by the trained FNN. It is found by simulations and experiments that the intensities of high-order foci can be as low as 0.2% of the required first order. By analyzing the radial transmittance function, it is found that this structure has a different distribution function from the previous radial sinusoidal function, which reveals that the imperfect radial sinusoidal form also can guide the design of binary zone plates to eliminate high-order foci diffraction. These findings are expected to direct new avenue towards improving the performance of optical image processing and quantum computation.

Ketone Synthesis via Irradiation-Induced Generation of a Persistent Ketyl Radical from Acyl Azolium Salts.

A novel three-component α-acylated difunctionalization of alkenes strategy has been developed on the basis of a direct hydrogen atom transfer (HAT) process of photoinduced acyl azolium salts. With simple irradiation without the catalyst, a variety of olefins can be directly converted into ketone derivatives, including 1,4-dione, ß-silyl ketone, 1,5-dione, etc. Mechanistic investigations indicated that the unique reactivity of the acyl azonium triplet excited state is crucial to the strategy's success.

Loss of function of GATA3 regulates FRA1 and c-FOS to activate EMT and promote mammary tumorigenesis and metastasis.

Basal-like breast cancers (BLBCs) are among the most aggressive cancers, partly due to their enrichment of cancer stem cells (CSCs). Breast CSCs can be generated from luminal-type cancer cells via epithelial-mesenchymal transition (EMT). GATA3 maintains luminal cell fate, and its expression is lost or reduced in BLBCs. However, deletion of Gata3 in mice or cells results in early lethality or proliferative defects. It is unknown how loss-of-function of GATA3 regulates EMT and CSCs in breast cancer. We report here that haploid loss of Gata3 in mice lacking p18Ink4c, a cell cycle inhibitor, up-regulates Fra1, an AP-1 family protein that promotes mesenchymal traits, and downregulates c-Fos, another AP-1 family protein that maintains epithelial fate, leading to activation of EMT and promotion of mammary tumor initiation and metastasis. Depletion of Gata3 in luminal tumor cells similarly regulates Fra1 and c-Fos in activation of EMT. GATA3 binds to FOSL1 (encoding FRA1) and FOS (encoding c-FOS) loci to repress FOSL1 and activate FOS transcription. Deletion of Fra1 or reconstitution of Gata3, but not reconstitution of c-Fos, in Gata3 deficient tumor cells inhibits EMT, preventing tumorigenesis and/or metastasis. In human breast cancers, GATA3 expression is negatively correlated with FRA1 and positively correlated with c-FOS. Low GATA3 and FOS, but high FOSL1, are characteristics of BLBCs. Together, these data provide the first genetic evidence indicating that loss of function of GATA3 in mammary tumor cells activates FOSL1 to promote mesenchymal traits and CSC function, while concurrently repressing FOS to lose epithelial features. We demonstrate that FRA1 is required for the activation of EMT in GATA3 deficient tumorigenesis and metastasis.

3D Lanthanide Neodymium Porphyrin Metal-Organic Framework for Photocatalytic Oxidation of Styrene.

A novel three-dimensional lanthanide porphyrin-based MOF (Nd-PMOFs) was synthesized by using tetracarboxyphenyl porphyrin as the ligand and the lanthanide Nd as the coordination metal. Its specific crystal structure information was obtained by single-crystal diffraction with the space group C2/c and the empirical formula C72H45N6Nd2O15.25. This new Nd porphyrin-based MOF with an organic framework formed by a unique coordination method enables the effective separation of photogenerated electrons and holes under photoluminescence, giving it excellent photocatalytic property which could be verified by the characterization data. The photocatalytic performance was examined by taking tert-butyl hydroperoxide as the oxidant and Nd-PMOFs as the catalyst for photocatalytic oxidation of styrene to benzaldehyde with 91.4% conversion and 81.2% benzaldehyde selectivity under optimal reactions, which surpasses most of the results reported in the literature. Several styrenes with other substituents were screened to explore the general applicability of Nd-PMOF for photocatalysis of styrene, among which Nd-PMOFs also exhibited excellent photocatalytic performance. This work offers the possibility to apply lanthanide organometallic frameworks, which are widely used in fluorescent materials, to photocatalysis. In addition, it also provides a new method for the catalytic generation of benzaldehyde from styrene that is consistent with the needs of modern green development.

All-dielectric terahertz metasurfaces with dual-functional polarization manipulation for orthogonal polarization states.

All-dielectric metasurfaces have led to a surge of activities in the field of polarization converters due to their extremely significant potential in the manipulation of terahertz waves. Herein, a versatile all-dielectric metasurface platform that can realize dual-functional polarization manipulation for the orthogonal states of polarization in the terahertz frequency range is proposed. Furthermore, such metasurface platform exhibits the properties of a full-waveplate for one circularly polarized light, and a quarter-waveplate for the orthogonal circularly polarized light. For experimental demonstrations of strategy verification, several representative metasurfaces consisting of subwavelength-scaled all-silicon elliptical cylinders were designed, fabricated, and characterized to demonstrate the capability of dual-functional polarization manipulation, including bifunctional waveplate, near-field imaging, and focusing. The metasurface platform demonstrated here may provide an alternative perspective for the development of compact, versatile polarization terahertz devices, and the design concept can be extended to other frequency ranges as well.

The Senescence-Related Signature Predicts Prognosis and Characterization of Tumor Microenvironment Infiltration in Pancreatic Cancer.

Background: Senescence is thought to be an imperative effect on the development of cancer. However, few studies pay an attention to the senescence-associated genes in pancreatic cancer (PC). The prognostic value of senescence-related genes (SRGs) and their involvement in tumor microenvironment (TME) in the PC remain obscure. The aim of this research was to investigate the prognostic role of senescence-associated genes and their affection in TME in PC. Methods: The transcriptome and clinical information of PC patients were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Two SRG-mediated molecular clusters were comprehensively identified. In total, data from the 285 PC patients were randomly used to develop a senescence-associated gene signature in the training set and verified in the validation set. Immune microenvironment analysis pertained to senescence-related genes was performed. Results: A SRG_score including five senescence-associated genes was established to separate PC patients into two risk groups. High-risk patients had worse overall survival than low-risk patients. The result of the multivariate Cox regression analysis identified the risk score and stage as independent prognostic factors for PC patients. Receiver operating characteristic curve (ROC) analysis confirmed the credible predictive ability of the nomogram. The area under time-dependent ROC curve (AUC) reached 0.746 at 1 year, 0.781 at 3 years, and 0.868 at 5 years in the training set and 0.653 at 1 year, 0.755 at 3 years, and 0.785 at 5 years in the validation set. Moreover, the SRG_score was associated with TME, tumor mutation burden (TMB), and chemotherapeutic drug sensitivity. Conclusions: This study found that the novel SRG_score could be an independent prognostic target for PC patients. Senescence-associated genes had a vital impact on the immune microenvironment and the treatment of PC patients.

Dual-band giant spin-selective full-dimensional manipulation of graphene-based chiral meta-mirrors for terahertz waves.

The ability to simultaneous achieve circular dichroism (CD) and wavefront manipulation is extremely important for many practical applications, especially for detecting and imaging. However, many of the previously observed weakness chiral features are limited to nanostructures with complex three-dimensional building configurations, single narrow-band response, and no active tunability, which are getting farther and away from the goal of integration and miniaturization. Here, a platform of bi-layer all-graphene meta-mirrors with spin-selective full-dimensional manipulation is proposed to simultaneously achieve giant dual-band CD response and wavefront shaping, based on the principle of the hybridization coupling. By simply controlling the structural variables of the meta-mirror and the characteristic parameters of graphene, that is, the combination of passive and active regulation, the proposed design can selectively manipulate the polarization, amplitude, phase, and working frequency of the incident circularly polarized wave near-independently. As a proof of concept, we used the meta-mirror to design two metasurface arrays with spin-selective properties for dynamic terahertz (THz) wavefront shaping and near-field digital imaging, both of which show a high-performance dynamic tunability. This method could provide additional options for the next-generation intelligent THz communication systems.

Ultra-intense vortex laser generation from a seed laser illuminated axial line-focused spiral zone plate.

Relativistic vortex laser has drawn increasing attention in the laser-plasma community owing to its potential applications in various domains, e.g., generation of energetic charged particles with orbital angular momentum (OAM), high OAM X/γ-ray emission, high harmonics generation, and strong axial magnetic-field production. However, the generation of such relativistic vortex laser is still a challenge to the current laser technology. Using micro-structure targets named axial line-focused spiral zone plate (ALFSZP), we propose a novel scheme for ultra-intense vortex laser generation. In the scheme, a relativistic Gaussian laser pulse irradiates an ALFSZP, and diffracts as it passes through the ALFSZP. Due to the focusing and radial Hilbert transform capabilities of the ALFSZP, the seed laser is converted efficiently to a vortex one which is then well focused in a tunable focal volume. Three-dimensional particle-in-cell simulations indicate that using a seed laser pulse with intensity of 1.3 × 1020 W/cm2, the vortex laser intensity achieved is as high as 1.3 × 1021 W/cm2 with the averaged angular momentum per photon up to 0.73ℏ, promising diverse applications in various fields aforementioned.

All-dielectric metasurface for polarization-selective full-space complex amplitude modulations.

Metasurfaces have exhibited powerful capabilities in the modulation of electromagnetic waves. Here, we demonstrate the polarization-selective full-space complex amplitude modulations of incident electromagnetic waves using all-dielectric metasurfaces. This is done via ingeniously designed subwavelength-scale super-pixels. As a proof of concept, we design two metasurfaces working in transmission and reflection spaces: one generates two independent vortex beams and the other generates two pairs of foci of arbitrary intensity ratios. The proposed full-space complex amplitude modulation provides more choices for the manipulation of electromagnetic waves.

Diatomic terahertz metasurfaces for arbitrary-to-circular polarization conversion.

Polarization control is crucial for tailoring light-matter interactions. Direct manipulation of arbitrarily incident polarized waves could provide more degrees of freedom in the design of integrated and miniaturized terahertz (THz) devices. Metasurfaces with unprecedented wave manipulation capabilities could serve as candidates for fulfilling this requirement. Here, a kind of all-silicon metasurface is demonstrated to realize the conversion of arbitrary incident polarization states to circular polarization states in the THz band through the mutual interference of monolayer achiral meta-atoms. Also, we confirmed that the conversion intensities are controllable using the evolution behavior of arbitrary polarization states defined on the Poincaré sphere. Meta-platforms with circularly polarized incidence experience spin-selective destructive or constructive interference, exhibiting broadband circular dichroism (BCD) in the target frequency range. Based on the versatility of the proposed design, the feasibility of the theoretical derivation has been verified in the experiment process. By introducing the geometric phase principle, the proposed design is demonstrated to be an attractive alternative to achieve chiral wavefront manipulation. This work may provide a promising avenue to replace the cumbersome cascaded optical building blocks with an ultrathin meta-platform, which can be used in chiral spectroscopy, imaging, optical communication, and so on.

Metabolomic profiling and alleviation of oxidative stress of Huangjing Zanyu capsule treating oligoasthenospermia.

Background: The traditional Chinese medicine (TCM) patent medicine Huangjing Zanyu capsule (HJZY capsule) has achieved satisfactory clinical effects in the treatment of oligoasthenospermia (OAS). This study aimed to elucidate the impact of HJZY capsule on the reproductive system, focusing on oxidative stress and metabolism profiling during the intervention, to clarify the therapeutic mechanism of HJZY capsule in treating OAS. Methods: Cyclophosphamide was used to establish OAS model rats. Time-sequence specimen collection was applied to monitor the dynamic development of the pharmacological effect of HJZY capsule. Superoxide dismutase (SOD), glutathione peroxidase (GPX), and malonaldehyde (MDA) were evaluated by biochemistry kits to examine the impact of HJZY capsule on oxidative stress. Non-targeted metabolomics was conducted for urine and testis samples, respectively, to investigate metabolic pathways through which the HJZY capsule takes effect. Results: The HJZY capsule elevated sperm density from 62.1±8.28, passing 68.4±7.52, to 75.9±8.48×106/mL, and sperm motility from 62.0%±3.94%, passing 70.8%±9.72%, to 68.8%±4.37%. Meanwhile, SOD (P<0.05 in week 2) and GPX activity levels of HJZY groups were elevated to a certain degree, respectively, and lipid oxidation was attenuated, as shown by decreased MDA content (P<0.05 in week 2). Metabolomics results showed that the HJZY capsule could modulate pathways including taurine metabolism, purine and pyrimidine metabolism, glycerolipid and glycerophospholipid metabolism, and multiple amino acid metabolisms, among others. The cluster analysis results showed that urinary and testicular metabolomics differed in the strength of discrimination between rats in the OAS model and the HJZY groups. Conclusions: The HJZY capsule exerts a comprehensive effect on OAS through influencing various metabolic pathways. Non-targeted metabolomics provides an effective way for profiling complex TCM prescriptions.

Establishment of a 4-miRNA Prognostic Model for Risk Stratification of Patients With Pancreatic Adenocarcinoma.

Pancreatic adenocarcinomas (PAADs) often remain undiagnosed until later stages, limiting treatment options and leading to poor survival. The lack of robust biomarkers complicates PAAD prognosis, and patient risk stratification remains a major challenge. To address this issue, we established a panel constructed by four miRNAs (miR-4444-2, miR-934, miR-1301 and miR-3655) based on The Cancer Genome Atlas (TCGA) and Human Cancer Metastasis Database (HCMDB) to predicted the prognosis of PAAD patients. Then, a risk prediction model of these four miRNAs was constructed by using Cox regression analysis with the least absolute shrinkage and selection operator (LASSO) regression analysis. This model stratified TCGA PAAD cohort into the low-risk and high-risk groups based on the panel-based risk score, which was significantly associated with 1-, 2-, 3-year OS (AUC=0.836, AUC=0.844, AUC=0.952, respectively). The nomogram was then established with a robust performance signature for predicting prognosis compared to clinical characteristics of pancreatic cancer (PC) patients, including age, gender and clinical stage. Moreover, two GSE data were validated the expressions of 4 miRNAs with prognosis/survival outcome in PC. In the external clinical sample validation, the high-risk group with the upregulated expressions of miR-934/miR-4444-2 and downregulated expressions of miR-1301/miR-3655 were indicated a poor prognosis. Furthermore, the cell counting kit-8 (CCK-8) assay, clone formation, transwell and wound healing assay also confirmed the promoting effect of miR-934/miR-4444-2 and the inhibiting effect of miR-1301/miR-3655 in PC cell proliferation and migration. Taken together, we identified a new 4-miRNA risk stratification model could be used in predicting prognosis in PAAD.

Loss of function of GATA3 induces basal-like mammary tumors.

Purpose: GATA3 is a transcription factor essential for mammary luminal epithelial cell differentiation. Expression of GATA3 is absent or significantly reduced in basal-like breast cancers. Gata3 loss-of-function impairs cell proliferation, making it difficult to investigate the role of GATA3 deficiency in vivo. We previously demonstrated that CDK inhibitor p18INK4c (p18) is a downstream target of GATA3 and restrains mammary epithelial cell proliferation and tumorigenesis. Whether and how loss-of-function of GATA3 results in basal-like breast cancers remains elusive. Methods: We generated mutant mouse strains with heterozygous germline deletion of Gata3 in p18 deficient backgrounds and developed a Gata3 depleted mammary tumor model system to determine the role of Gata3 loss in controlling cell proliferation and aberrant differentiation in mammary tumor development and progression. Results: Haploid loss of Gata3 reduced mammary epithelial cell proliferation with induction of p18, impaired luminal differentiation, and promoted basal differentiation in mammary glands. p18 deficiency induced luminal type mammary tumors and rescued the proliferative defect caused by haploid loss of Gata3. Haploid loss of Gata3 accelerated p18 deficient mammary tumor development and changed the properties of these tumors, resulting in their malignant and luminal-to-basal transformation. Expression of Gata3 negatively correlated with basal differentiation markers in MMTV-PyMT mammary tumor cells. Depletion of Gata3 in luminal tumor cells also reduced cell proliferation with induction of p18 and promoted basal differentiation. We confirmed that expression of GATA3 and basal markers are inversely correlated in human basal-like breast cancers. Conclusions: This study provides the first genetic evidence demonstrating that loss-of-function of GATA3 directly induces basal-like breast cancer. Our finding suggests that basal-like breast cancer may also originate from luminal type cancer.

Lossless dielectric metasurface with giant intrinsic chirality for terahertz wave.

It is difficult for single-layer metal metasurfaces to excite in-plane component of magnetic dipole moment, so achieving giant intrinsic optical chirality remains challenging. Fortunately, displacement current in dielectric metasurfaces can form the in-plane magnetic moment which is not orthogonal to the electric dipole moment and forms intrinsic chirality. Here, we show a lossless all-silicon metasurface which achieves giant intrinsic chirality in terahertz band. The leaky waveguide mode in the chiral silicon pillars simultaneously excite the in-plane electric and magnetic dipole moments, which triggers the spin-selected backward electromagnetic radiation, and then realizes the chiral response. The theoretical value of circular dichroism in the transmission spectrum reaches 69.4%, and the measured one is 43%. Based on the photoconductivity effect of the silicon metasurface, we demonstrate optical modulation of the intrinsic chirality using near-infrared continuous wave. In addition, by arranging the two kinds of meta-atoms which are enantiomers, we show the spin-dependent and tunable near-field image display. This simple-prepared all-silicon metasurface provides a new idea for the design of terahertz chiral meta-devices, and it is expected to be applied in the fields of terahertz polarization imaging or spectral detection.

Multifunctional terahertz metasurfaces for polarization transformation and wavefront manipulation.

Conventionally, the realization of polarization transformation and wavefront manipulation in metasurfaces relies on the Pancharatnam-Berry (PB) phase together with the dynamic phase. However, the reported polarization transformation and wavefront manipulation were limited to spin-dependent wavefront manipulation for circular polarization (CP). To obtain more abundant functions, we propose a novel technology that relies on the dynamic phase with a spatial interleaving unit arrangement. With the functions of a quarter wave plate, the metasurfaces we designed can achieve multiple wavefront manipulations which are not only for the spin polarization transformation but also for the linear polarization transformation. Specifically, we design a bifocal metasurface, which can focus on one circularly polarized component as a point and spin-opposite component as a vortex under the linearly polarized (LP) incidence. With the further adjustment of the unit arrangement, the left-hand circularly polarized (LCP) and right-hand circularly polarized (RCP) components under the LP incidence can be refocused on the same point and then composited, resulting in a new LP exit wave. Furthermore, we prove theoretically that the desired x-LP component and y-LP component under the arbitrary CP incidence can also be manipulated independently. We believe that the versatility of this method will provide a novel platform for the development of terahertz integrated photonics.

GATA3 functions downstream of BRCA1 to suppress EMT in breast cancer.

Purpose: Functional loss of BRCA1 is associated with poorly differentiated and metastatic breast cancers that are enriched with cancer stem cells (CSCs). CSCs can be generated from carcinoma cells through an epithelial-mesenchymal transition (EMT) program. We and others have previously demonstrated that BRCA1 suppresses EMT and regulates the expression of multiple EMT-related transcription factors. However, the downstream mediators of BRCA1 function in EMT suppression remain elusive. Methods: Depletion of BRCA1 or GATA3 activates p18INK4C , a cell cycle inhibitor which inhibits mammary epithelial cell proliferation. We have therefore created genetically engineered mice with Brca1 or Gata3 loss in addition to deletion of p18INK4C , to rescue proliferative defects caused by deficiency of Brca1 or Gata3. By using these mutant mice along with human BRCA1 deficient as well as proficient breast cancer tissues and cells, we investigated and compared the role of Brca1 and Gata3 loss in the activation of EMT in breast cancers. Results: We discovered that BRCA1 and GATA3 expressions were positively correlated in human breast cancer. Depletion of BRCA1 stimulated methylation of GATA3 promoter thereby repressing GATA3 transcription. We developed Brca1 and Gata3 deficient mouse system. We found that Gata3 deficiency in mice induced poorly-differentiated mammary tumors with the activation of EMT and promoted tumor initiating and metastatic potential. Gata3 deficient mammary tumors phenocopied Brca1 deficient tumors in the induction of EMT under the same genetic background. Reconstitution of Gata3 in Brca1-deficient tumor cells activated mesenchymal-epithelial transition, suppressing tumor initiation and metastasis. Conclusions: Our finding, for the first time, demonstrates that GATA3 functions downstream of BRCA1 to suppress EMT in controlling mammary tumorigenesis and metastasis.