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Estrogen receptors (ER␣ and ER␤) are ligand-regulated transcription factors that play critical roles in the development and progression of breast cancer by regulating target genes involved in cellular proliferation. The transcriptional activity of ER␣ and ER␤ is known to be modulated by cofactor proteins. We used a yeast twohybrid system and identified NFAT3 as a novel ER␤-binding protein. NFAT3 interacted with ER␣ and ER␤ both in vitro and in mammalian cells in a ligand-independent fashion. NFAT3 bound specifically to the ER␤ region containing the activation function-1 domain, a ligand-independent transactivation domain. Overexpression of NFAT3 enhanced both ER␣ and ER␤ transcriptional activities in a ligand-independent manner and up-regulated downstream estrogen-responsive genes including pS2 and cathepsin D. Reduction of endogenous NFAT3 with NFAT3 small interfering RNA or overexpression of NFAT3 deletion mutants that lack the ER-binding sites reduced the NFAT3 coactivation of ER␣ and ER␤. NFAT3 increased binding of ER␣ to the estrogen-responsive element and was recruited to endogenous estrogen-responsive promoters. NFAT3 was expressed differentially in many breast cancer cell lines and overexpressed in a subset of breast cancer patients. Knockdown of endogenous NFAT3 reduced the growth of human breast cancer ZR75-1 cells in a ligand-independent manner. Taken together, these results suggest that NFAT3 may play important roles in ER signaling and represent a novel target for breast cancer therapy.Estrogen receptors (ER␣ and ER␤) 3 are members of the steroid hormone superfamily of nuclear receptors that act as ligand-activated transcription factors (1-3). Both of the two receptors regulate gene transcription either by binding directly to estrogen-responsive elements (ERE) located within the promoter regions of target genes or interacting with other transcription factors such as AP1 and SP1 (4, 5). ER␣ and ER␤ share structural similarity characterized by several functional domains. Two distinct activation function (AF) domains contribute to the transcriptional activity of the two receptors. The first activation function AF-1, a ligand-independent transactivation domain, is located at the N terminus, whereas the second, ligand-dependent activation function, AF-2, is located at the C terminus, overlapping the ligandbinding domain. The AF-1 activity of ER␤ is weak, compared with that of ER␣, whereas their AF-2 activities are similar (6). In most cases, the AF-1 and AF-2 domains interact functionally to enhance transcription in a cooperative manner. The DNA-binding domain (DBD) of the two receptors is centrally located. ER␣ and ER␤ possess similar binding affinities for estrogen and their cognate DNA binding site, which is probably caused by the high degree of sequence homology they share in their ligand and DNA binding domains (7). The ligand binding domain shows 58% homology between ER␣ and ER␤. The DNA binding domain is identical between the two receptors except for three amino acids. However, the N terminus co...

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electromagnetic (EM) waves. Numerous interesting physical functions are realized by metamaterials [1][2][3][4][5] such as negative refraction, [1] invisibility cloaks, [2,3] and superlens. [4] Metasurfaces are planer versions of bulk metamaterials to control the EM waves on their phases, [6] amplitudes, [7] and polarizations. [8] Evolved from traditional metamaterials described by effective medium parameters, digital coding metamaterials have been proposed [9] to design metasurfaces from digital perspective and realize programmable functionalities using a single metasurface. In the digital coding metasurfaces, two distinct EM responses can be encoded as digits "1" and "0," [10,11] Then the related metasurface design is transformed into digital process. As a result, some groundbreaking researches like convolution operations [12] and information entropy [13] for metasurfaces have been presented, suggesting potential relations between the digital world and the physical world. Within this perspective, we can not only encode the phase responses, but also other EM characteristics like polarizations and orbital angular momentum (OAM) modes. [14,15] Consequently, the digitally programmable methods bring plentiful functions, such as space-time coding, [16,17] and new-architecture communication system. [18][19][20] As an important concept in microwave and optical frequencies, nonreciprocity has raised in myriad physical branchesthermodynamics, mechanics, electromagnetism, optics, and so on. [21] The classic nonreciprocal devices like circulators are indispensable components in radar [22] and communication systems. [23] For traditional electromagnetics, nonreciprocal devices are predominantly based on magnetized materials, [24,25] like ferrites, usually composed of iron oxides and other elements (Al, Ni, Co). [26] However, these kinds of materials are usually large, bulky, uneconomical, and difficult to integrate into the metasurfaces. To overcome these drawbacks, magnetless nonreciprocial metasurfaces (MNMs) have been proposed. [27][28][29][30][31] By interconnecting transistor-like amplifier [27][28][29] and isolator [30,31] into metasurface structure, MNMs can easily achieve smaller size and better integrability. In addition, nonreciprocial metamaterials based on time modulation have also been presented, [32] but their control system complexity is greatly increased.

Controlling the polarization state of electromagnetic waves is an important topic in microwaves due to the enormous application potential in radar technology and mobile communications. Here, we propose a programmable metasurface based on single-pole double-throw switches to realize multifunctional polarization conversions. A structure of the double-sided metallic pattern is adopted in the metasurface, in which a novel double-pole double-throw hub is achieved to guide the energy direction. Such a mechanism successfully induces multiple transmission channels into the metasurface structure for functional design. By controlling the states of the switches with a field programmable gate array, the x- and y-polarizations of the incident waves can be efficiently modulated into linear co- and cross-polarizations of transmitted waves, suggesting a higher degree of freedom on wave manipulations. The proposed metasurface can be developed as a near-field information encoder to transmit binary coding sequence according to the energy distribution. Character transmissions are realized by programming binary ASCII codes on the transmitted fields. Nine supercells on the metasurface can encode 9-bit binary information in one frame of near-field imaging, which can be switched in real time with high speed. We envision that this work will develop digital coding applications to control the polarization information.