Using and engineering amyloid as nanomaterials are blossoming trends in bionanotechnology. Here, we show our discovery of an amyloid structure, termed "amyloid-like nanosheet," formed by a key amyloid-forming segment of Alzheimer's Aβ. Combining multiple biophysical and computational approaches, we proposed a structural model for the nanosheet that is formed by stacking the amyloid fibril spines perpendicular to the fibril axis. We further used the nanosheet for laboratorial retroviral transduction enhancement and directly visualized the presence of virus on the nanosheet surface by electron microscopy. Furthermore, based on our structural model, we designed nanosheet-forming peptides with different functionalities, elucidating the potential of rational design for amyloid-based materials with novel architecture and function.functional amyloid material | peptide self-assembly | nanosheet | retrovirus transduction | beta-amyloid N umerous proteins and polypeptides have been found to selfassemble into amyloid fibrils under certain conditions (1). They are associated not only with dozens of devastating diseases including Alzheimer's and Parkinson's diseases (2) but are integral to many biological processes such as hormone storage, signal transduction, and cell surface adhesion (3-5). Separate from the context of their parent proteins, synthesized peptide segments can self-assemble into amyloid-like fibrils in vitro as well (6, 7). Fibrils formed by diverse proteins and peptides all share a common cross-β structure, composed of interdigitated β-sheets termed "the zipper-like fibril spine" (8, 9). The self-assembly process is a consequence of backbone hydrogen bonding for the single β-sheet layer formation and side-chain interaction (e.g., hydrophobic interaction, π-stacking, and van der Waals) for pairing β-sheet layers together (10). Their highly repetitive and ordered architecture, in particular for the short peptide fibrils, exhibits favorable properties including high thermal stability and stiffness, biocompatibility, controllable self-assembly, surface patterning and integration of functionality, and inexpensive production by chemical synthesis (11-13). These exceptional properties promote the exploitation of amyloid fibril as an emerging class of bionanomaterials (14).Several studies have demonstrated that natural amyloidogenic and designed amphiphilic peptides are capable of self-assembling into nanostructures with topographies including fibril, film, nanotube, hydrogel, and liquid crystals (15-21), and these nanostructures have been used for nanowires, biosensors, 3D culturing, environmental carbon capture, retroviral gene transfer, light harvesting, and catalysis (22-26). Amyloid fibrils were also hybridized with other nanomaterials such as graphene and DNA origami in hopes of creating new properties and functions (27)(28)(29). In this study, we expand the amyloid material field's scope by the finding, structure characterization, and functionalization of a previously unidentified architecture-the amyloid-lik...

Estrogen classically drives lung cancer development via estrogen receptor β (ERβ). However, fulvestrant, an anti-estrogen-based endocrine therapeutic treatment, shows limited effects for non-small cell lung cancer (NSCLC) in phase II clinical trials. G protein-coupled estrogen receptor (GPER), a third estrogen receptor that binds to estrogen, has been found to be activated by fulvestrant, stimulating the progression of breast, endometrial, and ovarian cancers. We here demonstrated that cytoplasm-GPER (cGPER) (80.49 %) and nucleus-GPER (53.05 %) were detected by immunohistochemical analysis in NSCLC samples. cGPER expression was related to stages IIIA-IV, lymph node metastasis, and poorly differentiated NSCLC. Selective agonist G1 and 17β-estradiol (E2) promoted the GPER-mediated proliferation, invasion, and migration of NSCLC cells. Additionally, in vitro administration of E2 and G1 increased the number of tumor nodules, tumor grade, and tumor index in a urethane-induced adenocarcinoma model. Importantly, the pro-tumorigenic effects of GPER induced by E2 were significantly reduced by co-administering the GPER inhibitor G15 and the ERβ inhibitor fulvestrant, as compared to administering fulvestrant alone both in vitro and in vivo. Moreover, the phosphorylation of MAPK and Akt was involved in E2/G1-induced GPER activation. In conclusion, our results indicated that a pro-tumor function of GPER exists that mediated E2-/G1-dependent NSCLC progression and showed better efficiency regarding the co-targeting of GPER and ERβ, providing a rationale for further investigation of anti-estrogen clinical therapy.

G-protein-coupled estrogen receptor (GPER) was found to promote non-small cell lung cancer (NSCLC) by estrogen, indicating the potential necessity of inhibiting GPER by a selective antagonist. This study was performed to elucidate the function of GPER-selective inhibitor G15 in NSCLC development. Cytoplasmic GPER (cGPER) and nuclear GPER (nGPER) were detected by immunohistochemical analysis in NSCLC samples. The relation of GPER and estrogen receptor β (ERβ) expression and correlation between GPER, ERβ, and clinical factors were analyzed. The effects of activating GPER and function of G15 were analyzed in the proliferation of A549 and H1793 cell lines and development of urethane-induced adenocarcinoma. Overexpression of cGPER and nGPER was detected in 80.49% (120/150) and 52.00% (78/150) of the NSCLC samples. High expression of GPER was related with higher stages, poorer differentiation, and high expression of ERβ. The protein level of GPER in the A549 and H1793 cell lines was increased by treatment with E2, G1 (GPER agonist), or fulvestrant (Ful; ERβ antagonist) and decreased by G15. Administration with G15 reversed the E2- or G1-induced cell growth by inhibiting GPER. In urethane-induced adenocarcinoma mice, the number of tumor nodules and tumor index increased in the E2 or G1 group and decreased by treatment with G15. These findings demonstrate that using G15 to block GPER signaling may be considered as a new therapeutic target in NSCLC.