Although zinc finger E-box binding homeobox 1 (ZEB1) has been identified as a key factor in the regulation of breast cancer differentiation and metastasis, its potential role in modulating tumor chemoresistance has not been fully understood. Here, through the study of specimens from a large cohort of human breast cancer subjects, we showed that patients with tumors that expressed high levels of ZEB1 responded poorly to chemotherapy. Moreover, ZEB1 expression was positively correlated with expression of B-cell lymphoma-extra large (Bcl-xL) and cyclin D1, which are key components of tumor chemoresistant mechanisms. At the molecular level, ectopic expression of ZEB1 impaired the responsiveness of breast cancer cells to genotoxic drug treatment, such as epirubicin (EPI). During this process, ZEB1 transcriptionally activated the expression of ataxia-telangiectasia mutated (ATM) kinase by forming a ZEB1/p300/PCAF complex on its promoter, leading to increased homologous recombination (HR)-mediated DNA damage repair and the clearance of DNA breaks. Using a nude mouse xenograft model, we further confirmed that ectopic expression of ZEB1 decreased breast cancer responsiveness to EPI treatment in vivo. Collectively, our findings suggest that ZEB1 is a crucial determinant of chemotherapeutic resistance in breast cancer.

Zinc finger E-box binding homeobox 1 (Zeb1) has been demonstrated to participate in the acquisition of the properties of cancer stem cells (CSCs). However, it is largely unknown how signals from the tumor microenvironment (TME) contribute to aberrant Zeb1 expression. Here, we show that Zeb1 depletion suppresses stemness, colonization and the phenotypic plasticity of breast cancer. Moreover, we demonstrate that, with direct cell-cell contact, TME-derived endothelial cells provide the Notch ligand Jagged1 (Jag1) to neighboring breast CSCs, leading to Notch1-dependent upregulation of Zeb1. In turn, ectopic Zeb1 in tumor cells increases VEGFA production and reciprocally induces endothelial Jag1 in a paracrine manner. Depletion of Zeb1 disrupts this positive feedback loop in the tumor perivascular niche, which eventually lessens tumor initiation and progression in vivo and in vitro. In this work, we highlight that targeting the angiocrine Jag1-Notch1-Zeb1-VEGFA loop decreases breast cancer aggressiveness and thus enhances the efficacy of antiangiogenic therapy.

The high‐performance unidirectional manipulation of microdroplets is crucial for many vital applications including water collection and bioanalysis. Among several actuation methods (e.g., electric, magnetic, light, and thermal actuation), mechanical vibration is pollution‐free and biocompatible. However, it suffers from limited droplet movement mode, small volume range (VMax/VMin < 3), and low transport velocity (≤11.5 mm s−1) because the droplet motion is a sliding state caused by the vertical vibration on the asymmetric hydrophobic microstructures. Here, an alternative strategy is proposed—horizontal vibration for multimode (rolling, bouncing/reverse bouncing, converging/diffusing, climbing, 90o turning, and sequential transport), large‐volume‐range (VMax/VMin ≈ 100), and high‐speed (≈22.86 mm s−1) unidirectional microdroplet manipulation, which is ascribed to the rolling state on superhydrophobic slant microwall arrays (SMWAs) fabricated by the one‐step femtosecond laser oblique ablation. The unidirectional transport mechanism relies on the variance of viscous resistance induced by the difference of contact area between the microdroplet and the slant microwalls. Furthermore, a circular, curved, and “L”‐shaped SMWA is designed and fabricated for droplet motion with particular paths. Finally, sequential transport of large‐volume‐range droplets and chemical mixing microreaction of water‐based droplets are demonstrated on the SMWA, which demonstrates the great potential in the field of microdroplet manipulation.

Biological rice leaf surfaces show a distinct anisotropic sliding property by means of three-level macrogrooves and micro/nanostructures, and they have many potential applications in biomimetic cell movement control, water transportation, and microfluidic devices. However, fabricating artificial threelevel biosurfaces with a controllable anisotropic sliding property by a simple and effective method remains a challenge. Herein, we report a simple method to prepare hierarchical groove structures (macro and micro/nano) on polydimethylsiloxane (PDMS) films using energy-modulation femtosecond laser scanning. The macrogrooves for anisotropic control were realized by larger-energy (>0.40 J cm À2 ) laser scanning, whereas the micro/nanostructures for superhydrophobic ability were fabricated by smallenergy (0.08 J cm À2 ) laser scanning. The processed surface shows a sliding angle (SA) difference of 6 between the perpendicular and parallel directions, which is comparable to that of the natural rice leaf.To quantitatively investigate the anisotropic wettability, surfaces with a different period (100 to 600 mm) and height (30 to 100 mm) were systematically fabricated by adjusting the scanning space and pulse energy. Finally, the distinct ability of the dynamic water droplet anisotropic sliding and size-constrained fog deposition on the anisotropic biosurfaces was demonstrated. The collection efficiency of water on the anisotropic surface with a rotation of 5 and 10 degrees is four times and eighty times higher than that on an isotropic surface. Fig. 1 Multi-level rice leaf surfaces with anisotropic sliding behavior and fabrication of the rice leaf-like biosurfaces. (a) The upside of rice leaf blades. (b) The top-view SEM image of the rice leaf upper surface. The inset is a magnified image of micropillars with nanostructures. (c) Hierarchical model of the rice leaf. (d) Schematic of the bionic rice leaf using a femtosecond laser. (e) Optical image of the processed PDMS film. (f) Top-view SEM of untreated PDMS. (g) Cross-sectional SEM image of the rice leaf-like wavy grooves. (h) Top-view SEM image of the processed PDMS surface, and the insert is a magnified image of micro-nanostructures.