MNDA expression and its value in differential diagnosis of B-cell non-Hodgkin lymphomas: a comprehensive analysis of a large series of 1293 cases.

AIMS: MNDA (myeloid nuclear differentiation antigen) has been considered as a potential diagnostic marker for marginal zone lymphoma (MZL), but its utility in distinguishing MZL from other B-cell non-Hodgkin lymphomas (B-NHLs) and its clinicopathologic relevance in diffuse large B-cell lymphoma (DLBCL) are ambiguous. We comprehensively investigated MNDA expression in a large series of B-NHLs and evaluated its diagnostic value. METHODS: MNDA expression in a cohort of 1293 cases of B-NHLs and 338  cases of reactive lymphoid hyperplasia (RLH) was determined using immunohistochemistry and compared among different types of B-NHL. The clinicopathologic relevance of MNDA in DLBCL was investigated. RESULTS: MNDA was highly expressed in MZLs (437/663, 65.9%), compared with the confined staining in marginal zone B-cells in RLH; whereas neoplastic cells with plasmacytic differentiation lost MNDA expression. MNDA expression was significantly higher in mantle cell lymphoma (MCL, 79.6%, p = 0.006), whereas lower in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL, 44.8%, p = 0.001) and lymphoplasmacytic lymphoma (LPL, 25%, p = 0.016), and dramatically lower in follicular lymphoma (FL, 5.2%, p < 0.001), compared with MZL. 29.6% (63/213) of DLBCLs were positive for MNDA. The cases in non-GCB group exhibited a higher rate of MNDA positivity (39.8%) compared to those in GCB group (16.3%) (p < 0.001), and MNDA staining was more frequently observed in DLBCLs with BCL2/MYC double-expression (50%) than those without BCL2/MYC double-expression (24.8%) (p = 0.001). Furthermore, there was a significant correlation between MNDA and CD5 expression in DLBCL (p = 0.036). CONCLUSIONS: MNDA was highly expressed in MZL with a potential utility in differential diagnosis between MZL and RLH as well as FL, whereas its value in distinguishing MZL from MCL, CLL/SLL is limited. In addition, MNDA expression in DLBCL was more frequently seen in the non-GCB group and the BCL2/MYC double-expression group, and demonstrated a correlation with CD5, which deserves further investigation. The clinical relevance of MNDA and its correlation with the prognosis of these lymphomas also warrant to be fully elucidated.

[Fuyu Decoction ameliorates myocardial fibrosis in rat model of heart failure by regulating Nrf2/GPX4-mediated ferroptosis].

This study aims to investigate the effect and mechanism of Fuyu Decoction(FYD) in the treatment of myocardial fibrosis in the rat model of heart failure(HF). Sixty Wistar rats were randomized into a modeling group(n=50) and a sham group(n=10). A post-myocardial infarction HF model was established by ligating the left anterior descending coronary artery in rats. The successfully modeled rats were assigned into model, low-dose(2.5 g·kg~(-1)) FYD(FYD-L), high-dose(5.0 g·kg~(-1)) FYD(FYD-H), and FYD+Nrf2 inhibitor(ML385, 30 mg·kg~(-1)) groups(n=10). FYD was administrated by gavage and ML385 by intraperitoneal injection. The rats in the sham and model groups were administrated with equal amounts of normal saline by gavage. After 8 weeks of intervention, the cardiac function indicators were measured, and the myocardial tissue morphology and collagen deposition were observed. The positive expression of collagens Ⅰ and Ⅲ, apoptosis, and oxidative stress were examined, and the levels of Fe~(2+) and reactive oxygen species(ROS) were determined. The protein levels of nuclear factor erythroid 2-related factor 2(Nrf2), solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), and acyl-coenzyme A synthase long chain family member 4(ACSL4) in the myocardial tissue were determined. Compared with sham group, the model group showed decreased left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), increased left ventricular end internal dimension in systole(LVIDs), left ventricular internal diameter in diastole(LVIDd), and myocardial collagen deposition, positive expression of collagens Ⅰ and Ⅲ, elevated apoptosis rate and malondialdehyde(MDA), Fe~(2+), and ROS levels, lowered superoxide dismutase(SOD) and glutathione peroxidase(GSH) levels, down-regulated protein levels of Nrf2, SLC7A11, and GPX4, and up-regulated protein level of ACSL4. Compared with the model group, the above indicators were restored by FYD. Moreover, ML385 reversed the protective effect of FYD on myocardial fibrosis in HF rats. In conclusion, FYD can inhibit ferroptosis by activating the Nrf2/GPX4 pathway, thereby ameliorating myocardial fibrosis in HF rats.

Preparation of Temperature-Responsive Films Based on PNVCL Microgel with Varying Sizes and Cross-Linking Degrees for Cell Harvesting.

This work reports preparing thermal responsive poly (N-isovinylcaprolactam) (PNVCL) microgel based films for cell growth and detachment. PNVCL microgels of hydrated size ranging from 386 to 815 nm (25 °C) and different crosslinking degree are prepared. The PNVCL microgels can be rapidly and massively deposited on glass by spin coating method. Atomic force microscopy (AFM) and water contact angle (WCA) are used to study the influence of crosslinking degree and particle size on the surface morphology, stability, and hydrophilicity of PNVCL microgel film. The cell activity of the desorbed cells is quantitatively characterized employing human normal lung epithelial cells (BEAS-2B). The results show that BEAS-2B cells can be desorbed quickly from the film in 30 min, and the optical density (OD) value of desorbed cells incubated after 3 d increases by approximately 52% compared to the control group. This study broadens the selection of temperature-sensitive film for cell harvesting, and provides a new tool for the quantitative characterization of desorbed cells.

Oridonin loaded peptide nanovesicles alleviate nonalcoholic fatty liver disease in mice.

This study was to construct a nanovesicle delivery system to improve the loading efficiency and stability of ORI for the treatment of nonalcoholic fatty liver disease (NAFLD). This nanovesicles (NVs) exerted a narrow size distribution (195.6 ± 11.49 nm) and high entrapment efficiency (84.46 ± 1.34%). In vitro cell studies demonstrated that the NVs treatment enhanced the cellular uptake of ORI and reduced lipid over-accumulation and total cholesterol levels in NAFLD cell model. At the same time, in vivo study proved that, compared with the normal group, the model group mice showed a decrease in body weight, a significant increase in liver index (6.71 ± 0.62, p < 0.01), and symptoms of liver lipid accumulation, lipid vesicles, and liver tissue fibrosis. Compared with the model group, after high-dose ORI NVs intervention, mice gained weight, decreased liver index (4.69 ± 0.55, p < 0.01), reduced hepatic lipid droplet vacuoles, reduced lipid accumulation (reduced oil red area, p < 0.001), and alleviated the degree of liver fibrosis (reduced blue collagen area, p < 0.001). In conclusion, ORI/HP-ß-CD/H9-HePC NVs showed specific liver accumulation and improved therapeutic effects, the nano drug loading system provides a promising strategy for the encapsulation of ORI to effectively alleviate the process of NAFLD.

Correction: Enhanced DNA release from disulfide-containing layered nanocomplexes by heparin-electrostatic competition.

Correction for 'Enhanced DNA release from disulfide-containing layered nanocomplexes by heparin-electrostatic competition' by Zhenzhen Chen et al., J. Mater. Chem. B, 2015, 3, 225-237, https://doi.org/10.1039/c4tb01113a.

VEGFA/NRP-1/GAPVD1 axis promotes progression and cancer stemness of triple-negative breast cancer by enhancing tumor cell-macrophage crosstalk.

Triple-negative breast cancer (TNBC) has long been considered a major clinical challenge due to its aggressive behavior and poor prognosis. Cancer stem cells (CSCs) are known as the main cells responsible for tumor origination, progression, recurrence and metastasis. Here, we report that M2-type tumor-associated macrophages (TAMs) contribute to cancer stemness in TNBC cells via the secretion of VEGFA. Reciprocally, elevated VEGFA expression by TAM-educated TNBC cells acts as a regulator of macrophage polarization, therefore constitute a feed-back loop between TNBC cells and TAMs. Mechanistically, VEGFA facilitates the CSC phenotype via the NRP-1 receptor and downstream GAPVD1/Wnt/ß-catenin signaling pathway in TNBC cells. Our study underscores the crosstalk between TNBC cells and TAMs mediated by VEGFA and further clarifies the role and underlying mechanisms of the VEGFA/NRP-1/GAPVD1 axis in regulating cancer stemness. We also document an immunosuppressive function of VEGFA in the tumor microenvironment (TME). Therefore, the present study indicates crosstalk between TNBC cells and TAMs induced by VEGFA and provides a potential implication for the combination of immunotherapy and VEGFA-targeted agents in TNBC therapy.

Correlationship between self-assembly behavior and emulsion stabilization of pea protein-high methoxyl pectin complexes treated with ultrasound at pH 2.0.

This study investigated the effects of ultrasound on the self-assembly behavior of pea protein (PP)-high methoxyl pectin (HMP) complexes at pH 2.0 through transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and intrinsic fluorescence analysis. The emulsion stabilization mechanism of PP-HMP treated with ultrasound (PP-HMP-US) was also elucidated. The results indicated that ultrasound increased the emulsifying activity index (EAI) and emulsifying stability index (ESI) of PP-HMP. Moreover, PP-HMP-US-based emulsions formed small, dispersed oil drops, which were stable during storage. PP-HMP- and PP-HMP-US-based emulsions did not demonstrate any creaming. The TEM results revealed that ultrasound can regulate the self-assembly behavior of PP and HMP to form spherical particles with a core-shell structure. This structure possessed low turbidity, a small particle size, and high absolute zeta potential values. The FTIR and intrinsic fluorescence spectra demonstrated that ultrasound increased the α-helix and ß-sheet contents and exposed the tryptophan groups to more hydrophilic environments. Ultrasound also promoted the PP-HMP self-assembly through electrostatic interaction and improved its oil-water interfacial behavior, as indicated by the EAI and ESI values of PP-HMP-US-based emulsions. The current results provide a reference for the development of an innovative emulsifier prepared by ultrasound-treated protein-pectin complexes at low pH.

Second-Generation Soft Actuators Driven by NIR Light Based on Croconaine Dye-Doped Vitrimers.

Soft actuators with photo-response can be selectively driven by the light source, but it is challenging to achieve a selective response of multiple components under a uniform light field, which is actually of great importance for the development of soft robots. In this work, a series of near-infrared light (NIR)-responsive vitrimers (CR-vitrimers) are synthesized by carboxylate transesterification using carboxyl-bearing croconaine dye (CR-800) as a photothermal agent (PTA). NIR-responsive liquid crystalline elastomers (CR-vitrimer-LCEs) under NIR laser (λmax = 808 nm) without the template can be further prepared. More importantly, the dynamic covalent bonding properties of vitrimer allow for the fabrication of a hand-shaped actuator by hot pressing, consisting of "fingers" with different NIR-response threshold values. After programming as needed, the hand-shaped actuator successfully achieves local and sequential control under a uniform NIR light field.

Interaction mechanisms of peanut protein isolate and high methoxyl pectin with ultrasound treatment: The effect of ultrasound parameters, biopolymer ratio, and pH.

Ultrasound could effectively change molecular structure of proteins, polysaccharides, and their interactions, and was used to treat the peanut protein isolate-high methoxy pectin (PPI-HMP) complexes in this study. Effects of different ultrasound parameters, PPI-HMP mixing ratio (40:1-5:2), and pH (2.0-8.0) on the PPI-HMP interactions were investigated. Turbidity, solution appearance, and Zeta-potential analysis revealed an electrostatic interaction between PPI and HMP from pH 2.0 to pH 6.0. Ultrasound changed the tertiary structure conformation of PPI according to the surface hydrophobicity analysis. Increased ultrasound power density and pH broke the hydrogen bonds between the complexes according to Fourier transform infrared spectroscopy analysis. Apparent viscosity and confocal laser scanning microscopy analysis showed that appropriate ultrasound treatment (5.43 W/cm3, 25 min, 25 °C) reduced the viscosity of the complexes, and enhanced the electrostatic and hydrophobic interactions between PPI and HMP. These findings will contribute to the application of PPI-HMP complexes in the food industry.

Buyang huanwu decoction (BYHWD) alleviates sepsis-induced myocardial injury by suppressing local immune cell infiltration and skewing M2-macrophage polarization.

OBJECTIVE: To investigate the therapeutic effect of Buyang huanwu decoction (BYHWD) on sepsis-induced myocardial injury (SIMI) and explore the mechanism by which BYHWD mitigates SIMI. METHODS: The Lipopolysaccharide (LPS)-induced SIMI mouse model was established to detect the effect of BYHWD-low (1 mg/kg), BYHWD-middle (5 mg/kg), and BYWHD-high (20 mg/kg) on SIMI. The survival of these BYHWD-treated septic mice was investigated. The histology of myocardial tissues was determined by hematoxylin and eosin (H&E) staining. The apoptotic index and inflamed microenvironment of myocardial tissues were assessed by immunofluorescent staining (IF) and flow cytometry analysis. Liquid chromatography-mass spectrometry (LC-MS/MS) was employed to determine the key chemical components in the serum of BYHWD-loaded septic mice. Immunoblotting assay was utilized to detect NF-κB and TGF-ß signaling activity, and M1/M2-macrophage markers using RAW264.7 cells. RESULTS: The high dosage of BYHWD (BYHWD-high, 20 mg/Kg) significantly attenuated SIMI and improved the survival of septic mice. The BYHWD-high solution markedly reduced myocardial cell apoptosis and mitigated the inflamed microenvironment by suppressing CD45+ immune cell infiltration. Importantly, BYHWD decreased macrophage accumulation and promoted an M2-macrophage polarization. Paeoniflorin (PF) and calycosin-7-O-ß-glucoside (CBG) were identified as the key molecules in BYWHD with therapeutic effect. PF (10 µM) and CBG (1 µM) inhibited NF-κB signaling, meanwhile they upregulated the TGF-ß pathway, thereby facilitating an M2-macrophage phenotypic transition in RAW264.7 cells. CONCLUSIONS: BYHWD, with two effective components PF and CBG, can mitigate SIMI by suppressing the inflamed myocardial microenvironment and skewing an immunosuppressive M2-macrophage phenotype.

[Correlation between ARID5B Gene SNP and MTX Resistance in Children with ALL].

OBJECTIVE: To investigate the correlation between single-nucleotide polymorphism (SNP) of ARID5B gene and resistance to methotrexate (MTX) in children with acute lymphoblastic leukemia (ALL). METHODS: A total of 144 children with ALL who were treated in General Hospital of Ningxia Medical University from January 2015 to November 2021 were enrolled and divided into MTX resistant group and non-MTX resistant group, with 72 cases in each group. Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) technology was used to measure the SNP of ARID5B gene in all children and analyze its correlation with MTX resistant. RESULTS: There were no significant differences in the genotype and gene frequency of rs7923074, rs10821936, rs6479778, and rs2893881 between MTX resistant group and non-MTX resistant group (P>0.05). The frequency of C/C genotype in the MTX resistant group was significantly higher than that in the non-MTX resistant group, while the frequency of T/T genotype was opposite (P<0.05). The frequency of C allele in the MTX resistant group was significantly higher than that in the non-MTX resistant group, while the frequency of T allele was opposite (P<0.05). Multivariate logistic regression analysis showed that ARID5B gene rs4948488 TT genotype and T allele frequency were risk factors for MTX resistant in ALL children (P<0.05). CONCLUSION: The SNP of ARID5B gene is associated with MTX resistant in ALL children.

The droplet breakup model and characteristics of pH-shifted peanut protein isolate-high methoxyl pectin stabilised emulsions under ultrasound.

The effect of pH on the occurrence states of peanut protein isolate (PPI) and high methoxyl pectin (HMP), and droplet breakup model of the emulsions under ultrasound were studied. Particle size distribution and scanning electron microscopy results showed that PPI-HMP existed a soluble complex at pH 5.0, had no interaction at pH 7.0, and was co-soluble at pH 9.0. Droplet breakup model results revealed that the characteristics of emulsion stabilised by PPI-HMP treated at pH 5.0 was different from that at pH 7.0 and 9.0. The average diameter of the droplet well satisfied the model. According to rheological properties, interface tension, and microstructure, the formation mechanism and characteristics of emulsion stabilised by PPI-HMP treated at pH 5.0 was different from that at pH 7.0 and pH 9.0. The research provided a reference for constructing emulsions using pH-shifted PPI-HMP under ultrasound.

NIR-Photocontrolled Aqueous RAFT Polymerization with Polymerizable Water-Soluble Zinc Phthalocyanine as Photocatalyst.

In order to give an answer for the challenges of long wavelength-photocontrolled radical polymerization in aqueous solutions and to address the shortcomings of conventional near-infrared (NIR) photocatalysts (PCs) that are difficult to subject to post-treatment, we designed and synthesized a series of ß-tetra-substituted water-soluble zinc phthalocyanines (ß-TS-Zns) as the NIR PCs for reversible addition-fragmentation chain transfer (RAFT) polymerization successfully under irradiation with NIR (λmax = 730 nm) light at room temperature. Importantly, the NIR PCs can also be designed as polymerizable monomers and covalently loaded on the polymer chains, which are endowed with permanent NIR photocatalysis of the resultant polymers. Moreover, the polymerization can not only be carried out in water but also in phosphate buffer saline (PBS) solution, yielding polymers with controlled molar mass and narrow dispersities (D = 1.03-1.25). Therefore, this NIR-photocontrolled aqueous RAFT polymerization system may provide a charming strategy for possible applications in tissue engineering biomaterial in situ benefiting from the high penetration ability of NIR light.

The convergence of 2,6-dichloro-1,4-benzoquinone in the whole process of lignin phenol precursor chlorination.

The formation and decomposition of 2,6-dichloro-1,4-benzoquinone, an emerging disinfection byproduct (DBP), was studied in the chlorination of lignin phenol precursors. The results show that DCBQ and the related hydroxyl DCBQ (DCBQ-OH) acts as the intermediate products of the chlorination process of the three typical lignin phenol precursors (p-hydroxybenzoic acid, protocatechuic acid, and gallic acid). The contributions of lignin phenol precursors to the overall formation of the targeted DBPs were determined based on the observed abundances of individual lignin phenols and their DBP yields. DCBQ and DCBQ-OH were generated within 2-6 h, the relative abundance of the yields of mol carbon atoms in DCBQ corresponding to the mol carbon atoms in the three model precursors (DCBQ-C) was about 0.01%-14.37% under different pH conditions. With the chlorination reaction time increased (after two or four h), the concentrations of DCBQ and DCBQ-OH entirely decreased, and the decomposition of DCBQ do not follow a pseudo-first-order kinetics during chlorination. Conversely, the decomposition of DCBQ generated from p-hydroxybenzoic acid followed a pseudo-second-order kinetics. Moreover, the formation of trichloromethane (TCM), dichloroacetic acid (DCAA), and trichloroacetic acid (TCAA) was also detected during the chlorination. The contribution of the decomposed DCBQ was mainly to TCAA and the unknown DBPs within 2-12 h, and DCBQ decomposition pathway was affected by pH. Moreover, except for DCBQ/DCBQ-OH and TCM/HAAs, there were still 73.6%-92.41% unknown products (including non-halogenated aromatic DBPs and chlorine-substituted DBPs) needing to identify during the chlorination process for lignin phenols. Overall, revealing the formation and decomposition of DCBQ during the chlorination of lignin phenol precursors would contribute to the effective development of drinking water treatment processes for the removal of highly toxic intermediates generated during disinfection.

Unimolecular micelles from star-shaped block polymers by photocontrolled BIT-RDRP for PTT/PDT synergistic therapy.

Unimolecular micelles (UIMs) exhibit promising potential in the precise diagnosis and accurate treatment of tumor tissues, a pressing problem in the field of medical treatment, because of their perfect stability in the complex and variable microenvironment. In this study, porphyrin-based four-armed star-shaped block polymers with narrow molar mass dispersity (D = 1.34) were facilely prepared by photocontrolled bromine-iodine transformation reversible-deactivation radical polymerization (BIT-RDRP). A photothermal conversion dye, ketocyanine, was covalently linked onto the PEG and then introduced into the polymers through a "grafting onto" strategy to obtain polymeric nanomaterial, THPP-4PMMA-b-4P(PEGMA-co-APMA)@NIR-800, with dual PTT/PDT function. The resulting polymers could form monodispersed UIMs in the water below critical aggregation concentration, meanwhile maintaining the capacities of singlet oxygen release and photothermal conversion. Importantly, the UIMs displayed excellent biocompatibility while exerting superior PTT and/or PDT therapeutic effects under the irradiation of specific wavelengths of light, according to in vitro cellular experiments, which is expected to become a new hot spot for cancer therapy and anti-tumor research. Overall, stable and powerful UIMs with dual PTT/PDT function is provided, which are expected to be competitive candidates in cancer therapy.

Hierarchical Self-Assembly of Triphilic Main-Chain-Type Semifluorinated Alternating Graft Copolymers in Aqueous Solution.

Fluorinated copolymers can self-assemble in solution and form micelles with rare properties due to the peculiar behavior of fluorinated groups. However, the process description of the self-assembly is still largely phenomenological and difficult to explain due to the tendency of the fluorinated segments to segregate from both the hydrophilic and lipophilic segments, which can result in various morphologies. Herein, the controlled formation of ellipsoidal micelles, disklike micelles, and sheets by hierarchical self-assembly of triphilic main-chain-type semifluorinated alternating graft copolymers (AB)n A-g-mOEG is presented (where A represents unit of α,ω-diiodoperfluoroalkane, B represents the unit of α,ω-unconjugated diene, and mOEG represents methoxy oligo(ethylene glycol)), which are synthesized by step transfer-addition and radical-termination (START) polymerization and azide-alkyne click chemistry. Furthermore, the possible self-assembly mechanism of these micron-level aggregates is proposed, which is ascribed to the hierarchical self-assembly, crowding effect of hydrophilic chains and the interfacial tension between the fluoroalkane and alkane segments. This study can provide a facile and highly efficient approach to the synthesis of main-chain-type fluorinated graft copolymers and expand the research field for the solution self-assembly of fluorinated copolymers.

Suppressing circ_0008494 inhibits HSCs activation by regulating the miR-185-3p/Col1a1 axis.

Background: Hepatic fibrosis (HF) is characterized by activation of hepatic stellate cells (HSCs) and extensive deposition of extracellular matrix components, especially collagens. However, effective antifibrotic therapies are still lacking. Recently, circular RNAs (circRNAs) have been identified as novel regulators of HF. Methods: circRNAs profile was screened by RNA sequencing and the location of circ_0008494 was confirmed by fluorescence in situ hybridization assay in human HF tissues. Bioinformatics analysis was used for result prediction and dual-luciferase reporter, together with AGO-RIP and biotin-coupled miRNA capture assays, were used to determine miR-185-3p/collagen type I alpha 1 chain (Col1a1) as the target of circ_0008494. A stable circ_0008494-interfering human HSCs cell line was constructed and used to determine the regulatory mechanism of circ_0008494/miR-185-3p/Col1a1 axis. Results: circ_0008494 was abundantly and significantly over-expressed in human HF tissues and located at the cytoplasm of HSCs. Together, dual-luciferase reporter, AGO-RIP and biotin-coupled miRNA capture assays confirmed that circ_0008494 acted as a sponge of miR-185-3p. Cell functional experiments and rescue assays demonstrated suppressing circ_0008494 could inhibit activation, proliferation, migration of HSCs and promote their apoptosis through miR-185-3p. In particular, the HF indicator, Col1a1, was validated as the direct target of miR-185-3p and the suppression of circ_0008494 inhibited the expression of Col1a1 by releasing miR-185-3p. Conclusion: Knocking down circ_0008494 inhibited HSCs activation through the miR-185-3p/Col1a1 axis. circ_0008494 could be a promising treatment target for HF.

A yes-associated protein 1- Notch1 receptor positive feedback loop promotes breast cancer lung metastasis by attenuating the bone morphogenetic protein 4-SMAD family member 1/5 signaling.

The Notch1 (Notch1 receptor) and yes-associated protein 1 (YAP1) signaling can regulate breast cancer metastasis. This study aimed at investigating whether and how these two signal pathways crosstalk to promote breast cancer lung metastasis. Here, we show that YAP1 expression was positively correlated with Notch1 in breast cancer according to bioinformatics and experimental validation. Mechanistically, YAP1 with TEA domain transcription factors (TEADs) enhanced Jagged1(JAG1)-Notch1 signaling. Meanwhile, Notch1 promoted YAP1 stability in breast cancer cells by inhibiting the ß-TrCP-mediated degradation, thereby, forming a YAP1- JAG1/Notch1 positive feedback loop in breast cancer. Furthermore, YAP1 enhanced the mammosphere formation and stemness of MDA-MB-231 cells by attenuating the inhibition of the BMP4-SMAD1/5 signaling. In vivo, the YAP1- JAG1/Notch1 positive feedback loop promoted the lung colonization of MDA-MB-231 cells. Our data for the first time indicate that the YAP1-Notch1 positive feedback loop promotes lung metastasis of breast cancer by modulating self-renewal and inhibiting the BMP4-SMAD1/5 signaling.