Nynrin preserves hematopoietic stem cell function by inhibiting the mitochondrial permeability transition pore opening.

Mitochondria are key regulators of hematopoietic stem cell (HSC) homeostasis. Our research identifies the transcription factor Nynrin as a crucial regulator of HSC maintenance by modulating mitochondrial function. Nynrin is highly expressed in HSCs under both steady-state and stress conditions. The knockout Nynrin diminishes HSC frequency, dormancy, and self-renewal, with increased mitochondrial dysfunction indicated by abnormal mPTP opening, mitochondrial swelling, and elevated ROS levels. These changes reduce HSC radiation tolerance and promote necrosis-like phenotypes. By contrast, Nynrin overexpression in HSCs diminishes irradiation (IR)-induced lethality. The deletion of Nynrin activates Ppif, leading to overexpression of cyclophilin D (CypD) and further mitochondrial dysfunction. Strategies such as Ppif haploinsufficiency or pharmacological inhibition of CypD significantly mitigate these effects, restoring HSC function in Nynrin-deficient mice. This study identifies Nynrin as a critical regulator of mitochondrial function in HSCs, highlighting potential therapeutic targets for preserving stem cell viability during cancer treatment.

Reform of teaching and practice of the integrated teaching method BOPPPS-PBL in the course "clinical haematological test technique".

BACKGROUND: In order to meet the demand for laboratory talents in the clinical laboratory industry and address the current curriculum characteristics and shortcomings of the teaching mode of "Clinical Hematology Laboratory Technology", we investigated the effectiveness of the bridge-in, objective, pre-assessment, participatory learning, post-assessment, and summary model combined with problem-based learning (BOPPPS-PBL) in undergraduate teaching of this course. METHOD: Seventy students majoring in Medical Laboratory Technology from the Army Medical University in the past 5 years have been selected and divided into two groups with the same teaching content and time. The control group (2015 and 2016 grades) used traditional teaching methods, while the experimental group (2017, 2018 and 2019 grades) used the BOPPPS-PBL model. After class, diverse evaluation methods were used to analyze the formative and summative exam scores of the two groups of students. RESULTS: After the reform, students performed significantly better in exams than before. In addition, the new teaching methods have had a positive impact, with students demonstrating high motivation for self-directed learning and problem-solving abilities. CONCLUSION: Compared to traditional teaching methods. The BOPPPS-PBL integrated case study education model is a relatively effective teaching method to improve students' problem-solving ability and comprehensive practical ability.

The ω-3 Polyunsaturated Fatty Acid Docosahexaenoic Acid Enhances NK-Cell Antitumor Effector Functions.

ω-3 polyunsaturated fatty acids (PUFA) are known to directly repress tumor development and progression. In this study, we explored whether docosahexaenoic acid (DHA), a type of ω-3 PUFA, had an immunomodulatory role in inhibiting tumor growth in immunocompetent mice. The number of natural killer (NK) cells but not the number of T or B cells was decreased by DHA supplementation in various tissues under physiologic conditions. Although the frequency and number of NK cells were comparable, IFNγ production by NK cells in both the spleen and lung was increased in DHA-supplemented mice in the mouse B16F10 melanoma tumor model. Single-cell RNA sequencing revealed that DHA promoted effector function and oxidative phosphorylation in NK cells but had no obvious effects on other immune cells. Using Rag2-/- mice and NK-cell depletion by PK136 antibody injection, we demonstrated that the suppression of B16F10 melanoma tumor growth in the lung by DHA supplementation was dependent mainly on NK cells. In vitro experiments showed that DHA directly enhanced IFNγ production, CD107a expression, and mitochondrial oxidative phosphorylation (OXPHOS) activity and slightly increased proliferator-activated receptor gamma coactivator-1α (PGC-1α) protein expression in NK cells. The PGC-1α inhibitor SR-18292 in vitro and NK cell-specific knockout of PGC-1α in mice reversed the antitumor effects of DHA. In summary, our findings broaden the current knowledge on how DHA supplementation protects against cancer growth from the perspective of immunomodulation by upregulating PGC-1α signaling-mediated mitochondrial OXPHOS activity in NK cells.

Critical Influence of Organic A'-Site Ligand Structure on 2D Perovskite Crystallization.

Organic A'-site ligand structure plays a crucial role in the crystal growth of 2D perovskites, but the underlying mechanism has not been adequately understood. This problem is tackled by studying the influence of two isomeric A'-site ligands, linear-shaped n-butylammonium (n-BA+ ) and branched iso-butylammonium (iso-BA+ ), on 2D perovskites from precursor to device, with a combination of in situ grazing-incidence wide-angle X-ray scattering and density functional theory. It is found that branched iso-BA+ , due to the lower aggregation enthalpies, tends to form large-size clusters in the precursor solution, which can act as pre-nucleation sites to expedite the crystallization of vertically oriented 2D perovskites. Furthermore, iso-BA+ is less likely to be incorporated into the MAPbI3 lattice than n-BA+ , suppressing the formation of unwanted multi-oriented perovskites. These findings well explain the better device performance of 2D perovskite solar cells based on iso-BA+ and elucidate the fundamental mechanism of ligand structural impact on 2D perovskite crystallization.

Promoting the Efficiency and Stability of Nonfullerene Organic Photovoltaics by Incorporating Open-Cage [60]Fullerenes in the Nonfullerene Nanocrystallites.

The device efficiency of PM6:Y6-based nonfullerene organic solar cells is fast advanced recently. To maintain organic solar cells (OSCs) with high power conversion efficiency over 16% in long-term operation, however, remains a challenge. Here, a novel non-volatile additive, an open-cage [60]fullerene (8OC60Me), is incorporated into PM6:Y6-based OSCs for high-performance with high durability. With optimized addition of 1.0 wt % 8OC60Me, the PCE value of PM6:Y6/8OC60Me OSCs can be promoted to 16.5% from 15.0%. Most strikingly, such a high PCE performance can maintain nearly 100% for over 500 h at room temperature; at an elevated operation temperature of 80 °C, the PCE can be stabilized above 15.0% after 45 h of operation. Grazing incidence small- and wide- angle X-ray scattering studies reveal improved orientation and crystallinity of Y6 in a fractal-like network structure of PM6 in PM6:Y6/8OC60Me films under in situ annealing, parallel to the enhanced electron mobility. Analysis of charge distributions lines up possible van der Waals interaction between the thienyl/carbonyl moiety of 8OC60Me and difluorophenyl-based FIC-end groups of Y6. This result is of great contrast to those devices with the best-selling PC61BM as the additives─8OC60Me might be of interest to be incorporated into future Y6-based OSCs for concomitantly improved PCE and excellent stability.

Insufficiency of FZR1 disturbs HSC quiescence by inhibiting ubiquitin-dependent degradation of RUNX1 in aplastic anemia.

FZR1 has been implicated as a master regulator of the cell cycle and quiescence, but its roles and molecular mechanisms in the pathogenesis of severe aplastic anemia (SAA) are unclear. Here, we report that FZR1 is downregulated in SAA HSCs compared with healthy control and is associated with decreased quiescence of HSC. Haploinsufficiency of Fzr1 shows impaired quiescence and self-renewal ability of HSC in two Fzr1 heterozygous knockout mouse models. Mechanistically, FZR1 insufficiency inhibits the ubiquitination of RUNX1 protein at lysine 125, leading to the accumulation of RUNX1 protein, which disturbs the quiescence of HSCs in SAA patients. Moreover, downregulation of Runx1 reversed the loss of quiescence and impaired long-term self-renew ability in Fzr1+/- HSCs in vivo and impaired repopulation capacity in BM from SAA patients in vitro. Our findings, therefore, raise the possibility of a decisive role of the FZR1-RUNX1 pathway in the pathogenesis of SAA via deregulation of HSC quiescence.

Nuclear DEK preserves hematopoietic stem cells potential via NCoR1/HDAC3-Akt1/2-mTOR axis.

The oncogene DEK is found fused with the NUP214 gene creating oncoprotein DEK-NUP214 that induces acute myeloid leukemia (AML) in patients, and secreted DEK protein functions as a hematopoietic cytokine to regulate hematopoiesis; however, the intrinsic role of nuclear DEK in hematopoietic stem cells (HSCs) remains largely unknown. Here, we show that HSCs lacking DEK display defects in long-term self-renew capacity, eventually resulting in impaired hematopoiesis. DEK deficiency reduces quiescence and accelerates mitochondrial metabolism in HSCs, in part, dependent upon activating mTOR signaling. At the molecular level, DEK recruits the corepressor NCoR1 to repress acetylation of histone 3 at lysine 27 (H3K27ac) and restricts the chromatin accessibility of HSCs, governing the expression of quiescence-associated genes (e.g., Akt1/2, Ccnb2, and p21). Inhibition of mTOR activity largely restores the maintenance and potential of Dek-cKO HSCs. These findings highlight the crucial role of nuclear DEK in preserving HSC potential, uncovering a new link between chromatin remodelers and HSC homeostasis, and have clinical implications.

Zfp521 is essential for the quiescence and maintenance of adult hematopoietic stem cells under stress.

Zinc finger protein 521 (Zfp521), a quiescent hematopoietic stem cell (HSC)-enriched transcription factor, is involved in the self-renewal and differentiation of fetal liver HSC. However, its role in adult hematopoiesis remains elusive. Here, we found that Zfp521 deletion did not inhibit adult hematopoiesis under homeostatic conditions. In contrast, Zfp521-null chimeric mice showed significantly reduced pool size of HSC and hematopoietic progenitor cells associated with increased apoptosis and loss of quiescence. Competitive serial transplantation assays revealed that Zfp521 regulates HSC self-renewal and differentiation under regenerative stress. Mechanistically, Zfp521 transcriptionally repressed Rela expression by increasing H3K9ac and decreasing H3K9me3 levels in its promoter. Knockdown of Rela inhibited the hyper-activated NF-κB pathway and reversed the loss of quiescence in Zfp521-null HSC under stress. Thus, our results reveal a previously unrecognized role for Zfp521 as critical regulator of quiescence and self-renewal of HSC in adult hematopoiesis mediated at least partly by controlling Rela expression.

Exercise protects proliferative muscle satellite cells against exhaustion via the Igfbp7-Akt-mTOR axis.

Background and Purpose: The exhaustion of muscle satellite cells (SCs) is correlated with muscle diseases, including sarcopenia and Duchenne muscular dystrophy. Exercise benefits skeletal muscle homeostasis and promotes proliferation of SCs. Elucidating the molecular mechanism underlying the muscle function-improving effect of exercise has important implications in regenerative medicine. Methods: Herein, we investigated the effect of 4-week treadmill training on skeletal muscle and SCs in mice. Hematoxylin and eosin (HE) staining was utilized to detect the morphometry of skeletal muscles. Flow cytometry and immunofluorescence were conducted to analyze the abundance and cell cycle of SCs. RNA sequencing was performed to elucidate the transcriptional regulatory network of SCs. The ChIP-PCR assay was used to detect enrichment of H3K27ac at the promoters of Akt. Results: We observed that exercise resulted in muscle hypertrophy and improved muscle regeneration in mice. Unexpectedly, exercise promoted cell cycling but suppressed the Akt-mTOR pathway in SCs. Proliferative SCs in "exercised mice" required suppressed mTOR activity to limit mitochondrial metabolism, maintaining the "limited activation status" of SCs against exhaustion. Mechanistically, exercise upregulated the expression of Igfbp7, thereby impeding the phosphorylation of Akt and resulting in inhibited mTOR activity and limited mitochondrial metabolism. The limited mitochondrial metabolism resulted in hypoacetylation of histone 3 and reduced enrichment of H3K27ac at promoters of Akt, decreasing the transcription of Akt. Moreover, repeatedly injured mice showed a preserved SC pool and improved muscle regeneration by the suppression of Akt-mTOR signaling. Conclusions: The findings of our study show that exercise protects proliferative SCs against exhaustion via the Igfbp7-Akt-mTOR axis. These findings establish a link between mechanical signaling, mitochondrial metabolism, epigenetic modification, and stem cell fate decisions; thus, present potential therapeutic targets for muscle diseases correlated with SC exhaustion.

Oligomerization of IC43 resulted in improved immunogenicity and protective efficacy against Pseudomonas aeruginosa lung infection.

IC43, a truncate form of outer membrane proteins OprF190-342 and OprI21-83 from Pseudomonas aeruginosa, is a promising candidate antigen and exists as monomer in solution. In this study, we generated the heptamer of IC43 by carrier protein aided oligomerization, which was confirmed by gel-filtration and chemical cross-linking analysis. The carrier protein naturally exists as a homo-heptamer, and IC43 was displayed on the surface of the carrier protein in the fusion protein. Immunization with this fusion protein resulted in increased level of antigen specific IgG antibodies and higher survival rate after infection. The improved efficacy was correlated with lower bacteria burden, inflammation and tissue damage in the lungs of immunized mice. Further studies revealed that immunization with this fusion protein resulted in increased levels of IL-4 and antigen specific IgG1, suggesting a stronger Th2 immune response was induced. The improved immunogenicity may be attributed to the exposure of more epitopes on the antigen, which was confirmed by results from immune-dominant peptide mapping and passive immunization. These results demonstrated a possible strategy to improve the immunogenicity of an antigen by carrier protein aided oligomerization.

A Cdh1-FoxM1-Apc axis controls muscle development and regeneration.

Forkhead box M1 (FoxM1) transcriptional factor has a principal role in regulating cell proliferation, self-renewal, and tumorigenesis. However, whether FoxM1 regulates endogenous muscle development and regeneration remains unclear. Here we found that loss of FoxM1 in muscle satellite cells (SCs) resulted in muscle atrophy and defective muscle regeneration. FoxM1 functioned as a direct transcription activator of adenomatous polyposis coli (Apc), preventing hyperactivation of wnt/ß-catenin signaling during muscle regeneration. FoxM1 overexpression in SCs promoted myogenesis but impaired muscle regeneration as a result of spontaneous activation and exhaustion of SCs by transcriptional regulation of Cyclin B1 (Ccnb1). The E3 ubiquitin ligase Cdh1 (also termed Fzr1) was required for FoxM1 ubiquitylation and subsequent degradation. Loss of Cdh1 promoted quiescent SCs to enter into the cell cycle and the SC pool was depleted by serial muscle injuries. Haploinsufficiency of FoxM1 ameliorated muscle regeneration of Cdh1 knock-out mice. These data demonstrate that the Cdh1-FoxM1-Apc axis functions as a key regulator of muscle development and regeneration.

Directed Vertical Diffusion of Photovoltaic Active Layer Components into Porous ZnO-Based Cathode Buffer Layers.

Cathode buffer layers (CBLs) can effectively further the efficiency of polymer solar cells (PSCs), after optimization of the active layer. Hidden between the active layer and cathode of the inverted PSC device configuration is the critical yet often unattended vertical diffusion of the active layer components across CBL. Here, a novel methodology of contrast variation with neutron and anomalous X-ray reflectivity to map the multicomponent depth compositions of inverted PSCs, covering from the active layer surface down to the bottom of the ZnO-based CBL, is developed. Uniquely revealed for a high-performance model PSC are the often overlooked porosity distributions of the ZnO-based CBL and the differential diffusions of the polymer PTB7-Th and fullerene derivative PC71 BM of the active layer into the CBL. Interface modification of the ZnO-based CBL with fullerene derivative PCBEOH for size-selective nanochannels can selectively improve the diffusion of PC71 BM more than that of the polymer. The deeper penetration of PC71 BM establishes a gradient distribution of fullerene derivatives over the ZnO/PCBE-OH CBL, resulting in markedly improved electron mobility and device efficiency of the inverted PSC. The result suggests a new CBL design concept of progressive matching of the conduction bands.

Immunization with Pseudomonas aeruginosa outer membrane vesicles stimulates protective immunity in mice.

Pseudomonas aeruginosa is an opportunistic pathogen responsible for a wide range of severe nosocomial and community acquired infections, these infections are major health problems for cystic fibrosis patients and immune-compromised individuals. The emergence of multidrug-resistant isolates highlights the need to develop alternative strategies for treatment of P. aeruginosa infections. Outer membrane vesicles (OMVs) are spherical nanometer-sized proteolipids that are secreted from numerous of pathogenic Gram-negative bacteria, and a number of studies have confirmed the protective efficacy for use of OMVs as candidate vaccines. In this study, OMVs from P. aeruginosa (PA_OMVs) were isolated, formulated with aluminum phosphate adjuvant and used as a vaccine in a mouse model of acute lung infection. The results confirmed that active immunization with PA_OMVs was able to reduce bacterial colonization, cytokine secretion and tissue damage in the lung tissue, thus protecting mice from lethal challenge of P. aeruginosa. Cytokines assay validated that immunization with PA_OMVs was efficient to induce a mixed cellular immune response in mice. Further, high level of specific antibodies was detected in mice immunized with PA_OMVs, and results from opsonophagocytic killing assay and passive immunization suggested that humoral immune response may be critical for PA_OMVs mediated protection. These findings demonstrated that PA_OMVs may be served as a novel candidate vaccine for the prevention of P. aeruginosa infection.

CCN1/Cyr61 enhances the function of hepatic stellate cells in promoting the progression of hepatocellular carcinoma.

Hepatic stellate cells (HSCs) are the main extracellular matrix (ECM)­producing cells in liver fibrosis. Activated HSCs stimulate the proliferation and migration of hepatocellular carcinoma (HCC) cells. Cysteine­rich 61 (CCN1/Cyr61) is an ECM protein. Our previous studies demonstrated that the expression of CCN1 was significantly higher in benign hepatic cirrhosis tissue and cancer­adjacent hepatic cirrhosis tissues. CCN1 is a target gene of ß­catenin in HCC and promotes the proliferation of HCC cells. The present study aimed to examine whether CCN1 can activate HSCs and affect the function of activated HSCs in promoting the progression of HCC. CCN1 expression was determined during the progression of liver fibrosis in a mouse model. LX­2 cells, which were infected with adenoviruses AdCCN1 or AdRFP, and HepG2 cells were co­cultured or subcutaneously co­implanted into in nude mice. MTT assay, Crystal Violet staining, Boyden chamber, matrigel invasion and monolayer scratch assays were used to analyze the proliferation, migration and invasion capability of HepG2 cells. Xenograft sizes were measured and histological analyses were performed by hematoxylin and eosin, immunohistochemical, immunefluorescence and Sirius Red staining. It was demonstrated that the expression of CCN1 was continually increased in liver fibrosis and the that expression may be correlated with the progression of liver fibrosis. CCN1 affected the function of LX­2 and enhanced the effect of LX­2 on promoting the viability, migration and invasion of HepG2 cells in vitro. CCN1 enhanced the effect of LX­2 on promoting the growth of HepG2 xenografts in vivo. CCN1 also affected the function of activated HSCs and regulated the formation of the xenograft microenvironment, including fibrogenesis and angiogenesis, which are beneficial for the progression of HCC. These findings demonstrated that CCN1 may be involved in the progression of the hepatic cirrhosis­HCC axis through regulating HSCs.

Probing the Acid-Induced Packing Structure Changes of the Molten Globule Domains of a Protein near Equilibrium Unfolding.

Using simultaneously scanning small-angle X-ray scattering (SAXS) and UV-vis absorption with integrated online size exclusion chromatography, supplemental with molecular dynamics simulations, we unveil the long-postulated global structure evolution of a model multidomain protein bovine serum albumin (BSA) during acid-induced unfolding. Our results differentiate three global packing structures of the three molten globule domains of BSA, forming three intermediates I1, I2, and E along the unfolding pathway. The I1-I2 transition, overlooked in all previous studies, involves mainly coordinated reorientations across interconnected molten globule subdomains, and the transition activates a critical pivot domain opening of the protein for entering into the E form, with an unexpectedly large unfolding free energy change of -9.5 kcal mol-1, extracted based on the observed packing structural changes. The revealed local packing flexibility and rigidity of the molten globule domains in the E form elucidate how collective motions of the molten globule domains profoundly influence the folding-unfolding pathway of a multidomain protein.

A small angle X-ray scattering study of the structure and development of looseness in bovine hides and leather.

BACKGROUND: Some bovine hides produce poor quality leather, termed loose leather. The structural characteristics of hides and the intermediate processed stages that lead to loose leather are not well understood. In the present study, synchrotron-based small angle X-ray scattering (SAXS) is used to investigate collagen fibril orientation at the different stages of processing (i.e. from hide through to leather) that result in both tight and loose leathers. RESULTS: Tight leather of a relatively isotropic texture has a lower orientation index (OI) than loose leather of a more pronounced stratified texture; conversely, tight pickled hide and wet blue have a higher OI than loose pickled hide and wet blue. There is a greater increase in OI on processing from pickled hide to dry crust (leather) for loose material. This is largely the result of a greater increase in hide thickness prior to pickling for loose hide than tight hide, followed by a greater decrease at the dry crust stage. The collagen fibrils in loose leather and wet blue more readily orient under stress than do those in tight leather. Loose leather has a more pronounced layered structure than tight leather, although this difference is not apparent from SAXS measurements of hide prior to the dry crust stage; it develops during processing. CONCLUSION: The greater swelling of the loose hide during processing disrupts the structure and leads to a more layered collagen arrangement on shrinking at the final dry crust stage. © 2016 Society of Chemical Industry.

Immunization with Heat Shock Protein A and γ-Glutamyl Transpeptidase Induces Reduction on the Helicobacter pylori Colonization in Mice.

The human gastric pathogen Helicobacter pylori (H. pylori) is a successful colonizer of the stomach. H. pylori infection strongly correlates with the development and progression of chronic gastritis, peptic ulcer disease, and gastric malignances. Vaccination is a promising strategy for preventing H. pylori infection. In this study, we evaluated the candidate antigens heat shock protein A (HspA) and H. pylori γ-glutamyl transpeptidase (GGT) for their effectiveness in development of subunit vaccines against H. pylori infection. rHspA, rGGT, and rHspA-GGT, a fusion protein based on HspA and GGT, were constructed and separately expressed in Escherichia coli and purified. Mice were then immunized intranasally with these proteins, with or without adjuvant. Immunized mice exhibited reduced bacterial colonization in stomach. The highest reduction in bacterial colonization was seen in mice immunized with the fusion protein rHspA-GGT when paired with the mucosal adjuvant LTB. Protection against H. pylori colonization was mediated by a strong systemic and localized humoral immune response, as well as a balanced Th1/Th2 cytokine response. In addition, immunofluorescence microscopy confirmed that rHspA-GGT specific rabbit antibodies were able to directly bind H. pylori in vitro. These results suggest antibodies are essential to the protective immunity associated with rHspA-GGT immunization. In summary, our results suggest HspA and GGT are promising vaccine candidates for protection against H. pylori infection.

Correlated changes in structure and viscosity during gelatinization and gelation of tapioca starch granules.

Melting of native tapioca starch granules in aqueous pastes upon heating is observed in situ using simultaneous small- and wide-angle X-ray scattering (SAXS/WAXS) and solution viscometry. Correlated structure and viscosity changes suggest closely associated amylose and amylopectin chains in the semicrystalline layers, and the release of amylose chains for enhanced solution viscosity occurs largely after melting of the semicrystalline structure. Before melting, WAXS results reveal mixed crystals of A- and B-types (∼4:1 by weight), whereas SAXS results indicate that the semicrystalline layers are composed of lamellar blocklets of ca 43 nm domain size, with polydisperse crystalline (≃7.5 nm) and amorphous (≃1.1 nm) layers alternatively assembled into a lamellar spacing of ≃8.6 nm with 20% polydispersity. Upon melting, the semicrystalline lamellae disintegrate into disperse and molten amylopectin nanoclusters with dissolved and partially untangled amylose chains in the aqueous matrix which leads to increased solution viscosity. During subsequent cooling, gelation starts at around 347 K; successively increased solution viscosity coincides with the development of nanocluster aggregation to a fractal dimension ≃2.3 at 303 K, signifying increasing intercluster association through collapsed amylose chains owing to decreased solvency of the aqueous medium with decreasing temperature.

Wnt5a enhances the response of CML cells to Imatinib Mesylate through JNK activation and γ-catenin inhibition.

Imatinib Mesylate is widely used for the treatment of chronic myelogenous leukaemia (CML), and its effects on CML cells are influenced by several signalling proteins. The research is aimed at determining whether Wnt5a affects the effects of Imatinib Mesylate against BCR-ABL positive CML cells (K562 cells and KU812 cells) and which signalling proteins are involved in. The results showed that Wnt5a augmented the effects of Imatinib Mesylate on inhibiting CML cells proliferation and inducing apoptosis in vitro; Wnt5a enhanced the inhibition effect of Imatinib Mesylate on the growth of K562 cells xenograft tumour in an animal model. Furthermore, Wnt5a inhibited ß-catenin and its target gene Survivin, increased the activity of JNK and suppressed γ-catenin expression. When inhibiting the activity of JNK, the influence of Wnt5a on the effects of Imatinib Mesylate was attenuated. Moreover, JNK suppressed ß-catenin and its target gene Survivin, and enhanced the effects of Imatinib Mesylate. These results suggest that Wnt5a can enhance the efficacy of Imatinib Mesylate through JNK/ß-catenin/Survivin and γ-catenin/ß-catenin/Survivin pathways.