Fluoride impairs vascular smooth muscle A7R5 cell lines via disrupting amino acids metabolism.

Given the insidious and high-fatality nature of cardiovascular diseases (CVDs), the emergence of fluoride as a newly identified risk factor demands serious consideration alongside traditional risk factors. While vascular smooth muscle cells (VSMCs) play a pivotal role in the progression of CVDs, the toxicological impact of fluoride on VSMCs remains largely uncharted. In this study, we constructed fluorosis model in SD rats and A7R5 aortic smooth muscle cell lines to confirm fluoride impaired VSMCs. Fluoride aggravated the pathological damage of rat aorta in vivo. Then A7R5 were exposed to fluoride with concentration ranging from 0 to 1200 µmol/L over a 24-h period, revealing a dose-dependent inhibition of cell proliferation and migration. The further metabolomic analysis showed alterations in metabolite profiles induced by fluoride exposure, notably decreasing organic acids and lipid molecules level. Additionally, gene network analysis underscored the frequency of fluoride's interference with amino acids metabolism, potentially impacting the tricarboxylic acid (TCA) cycle. Our results also highlighted the ATP-binding cassette (ABC) transporters pathway as a central element in VSMC impairment. Moreover, we observed a dose-dependent increase in osteopontin (OPN) and α-smooth muscle actin (α-SMA) mRNA level and a dose-dependent decrease in ABC subfamily C member 1 (ABCC1) and bestrophin 1 (BEST1) mRNA level. These findings advance our understanding of fluoride as a CVD risk factor and its influence on VSMCs and metabolic pathways, warranting further investigation into this emerging risk factor.

Distinctive tumorigenic significance and innovative oncology targets of SUMOylation.

Protein SUMOylation, a post-translational modification, intricately regulates diverse biological processes including gene expression, cell cycle progression, signaling pathway transduction, DNA damage response, and RNA metabolism. This modification contributes to the acquisition of tumorigenicity and the maintenance of cancer hallmarks. In malignancies, protein SUMOylation is triggered by various cellular stresses, promoting tumor initiation and progression. This augmentation is orchestrated through its specific regulatory mechanisms and characteristic biological functions. This review focuses on elucidating the fundamental regulatory mechanisms and pathological functions of the SUMO pathway in tumor pathogenesis and malignant evolution, with particular emphasis on the tumorigenic potential of SUMOylation. Furthermore, we underscore the potential therapeutic benefits of targeting the SUMO pathway, paving the way for innovative anti-tumor strategies by perturbing this dynamic and reversible modifying process.

Erratum: A Novel Pak1/ATF2/miR-132 Signaling Axis Is Involved in the Hematogenous Metastasis of Gastric Cancer Cells.

[This corrects the article DOI: 10.1016/j.omtn.2017.07.005.].

Potential roles of PIWI-interacting RNAs in breast cancer, a new therapeutic strategy.

Breast cancer (BC) has been the focus of numerous studies aimed at identifying novel biological markers for its early detection. PIWI-interacting RNAs (piRNAs), a subset of small non-coding RNAs, have emerged as potential markers due to their aberrant expression in various cancers. PiRNAs have recently gained attention due to their aberrant expression in various cancers, including BC. PiRNAs, exhibit diverse biological activities, such as epigenetic regulation of gene and protein expression and their association with cell proliferation and metastasis has been well-established. As the field of non-coding RNAs rapidly evolves, there is great anticipation that therapies targeting piRNAs will advance swiftly. This review will delve into the various biological functions of piRNAs, such as gene suppression, transposon silencing, and epigenetic regulation of genes. The review will also highlight the role of piRNAs as either progenitors or suppressors in cancers, with a particular focus on BC. Lastly, it will touch upon the potential of piRNAs as biomarkers and therapeutic targets for BC.

PAX1 represses canonical Wnt signaling pathway and plays dual roles during endoderm differentiation.

BACKGROUND: Paired box 1 (PAX1) is a transcription factor and essential for the development of pharyngeal pouches-derived tissues, including thymus. PAX1 mutations are identified in Severe Combined Immunodeficiency (SCID) patients with Otofaciocervical Syndrome Type 2 (OTFCS2). However, despite the critical roles of PAX1 in embryonic development and diseases, detailed insights into its molecular mode of action are critically missing. METHODS: The repressing roles of PAX1 and SCID associated mutants on Wnt signaling pathway were investigated by luciferase reporter assays, qRT-PCR and in situ hybridization in HEK293FT, HCT116 cells and zebrafish embryos, respectively. Co-immunoprecipitation (co-IP) and western blotting assays were carried out to identify the molecular mechanisms underlying PAX1's role on Wnt signaling pathway. hESC based endoderm differentiation, flow cytometry, high-throughput sequencing data analysis, and qRT-PCR assays were utilized to determine the roles of PAX1 during endoderm differentiation. RESULTS: Here, we show that PAX1 represses canonical Wnt signaling pathway in vertebrate cells. Mechanically, PAX1 competes with SUMO E3 ligase PIASy to bind to TCF7L2, thus perturbing TCF7L2 SUMOylation level, further reducing its transcriptional activity and protein stability. Moreover, we reveal that PAX1 plays dual roles in hESC-derived definitive and foregut/pharyngeal endoderm cells, which give rise to the thymus epithelium, by inhibiting Wnt signaling. Importantly, our data show PAX1 mutations found in SCID patients significantly compromise the suppressing ability of PAX1 on Wnt signaling. CONCLUSIONS: Our study presents a novel molecular mode of action of PAX1 in regulation of canonical Wnt signaling and endoderm differentiation, thus providing insights for the molecular basis of PAX1 associated SCID, offering better understanding of the behavior of PAX1 in embryogenesis.

Acute Effects of Local High-Frequency Percussive Massage on Deep Fascial and Muscular Stiffness and Joint Range of Motion in Young Adult Men.

BACKGROUND: Local high-frequency percussive (HFP) massage has recently found widespread application in physical therapy. Although HFP massage reportedly improves range of motion (ROM), the mechanism underlying its action has not yet been proven. This study aimed to clarify whether a 5-minute percussive massage regimen affects muscular or connective tissues, such as the deep fascia and deep intermuscular fascia and the change in joint ROM. METHOD: The study sample was calculated using G*Power analysis program, and this study enrolled 15 healthy men who underwent 5-minute HFP massage to the medial gastrocnemius muscle. Shear-wave elastography was used to measure tissue stiffness in the deep fascia, muscle, and deep intermuscular fascia through shear-wave velocity as well as the ROM of the volunteers' ankle joint dorsiflexion before and after the HFP massage. A value of P < .05 was used to declare statistical significance, and post hoc was used to calculate the effect size using G*Power. RESULTS: Shear-wave velocity revealed a significant change in the deep fascia (P = .003; shear-wave velocity: -0.7 m/s) and significant increase in ROM of ankle dorsiflexion (P = .002; increase in ROM: 3.0°) after 5 minutes of HFP massage. However, the muscle and deep intermuscular fascia did not exhibit any significant changes. CONCLUSIONS: HFP massage for 5 minutes modified the stiffness of the deep fascia and concurrently improved the ankle joint-dorsiflexion ROM. This method can be used as an intervention to decrease stiffness of the deep fascia and increase the ROM efficiently.

Sevelamer reverses liver fibrosis by deactivation of hepatic stellate cells.

Liver fibrosis is a chronic liver disease characterized by a progressive wound healing response caused by chronic liver injury. Currently, there are no approved clinical treatments for liver fibrosis. Sevelamer is used clinically to treat hyperphosphatemia and has shown potential therapeutic effects on liver diseases. However, there have been few studies evaluating the therapeutic effects of sevelamer on liver fibrosis, and the specific mechanisms are still unclear. In this study, we investigated the antifibrotic effects of sevelamer-induced low inorganic phosphate (Pi) stress in vitro and in vivo and analyzed the detailed mechanisms. We found that low Pi stress could inhibit the proliferation of activated hepatic stellate cells (HSCs) by promoting apoptosis, effectively suppressing the migration and epithelial-mesenchymal transition (EMT) of hepatic stellate cells. Additionally, low Pi stress significantly increased the antioxidant stress response. It is worth noting that low Pi stress indirectly inhibited the activation and migration of HSCs by suppressing transforming growth factor ß (TGF-ß) expression in macrophages. In a rat model of liver fibrosis, oral administration of sevelamer significantly decreased blood phosphorus levels, improved liver function, reduced liver inflammation, and increased the antioxidant stress response in the liver. Our study revealed that the key mechanism by which sevelamer inhibited liver fibrosis involved binding to gastrointestinal phosphate, resulting in a decrease in blood phosphorus levels, the downregulation of TGF-ß expression in macrophages, and the inhibition of HSC migration and fibrosis-related protein expression. Therefore, our results suggest that sevelamer-induced low Pi stress can attenuate hepatic stellate cell activation and inhibit the progression of liver fibrosis, making it a potential option for the treatment of liver fibrosis and other refractory chronic liver diseases.

Low Body Fat Percentage and Menstrual Cycle Disorders in Female Elite Adolescent Dancers.

Introduction: The menstrual cycle is an important indicator of health in female athletes. Female elite adolescent dancers are expected to control their weight while also training intensely, which can lead to menstrual disorders. This study aimed to investigate the relationship between body composition and menstrual status in female elite adolescent dancers. Methods: In total, 131 female elite adolescent dancers (age: 15.9 ± 1.5 years) were enrolled in this study. We measured the height, weight, and body fat percentage (BFP) for each participant and calculated their body mass index (BMI). We gathered information on individual menstruation patterns and the participants' menstrual cycles over the previous year using recall methods. We then compared the differences between dancers with menstrual cycle disorders and those without. Primary amenorrhea was defined as menarche occurring after the age of 15, while secondary amenorrhe was defined as experiencing fewer than 5 or no menstrual periods for at least 3 of the previous 12 months. We conducted a reliability test using the same questionnaire 2 weeks later. Statistical significance was defined as P < .05, and we calculated the effect sizes (d) and 95% confidence intervals (95% CI). Results: The average BMI and BFP were 22.6 ± 3.0% and 19.4 ± 2.2 kg/m2, respectively. Low BFP and low BMI were observed in 51 (38.6%) and 47 (35.6%) participants, respectively. Primary amenorrhea in 3 participants (2.3%) and 29 (22.1%) reported experiencing secondary amenorrhea; they had lower BFP than the dancers who did not experience amenorrhea (P = .041, 95% CI, -2.51 to -0.05). Conclusion: Female elite adolescent dancers in China may have lower BFP and menstrual problems. Given that lower BFP may contribute to the occurrence of menstruation disorders, it is essential to pay an attention to both BFP and the menstruation status in female elite adolescent dancers.

Synergistic effects of lactobacillus strains and Acetobacter pasteurianus on jujube puree's product functionality and quality.

Commercial lactic acid bacteria strains and indigenous Chinese acetic acid bacterium were co-cultivated bi- and tri-culturally in Junzao jujube puree for the first time to investigate their effects on physicochemical properties and quality attributes. Lactic-acetic acid bacteria co-fermentation was performed at 37 °C for 48 h during the anaerobic fermentation phase and at 30 °C for 144 h during aerobic fermentation. FTIR results showed that predominant wave numbers at 1716-1724 cm-1 and 2922-3307 cm-1 exhibited discernible alterations in the lactic-acetic acid co-fermented jujube purees compared to the control sample. Pearson correlation analysis showed that the flavonoid and flavonol contents were responsible for the enhanced 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) and 2,2-diphenyl-1-picrylhydrazyl scavenging activities of the fermented jujube purees. Consequently, fermented jujube puree from tricultures of Lactobacillus casei, Lactobacillus plantarum, and Acetobacter pasteurianus gave the best results, with the highest phenolics, flavonoid, and flavonol contents and the most improved antioxidative properties and color. Overall, lactic-acetic acid bacteria co-culture holds significant promise in valorizing Junzao jujube purees for functional ingredient development, paving the way for further research into similar interactions with different food matrices or microbial strains.

Lead exposure induces neuronal apoptosis via NFκB p65/RBBP4/Survivin signaling pathway.

Lead (Pb), as a heavy metal that is easily exposed in daily life, can cause damage to various systems of body. Apoptosis is an autonomous cell death process regulated by genes in order to maintain the stability of internal environment, which plays an important role in the development of nervous system. RB binding protein 4 (RBBP4) is one of the core histone binding subunits and is closely related to the apoptosis process of nervous system cells. However, it is not known whether RBBP4 can regulate neuronal apoptosis in lead-exposed environments. We exposed PC12 cells to 0 µM (control group), 1 µM, and 100 µM PbAc for 24 h to obtain cell samples. The female rats ingested drinking water containing 0, 0.5 g/L, and 2.0 g/L PbAc from the first day of pregnancy to three weeks after delivery to obtain hippocampal tissue samples from mammary rats. The results of TUNEL showed that lead exposure promoted the onset of apoptosis in cells and hippocampus. The mRNA and protein levels of the apoptosis-related protein Survivin were significantly reduced in the lead-exposed group compared to the control group. In addition, we found that lead exposure reduces the mRNA and protein levels of RBBP4 in PC12 cells and hippocampus, and increases the mRNA and protein levels of NFκB p65. Moreover, inhibiting NFκB p65 can reverse the decrease in RBBP4 expression in the lead exposure model. Overexpression of RBBP4 increased Survivin expression and reduced apoptosis induced by lead exposure. This suggests that lead exposure induces apoptosis through the NFκB p65/RBBP4/Survivin signaling pathway.

Change in the sub-sesamoid soft tissue thickness under different loading conditions.

[Purpose] To measure the sub-sesamoid soft tissue thickness change from non-loading to self-weight loading conditions. [Participants and Methods] The study included 17 female participants for the study. A questionnaire was used to collect the demographic data and participant anamnesis, such as the presence of foot injuries and diabetes. The measured height and weight were used to calculate the body mass index. Participants were required to stand on an evaluation device from non-loading to 100% loading conditions to measure the sub-sesamoid soft tissue thickness. [Results] Significant differences were observed between the tibial and fibular sub-sesamoid soft tissue thicknesses under non-loading and all loading conditions. Significant soft tissue thinning was observed with a change from non-loading to 25% loading condition. However, no significant differences in the rate of change were observed between the tibial and fibular sub-sesamoid soft tissue thicknesses at 100% loading. [Conclusion] The sub-fibular sesamoid soft tissue was thicker than the sub-tibial sesamoid soft tissue in all loading conditions. The sub-sesamoid soft tissue thickness change was larger during initial loading stage than during the late loading stage, which may be normal in healthy females in their 20s.

Evaluation of the safety and efficacy of transarterial sevelamer embolization in a rabbit liver cancer model: A challenge on the size rule for vascular occlusion.

As the most efficient method to treat hepatocellular carcinoma in the immediate or advanced stage, transarterial chemoembolization (TACE) is coming into the era of microsphere (MP). Drug-eluting beads have shown their huge potential as an embolic agent and drug carrier for chemoembolization, but their sizes are strictly limited to be above 40 µm, which was considered to occlude vessels in a safe mode. microsphere smaller than 40 µm is easy to be washed out and transported to the normal liver lobe or other organs, causing severe adverse events and failed embolization. To determine whether sevelamer ultrafine particle (0.2-0.5 µm) is qualified as a safe and efficient embolic agent, we investigated the safety and therapeutic efficiency of transarterial sevelamer embolization (TASE) in the VX2 rabbit liver cancer model, aiming to challenge the "40 µm" rule on the selection criteria of the MP. In a four-arm study, blank bead (Callisphere, 100-300 µm), luminescent polystyrene microsphere (10, 100 µm), and sevelamer particle were transarterially administered to evaluate the threshold size of the MP size for intrahepatic or extrahepatic permeability. Another four-arm study was designed to clarify the safety and efficiency of preclinical transarterial sevelamer embolizationTASE tests over other techniques. Sham (saline), TASE, C-TACE, and D-TACE (n = 6) were compared in terms of serum chemistry, histopathology, and tumor necrosis ratio. In the first trials, the "40 µm" rule was detectable on the VX2 cancer model, but the regulation has no application to the new embolic agent as sevelamer ultrafine particles have not been found to leak out from the VX2 lesions, only found in the embolized vessels. Pathology proves that less viable tumor residue was found 2 weeks after the procedure, evidencing a better therapeutic outcome. No adverse events were found except for a short stress response. These results indicate that sevelamer is a safe and efficient embolic as an alternative to the current MP-based embolization therapy techniques.

Thermal Error Prediction and Compensation of Digital Twin Laser Cutting Based on T-XGBoost.

Laser cutting belongs to non-contact processing, which is different from traditional turning and milling. In order to improve the machining accuracy of laser cutting, a thermal error prediction and dynamic compensation strategy for laser cutting is proposed. Based on the time-varying characteristics of the digital twin technology, a hybrid model combining the thermal elastic-plastic finite element (TEP-FEM) and T-XGBoost algorithms is established. The temperature field and thermal deformation under 12 common working conditions are simulated and analyzed with TEP-FEM. Real-time machining data obtained from TEP-FEM simulation is used in intelligent algorithms. Based on the XGBoost algorithm and the simulation data set as the training data set, a time-series-based segmentation algorithm (T-XGBoost) is proposed. This algorithm can reduce the maximum deformation at the slit by more than 45%. At the same time, by reducing the average volume strain under most working conditions, the lifting rate can reach 63% at the highest, and the machining result is obviously better than XGBoost. The strategy resolves the uncontrollable thermal deformation during cutting and provides theoretical solutions to the implementation of the intelligent operation strategies such as predictive machining and quality monitoring.

The Effect of Foot Deformity and First Metatarsophalangeal Joint Plantar Pain on Performance in DanceSport Athletes.

BACKGROUND: Adolescent DanceSport athletes who regularly dance in high heels have a higher possibility of developing hallux valgus deformity and foot pain. We believe that the occurrence of foot disorders may change the loading on their feet, which thus affects the athletic performance of those adolescents. METHODS: A total of 63 adolescent DanceSport athletes (16 boys, 47 girls) were included. The plantar pain in the first metatarsophalangeal (1st MTP) joint was evaluated using a questionnaire, and the hallux valgus angle was evaluated using digital photographs (HVAp). The loading values of the plantar pressure while performing relève on demi-pointe were measured using sensor sheets. The participating boys and girls were analyzed separately. RESULTS: The results showed that female adolescent DanceSport athletes with the 1st MTP joint plantar pain showed a decrease in the loading distribution and plantar pressure percentage on the hallux and an increased loading distribution and pressure distribution of the metatarsal head as the HVAp increased. CONCLUSION: Among adolescent DanceSport athletes with plantar pain in the 1st MTP joint and a large HVAp, the loading manner of the foot may have changed, which may be associated with a decrease in the toe function and performance.

Pi-inducedin-situaggregation of sevelamer nanoparticles for vascular embolization.

Decades have witnessed rapid progress of polymeric materials for vascular embolic or chemoembolic applications. Commercially available polymeric embolics range from gelatin foam to synthetic polymers such as poly(vinyl alcohol). Current systems under investigation include tunable, bioresorbable microspheres composed of chitosan or poly(ethylene glycol) derivatives,in situgelling liquid embolics with improved safety profiles, and radiopaque embolics that are trackablein vivo. In this paper, we proposed a concept of 'responsive embolization'. Sevelamer, clinically proved as an inorganic phosphate binder, was ground into nanoparticles. Sevelamer nanoparticle is highly mobile and capable of swelling and aggregating in the presence of endogenous inorganic phosphate, thereby effectively occluding blood flow in the vessel as it was administered as an embolic agent for interventional therapy. Moreover, citrated sevelamer nanoparticles delayed the aggregation, preferable to penetrate deeply into the capillary system. On the rabbit VX2 liver cancer model, both sevelamer particles aggregates occlude the tumor feeding artery, but backflow was found for the pristine one, thereby citrate passivation of sevelamer nanoparticles endows it have potential from 'bench to bedside' as a new type of vascular embolic.

Spotlight on Isl1: A Key Player in Cardiovascular Development and Diseases.

Cardiac transcription factors orchestrate a regulatory network controlling cardiovascular development. Isl1, a LIM-homeodomain transcription factor, acts as a key player in multiple organs during embryonic development. Its crucial roles in cardiovascular development have been elucidated by extensive studies, especially as a marker gene for the second heart field progenitors. Here, we summarize the roles of Isl1 in cardiovascular development and function, and outline its cellular and molecular modes of action, thus providing insights for the molecular basis of cardiovascular diseases.

PAK5 promotes RNA helicase DDX5 sumoylation and miRNA-10b processing in a kinase-dependent manner in breast cancer.

P21-activated kinase 5 (PAK5) plays an important role in tumors. However, the functional role of PAK5 in mammary tumorigenesis in vivo remains unclear. Here, we show that PAK5 deficiency represses MMTV-PyVT-driven breast tumorigenesis. DEAD-box RNA helicase 5 (DDX5) is a substrate of PAK5, which is phosphorylated on threonine 69. PAK5-mediated DDX5 phosphorylation promotes breast cancer cell proliferation and metastasis. The increased expression levels of PAK5 and phospho-DDX5 threonine 69 are associated with metastasis and poor clinical outcomes of patients. PAK5 facilitates the phosphorylation-dependent sumoylation of DDX5 to stabilize DDX5. Both the phosphorylation and sumoylation of DDX5 enhance the formation of a DDX5/Drosha/DGCR8 complex, thus promoting microRNA-10b processing. Finally, we verify decreased expression of DDX5 phosphorylation and sumoylation and mature miR-10b in PAK5-/-/MMTV-PyVT transgenic mice. Our findings provide insights into the function of PAK5 in microRNA (miRNA) biogenesis, which might be a potential therapeutic target for breast cancer.

Comparative evaluation of package types in alleviating textural softening and package-swelling of Paocai during storage: Insight into microbial invasion, cell wall pectinolysis and alteration in sugar and organic acid profiles.

The present study aimed to investigate the effect of initial vacuum package (VP), air package (AP) and salt-solution package (NP) on texture softening and package-swelling of Paocai by comparing the changes in physicochemical properties, pectinolysis, microstructure, microbial profile, as well as sugar and organic acid profiles during storage. Results showed that, when compared with AP and NP, with suppressive microbial invasion and less total pectinase activity, VP could retain more soluble pectin and induce more compact microstructure of Paocai, leading to higher hardness of Paocai during storage. As for package-swelling, VP mitigated gas-production in package by changing the microbial composition and metabolic patterns of sugar and organic acid in Paocai, especially targeted regulating the abundance of genus Kazachstania. This study provided a perspective for appropriate packaging technology to control the pectinase activity as well as cell-invading and gas-producing microorganisms for manufacturing fermented vegetable with better texture and non-package-swelling.

Effect of atrazine on accumulation of iron via the iron transport proteins in the midbrain of SD rats.

Atrazine (ATR), a widely used herbicide that belongs to the triazine class, has detrimental effects on several organ systems. It has also been shown that ATR exposure results in dopaminergic neurotoxicity. However, the mechanism of herbicides causing ferroptosis in neurons is less concerned. So, the present study aimed to investigate the effects of long-term oral exposure to ATR on ferroptosis in adult male rats. In this study, we show that there was a dose-dependent increase in the concentration of iron in the midbrain. Simultaneously, the expression of tyrosine hydroxylase (TH) and Synuclein (α-syn) were altered by the ATR. We carried out miRNA profiling brain tissue in order to identify factors that mediate ferroptosis. We also found that the mRNA and protein expression of the transferrin receptor (TFR), divalent metal transporter 1 (DMT1), hephaestin (HEPH), and ferroportin 1 (Fpn1) in the midbrain were affected by ATR. Based on the current results and previously published data, it is clear that exposure of adult male rats to high doses of ATR leads to iron loading in the midbrain. The long-term adverse effects of ATR on the midbrain have a special relevance after exposure.

PAK5-mediated AIF phosphorylation inhibits its nuclear translocation and promotes breast cancer tumorigenesis.

Although p21 activated kinase 5 (PAK5) is related to the progression of multiple cancers, its biological function in breast cancer remains unclear. Apoptosis-inducing factor (AIF) is a vital apoptosis factor in mitochondria, which can be released from mitochondria and enter the nucleus, causing caspase-independent apoptosis. In this study, we reveal that PAK5 inhibits apoptosis by preventing the nuclear translocation of AIF. PAK5 inhibits the release of AIF from mitochondria in breast cancer cells by decreasing the mitochondria membrane permeability and increasing the membrane potential. Furthermore, PAK5 phosphorylates AIF at Thr281 site to inhibit the formation of AIF/importin α3 complex, leading to decrease AIF nuclear translocation. Functionally, we demonstrate that PAK5-mediated AIF phosphorylation promotes the proliferation of breast cancer cells and accelerates the growth of breast cancer in vivo. Significantly, PAK5 and AIF expression in breast cancer are positively correlated with poor patient prognosis. PAK5 expression is negatively correlated with AIF nuclear translocation. These results suggest that PAK5-AIF signaling pathway may play an essential role in mammary tumorigenesis, providing a new therapeutic target for the treatment of breast cancer.