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Zero-Shot Learning (ZSL) involves transferring knowledge from seen classes to unseen classes by establishing connections between visual and semantic spaces. Traditional ZSL methods identify novel classes by class-level attribute vectors, which implies an information bottleneck. These approaches often use class-level attribute vectors as the fitting target during training, disregarding the individual variations within a class. Moreover, the attributes used for training lack location information and are prone to mismatch with local regions of visual features. To this end, we introduce a Near-Instance-Level Attribute Bottleneck (IAB) to alter class-level attribute vectors as well as visual features throughout the training phase to better reflect their naturalistic correspondences. Specifically, our Near-Instance-Wise Attribute Adaptation (NAA) modifies class attribute vectors to obtain multiple attribute basis vectors, generating a subspace that is more relevant to instance-level samples. Additionally, our Vision Attribute Relation Strengthening (VARS) module searches for attribute-related regions within the features, offering additional location information during the training phase. The proposed method is evaluated on four ZSL benchmarks, revealing that it is superior or competitive to the state-of-the-art methods on ZSL and the more challenging Generalized Zero-Shot Learning (GZSL) settings. Extensive experiments corroborate the sustainability of this study as one of the most potential directions for ZSL, i.e., the effectiveness of enhancing the visual-semantic relationships formed during training using a simple model structure. Code is available at: https://github.com/LanchJL/IAB-GZSL. [ABSTRACT FROM AUTHOR]

Objectives. Erectile dysfunction is a major comorbidity of diabetes. Stem cell transplantation is a promising method to treat diabetic erectile dysfunction. In this study, we evaluated whether low-intensity pulsed ultrasound (LIPUS) could enhance the efficacy of adipose-derived stem cells (ADSCs) and investigated the underlying molecular mechanism. Materials and methods. Sixty 8-week-old male Sprague–Dawley rats were randomly divided into the normal control (NC) cohort or the streptozocin-induced diabetic ED cohort, which was further subdivided into DM, ADSC, LIPUS, and ADSC+LIPUS groups. Rats in the ADSC or ADSC+LIPUS group received ADSC intracavernosal injection. Rats in the LIPUS or ADSC+LIPUS group were treated with LIPUS. The intracavernous pressure (ICP) and mean arterial pressure (MAP) were recorded at Day 28 after injection. The corpus cavernosum tissues were harvested and subjected to histologic analysis and ELISA. The effects of LIPUS on proliferation and cytokine secretion capacity of ADSCs were assessed in vitro. RNA sequencing and bioinformatic analysis were applied to predict the mechanism involved, and western blotting and ELISA were used for verification. Results. Rats in the ADSC+LIPUS group achieved significantly higher ICP and ICP/MAP ratios than those in the DM, ADSC, and LIPUS groups. In addition, the amount of cavernous endothelium and cGMP level also increased significantly in the ADSC+LIPUS group. In vitro experiments demonstrated that LIPUS promoted proliferation and cell cycle progression in ADSCs. The excretion of cytokines such as CXCL12, FGF2, and VEGF was also enhanced by LIPUS. Bioinformatic analysis based on RNA sequencing indicated that LIPUS stimulation might activate the MAPK pathway. We confirmed that LIPUS enhanced ADSC VEGF secretion through the Piezo-ERK pathway. Conclusion. LIPUS enhanced the curative effects of ADSCs on diabetic erectile dysfunction through the activation of the Piezo-ERK-VEGF pathway. ADSC transplantation combined with LIPUS could be applied as a synergistic treatment for diabetic ED. [ABSTRACT FROM AUTHOR]

Compositional Zero-Shot Learning (CZSL) is a particular Zero-Shot Learning (ZSL) task that aims to utilize known concepts (e.g. , states and objects) to identify novel state-object compositions for Image Classification. Previous works have primarily focused on disentangling concept compositions or exploring the complex interactions between the states and objects while neglecting the critical fact that the inference of many states and compositions is related to different frequency components, which should be analyzed from the global perspective. Therefore, we propose a Spatial-frequency Feature Fusion Network (SFFNet) to introduce a new branch that utilizes a frequency-domain filtering encoder to enhance key frequency components and capture non-local interactions adaptively. Besides, we also find that the widely used backbone in conventional CZSL settings behaves superior in perceiving local features. Thus, we construct a fusion block to combine both strengths to capture the local and non-local information. In addition, the traditional one-hot ground-truth distribution in the training phase does not reflect the accurate relationships between compositions, so we propose a composition-relation based label distribution regularization to encourage the model to actively learn the inner relationships between compositions, and extend this method to construct unseen composition pseudo distribution to further enhance the model's generalization ability to unseen compositions. Extensive experiments and detailed analysis are conducted on three popular datasets, and the results show that our method can achieve state-of-the-art performance, which reveals its superiority in identifying novel compositions. Code is available at https://github.com/lisuyi/SFFNet_czsl. • A fusion method for spatial and frequency features is devised for the CZSL task. • Hierarchy information is used in calibrating distribution for both seen and unseen compositions. • The proposed method achieves State-of-The-Art performance on three widely used datasets. [ABSTRACT FROM AUTHOR]

Compositional Zero-Shot Learning (CZSL) aims to recognize unseen compositions from seen states and objects. The disparity between the manually labeled semantic information and its actual visual features causes a significant imbalance of visual deviation in the distribution of various object classes and state classes, which is ignored by existing methods. To ameliorate these issues, we consider the CZSL task as an unbalanced multi-label classification task and propose a novel method called MU tual balancing in ST ate-object components (MUST) for CZSL, which provides a balancing inductive bias for the model. In particular, we split the classification of the composition classes into two consecutive processes to analyze the entanglement of the two components to get additional knowledge in advance, which reflects the degree of visual deviation between the two components. We use the knowledge gained to modify the model's training process in order to generate more distinct class borders for classes with significant visual deviations. Extensive experiments demonstrate that our approach significantly outperforms the state-of-the-art on MIT-States, UT-Zappos, and C-GQA when combined with the basic CZSL frameworks, and it can improve various CZSL frameworks. Our code is available at https://github.com/LanchJL/MUST. • The method considers CZSL as an unbalanced multi-label classification, utilizing visual deviation of components to provide an inductive bias. • Component imbalance info is used to re-weight CZSL training, enabling the model to reconstruct inter-component balance. • The method outperforms SoTAs with base CZSL methods, and augments joint embedding function based approaches. [ABSTRACT FROM AUTHOR]

Metal–organic frameworks (MOFs) have been broadly applied in biomedical and other fields. MOFs have high porosity, a large comparative area, and good biostability and have attracted significant attention, especially in cancer therapies. This paper presents the latest applications of MOFs in chemodynamic therapy (CDT), sonodynamic therapy (SDT), photodynamic therapy (PDT), photothermal therapy (PTT), immunotherapy (IT), and combination therapy for breast cancer. A combination therapy is the combination of two different treatment modalities, such as CDT and PDT combination therapy, and is considered more effective than separate therapies. Herein, we have also discussed the advantages and disadvantages of combination therapy in the treatment of breast cancer. This paper aims to illustrate the potential of MOFs in new cancer therapeutic approaches, discuss their potential advantages, and provide some reflections on the latest research results. [ABSTRACT FROM AUTHOR]

Metal–organic frameworks (MOFs) combined with sonodynamic therapy (SDT) have been introduced as a new and efficient treatment method. The critical advantage of SDT is its ability to penetrate deep tissues and concentrate energy on the tumor site to achieve a non-invasive or minimally invasive effect. Using a sonosensitizer to generate reactive oxygen species (ROS) under ultrasound is the primary SDT-related method of killing tumor cells. In the presence of a sonosensitizer, SDT exhibits a more lethal effect on tumors. The fast development of micro/nanotechnology has effectively improved the efficiency of SDT, and MOFs have been broadly evaluated in SDT due to their easy synthesis, easy surface functionalization, high porosity, and high biocompatibility. This article reviews the main mechanism of action of sonodynamic therapy in cancer treatment, and also reviews the applications of MOFs in recent years. The application of MOFs in sonodynamic therapy can effectively improve the targeting ability of SDT and the conversion ability of reactive oxygen species, thus improving their killing ability on cancer cells. This provides new ideas for the application of micro/nano particles in SDT and cancer therapy. [ABSTRACT FROM AUTHOR]

Myofibroblast buildup and prostatic fibrosis play a crucial role in the development of benign prostatic hyperplasia (BPH). Treatments specifically targeting myofibroblasts could be a promising approach for treating BPH. Tadalafil, a phosphodiesterase type 5 (PDE5) inhibitor, holds the potential to intervene in this biological process. This study employs prostatic stromal fibroblasts to induce myofibroblast differentiation through TGFβ1 stimulation. As a result, tadalafil significantly inhibited prostatic stromal fibroblast proliferation and fibrosis process, compared to the control group. Furthermore, our transcriptome sequencing results revealed that tadalafil inhibited FGF9 secretion and simultaneously improved miR-3126-3p expression via TGFβ1 suppression. Overall, TGFβ1 can trigger pro-fibrotic signaling through miR-3126-3p in the prostatic stroma, and the use of tadalafil can inhibit this process. [ABSTRACT FROM AUTHOR]

Tumors are one of the biggest threats to human life and health. Treatment methods for tumors include chemotherapy, radiotherapy, immunotherapy, etc. These treatment methods have promising therapeutic effects but at the same time have significant side effects. In recent years, photothermal therapy (PTT) has been widely studied in tumor treatment due to its good therapeutic effects, low side effects, and non-invasiveness. The key to PTT is photothermal agents (PTAs), which can undergo photothermal conversion under specific wavelengths of near-infrared (NIR) light irradiation, achieving thermal ablation of tumors. Metal organic frameworks (MOFs) are coordination polymers formed by self-assembling organic ligands and transition metal ions. They have high surface area, high porosity, and easy functionalization, making them a potential material for tumor photothermal therapy. Load PTAs through MOFs, PTT efficacy can be enhanced, presenting significant potential in the field of PTT. This article reviews the research progress on the combination of commonly used PTAs and MOFs in PTT and discusses the issues that need to be addressed for the application of MOFs in PTT. This article reviews the research progress on the combination of commonly used PTAs and MOFs in PTT and discusses the issues that need to be addressed for the application of MOFs in PTT. [Display omitted] • An overview about the recent developments in the MOFs on PTT. • Sensing applications of MOFs loaded photothermal agents is presented in detail. • The therapy mechanism had been discussed. [ABSTRACT FROM AUTHOR]

Sonodynamic therapy (SDT) is a new treatment method combining low-intensity ultrasound with sono-sensitizers, which has the advantages of non-invasiveness as well as low side effects, and has a very broad application prospect in antitumor clinics because of its high penetration ability to tissues and hence can be used to treat some deep lesions. Nevertheless, the clinical application of SDT is seriously affected by factors such as hypoxia of tumor microenvironment and low bioavailability of sono-sensitizers, and its in vivo tumor suppression efficiency is far from the desired expected effect. Metal-organic frameworks (MOFs) are new hybrid crystalline porous materials synthesized using metal nodes and organic ligands. With a large specific surface area, adjustable and modifiable structures, good biodegradability, high drug loading, controlled drug release, and strong targeting, MOF can serve as a powerful multifunctional platform to effectively solve some of the problems faced in SDT. In this review, we present different types of MOFs as super-efficient sono-sensitizers carriers and the latest research progress in the area of MOFs having sonosensitizers as organic ligands to enhance SDT, using different types of sono-sensitizers as an entry point. Finally, we summarize some pertinent issues in ultrasound dynamics in potential practice and the future development prospect of ultrasound dynamics. In this review, we present different types of MOFs as super-efficient sonosensitizers carriers and MOFs with sonosensitizers as organic ligands to enhance SDT, using different types of sonosensitizers as an entry point. Finally, we summarize some pressing issues in ultrasound dynamics in clinical practice and look into the future development of ultrasound dynamics. [Display omitted] • Several of MOFs as super-efficient sonosensitizers carriers and MOFs with sonosensitizers were concluded. • The possible SDT mechanism was proposed. • The current promising application and its challenge in SDT were suggested. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Urinary tract infection, urinary frequency, urgency, urodynia and haemorrhage are common post‐operative complications of thulium laser resection of the prostate (TmLRP). Our study mainly focuses on the role of finasteride in prostate wound healing through AR signalling. Materials and methods: TmLRP beagles were randomly distributed into different treatment groups. Serum and intra‐prostatic testosterone and DHT level were determined. Histological analysis was conducted to study the re‐epithelialization and inflammatory response of the prostatic urethra in each group. We investigated the role of androgen in proliferation and inflammatory response in prostate. In addition, the effects of TNF‐α on prostate epithelium and stromal cells were also investigated. Results: Testosterone and DHT level increased in testosterone group and DHT decreased in finasteride group. Accelerated wound healing of prostatic urethra was observed in the finasteride group. DHT suppressed proliferation of prostate epithelium and enhanced inflammatory response in prostate. We confirmed that DHT enhanced macrophages TNF‐α secretion through AR signalling. TNF‐α suppressed proliferation of prostate epithelial cells and retarded cell migration. TNF‐α also played a pivotal role in suppressing fibroblasts activation and contraction. Conclusion: Testosterone treatment repressed re‐epithelialization and wound healing of prostatic urethra. Finasteride treatment may be an effective way to promote prostate re‐epithelialization. [ABSTRACT FROM AUTHOR]

Quorum quenching (QQ) is a novel anti-biofouling strategy for membrane bioreactors (MBRs) used in wastewater treatment. However, actual operation of QQ-MBR systems for wastewater treatment needs to be systematically studied to evaluate the comprehensive effects of QQ on wastewater treatment engineering applications. In this study, a novel QQ strain, Acinetobacter pittii HITSZ001, was encapsulated and applied to a MBR system to evaluate the effects of this organism on real wastewater treatment. To verify the effectiveness of immobilized QQ beads in the MBR system, we examined the MBR effluent quality and sludge characteristics. We also measured the extracellular polymeric substances (EPS) and soluble microbial products (SMP) in the system to determine the effects of the organism on membrane biofouling inhibition. Additionally, changes in microbial communities in the system were analyzed by high-throughput sequencing. The results indicated that Acinetobacter pittii HITSZ001 is a promising strain for biofouling reduction in MBRs treating real wastewater, and that immobilization does not affect the biofouling control potential of QQ bacteria. [ABSTRACT FROM AUTHOR]

Background: Overwhelming evidences suggest oxidative stress is a major cause of sperm dysfunction and male infertility. Zinc is an important non-enzymatic antioxidant with a wide range of biological functions and plays a significant role in preserving male fertility. Notably, zinc trafficking through the cellular and intracellular membrane is mediated by specific families of zinc transporters, i.e., SLC39s/ZIPs and SLC30s/ZnTs. However, their expression and function were rarely evaluated in the male germ cells. The aim of this study is to determine and characterize the crucial zinc transporter responsible for the maintenance of spermatogenesis. Methods: The expression patterns of all 14 ZIP members were characterized in the mouse testis. qRT-PCR, immunoblot and immunohistochemistry analyses evaluated the ZIP12 gene and protein expression levels. The role of ZIP12 expression was evaluated in suppressing the sperm quality induced by exposure to an oxidative stress in a spermatogonia C18–4 cell line. Zip12 RNAi transfection was performed to determine if its downregulation altered cell viability and apoptosis in this cell line. An obese mouse model fed a high-fat-diet was employed to determine if there is a correlation between changes in the ZIP12 expression level and sperm quality. Results: The ZIP12 mRNA and protein expression levels were higher than those of other ZIP family members in both the mouse testis and other tissues. Importantly, the ZIP12 expression levels were very significantly higher in both mice and human spermatogonia and spermatozoa. Moreover, the testicular ZIP12 expression levels significantly decreased in obese mice, which was associated with reduced sperm zinc content, excessive sperm ROS generation, poor sperm quality and male subfertility. Similarly, exposure to an oxidative stress induced significant declines in the ZIP12 expression level in C18–4 cells. Knockdown of ZIP12 expression mediated by transfection of a ZIP12 siRNA reduced both the zinc content and viability whereas apoptotic activity increased in the C18–4 cell line. Conclusions: The testicular zinc transporter ZIP12 expression levels especially in spermatogonia and spermatozoa are higher than in other tissues. ZIP12 may play a key role in maintaining intracellular zinc content at levels that reduce the inhibitory effects of rises in oxidative stress on spermatogonia and spermatozoa viability during spermatogenesis which help counteract declines in male fertility. [ABSTRACT FROM AUTHOR]

Background: Androgen deprivation therapy (ADT) is the backbone of therapy for advanced prostate cancer (PCa). Despite the good initial response, castration resistance and metastatic progression will inevitably occur. Cancer-associated fibroblasts (CAFs) may be implicated in promoting metastasis of PCa after ADT. Our aim is to investigate the role and mechanism of CAFs-derived exosomes involving in metastasis of PCa after ADT. Methods: PCa cells were co-cultured with exosomes derived from 10 nM dihydrotestosterone (DHT)-treated (simulating the high androgen level of prostate cancer microenvironment) or ethanol (ETOH) -treated (simulating the castration level of prostate cancer microenvironment after ADT) CAFs, and their migration and invasion differences under castration condition were examined both in vitro and in vivo. The miRNA profiles of exosomes derived from DHT-treated CAFs and matched ETOH-treated CAFs were analysed via next generation sequencing. The transfer of exosomal miR-146a-5p from CAFs to PCa cells was identified by fluorescent microscopy. The function and direct target gene of exosomal miR-146a-5p in PCa cells were confirmed through Transwell assays, luciferase reporter, and western blot. Results: Compared with DHT-treated CAFs, exosomes derived from ETOH-treated CAFs dramatically increased migration and invasion of PCa cells under castration condition. MiR-146a-5p level in exosomes from ETOH-treated CAFs was significantly reduced. The loss of miR-146a-5p may strengthen the epithelial-mesenchymal transition (EMT) to accelerate cancer cells metastasis by modulating epidermal growth factor receptor (EGFR)/ERK pathway. Conclusions: CAFs-derived exosomal miR-146a-5p confers metastasis in PCa cells under ADT through the EGFR/ERK pathway and it may present a new treatment for PCa. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the clinical implications of CD3+CD69+ T-cells and CD8+CD28+ T-cells in the peripheral blood of patients prior to radical prostatectomy.Materials and Methods: A total of 91 prostate cancer (PCa) patients and 50 benign prostatic hyperplasia (BPH) patients were enrolled from January 2016 to December 2017. The proportions of CD3+CD69+ T-cells and CD8+CD28+ T-cells in the peripheral blood of PCa and BPH patients were detected by flow cytometry, and the association of these T-cell populations with pathological Grade Group and pathological TNM classification was evaluated. Data analysis was performed with SAS version 9.4 software.Results: The proportions of CD3+CD69+ and CD8+CD28+ T-cells in peripheral blood were higher in PCa patients than those in BPH patients. Multivariate analysis identified a higher CD3+CD69+ T-cell proportion as a risk factor for PCa (odds ratio (OR) = 4.783, P = 0.0013), but the diagnostic efficacy of the CD3+CD69+ T-cell proportion (area under the curve (AUC)=0.6833, P = 0.0003) for PCa was still inferior to that of the tPSA level (AUC=0.7531, P < 0.0001). The AUCs for CD3+CD69+ T-cell and CD8+CD28+ T-cell proportions for PCa were 0.6959 (P = 0.0372) and 0.6935 (P = 0.0395), respectively, among men with tPSA levels of 4.0-10.0 ng/mL. A lower CD3+CD69+ T-cell proportion was associated with higher pathological Grade Group (P=0.0074).Conclusion: The proportions of CD3+CD69+ T-cells and CD8+CD28+ T-cells in peripheral blood are potential diagnostic indicators for PCa. The preoperative proportion of CD3+CD69+ T-cells in peripheral blood may have prognostic value in terms of the pathological Grade Group in PCa. [ABSTRACT FROM AUTHOR]

Objectives Previously, we found that long intergenic non-coding RNA-p21 (linc RNA-p21) inhibited the development of human prostate cancer. However, the underlying molecular mechanisms are poorly understood. Here, we attempted to investigate the downstream targets of linc RNA-p21 in prostate cancer. Materials and methods Expression of lincRNA-p21 and PKM2 was determined by qRT- PCR and Western blot. Lentivirus expressing shPKM2 or shCtrl was used to explore the role of PKM2 on the enhanced cell proliferation and glycolysis of linc RNA-p21-silenced prostate cancer cells. A xenograft mouse model was performed to investigate the effect of PKM2 suppression, glycolytic or mammalian target of rapamycin (mTOR) inhibitor on the tumorigenic capacity of lincRNA-p21-silenced prostate cancer cells. Results We revealed that linc RNA-p21 silencing in DU145 and LNCaP cells induced up-regulation of PKM2 and activation of glycolysis, which could be reversed by PKM2 knockdown or rapamycin treatment. We also found that the proliferation and tumorigenesis of linc RNA-p21-silenced prostate cancer cells were significantly inhibited after knocking down PKM2. 3-bromopyruvate (3-Brpa) or rapamycin treatment largely decreased the tumour burden. Importantly, PKM2 expression was inversely correlated with the linc RNA-p21 level and the survival of prostate cancer patients. Conclusions We demonstrated that linc RNA-p21 blunted the prostate cancer cell proliferation and tumorigenic capacity through down-regulation of PKM2. Therefore, targeting PKM2 or glycolysis might be a therapeutic strategy in prostate cancer patients with lowly expressed linc RNA-p21. [ABSTRACT FROM AUTHOR]

Objectives Prostate cancer is one of the most frequent malignancies in men, worldwide, although its underlying mechanisms are not fully understood. Long non-coding RNAs participate in development of human cancers. In this invetsigation, we aimed to study the roles of linc RNA-p21 in development of human prostate cancer. Materials and methods Expression of linc RNA-p21 was assessed by real-time PCR in cell lines and in human tissues. Lentivirus carrying sh-linc RNA-p21, linc RNA-p21 or control constructs were used to determine their effects on cell proliferation and apoptosis. A mouse xenograft model was employed to explore the functions of linc RNA-p21 on cancer cell population growth in vivo. Relationships between p53 downstream genes and linc RNA-p21 levels were explored by real-time PCR, western blotting and chromatin immunoprecipitation. Results Linc RNA-p21 was found to be down-regulated in human prostate cancer, and low levels of linc RNA-p21 correlated with high disease stage and prediction of poor survival. We further showed that linc RNA-p21 inhibited prostate cancer cell proliferation and colony formation in vitro and reduced rate of prostate cancer cell population growth in vivo. Study of mechanisms involved revealed that linc RNA-p21 promoted apoptosis and induced expression of p53 downstream genes by regulating p53 binding to their promoters. Finally, we showed that expression of p53 downstream genes was reduced in the malignant prostate tissues, which correlated with linc RNA-p21 level. Conclusions Our findings indicated that linc RNA-p21 inhibited development of human prostate cancer partly by regulating p53 downstream gene expression and partly by apoptotic activation. [ABSTRACT FROM AUTHOR]

Quorum quenching (QQ) has proven its potential as an innovative approach for biofouling control in membrane bioreactor (MBR) for wastewater treatment. In this study, a novel quorum-quenching bacterium, Acinetobacter pittii HITSZ001, was isolated from activated sludge. In contrast to previous studies, in which QQ bacteria were directly applied in the MBR system, in this investigation, this strain was co-cultured with Pseudomonas aeruginosa to illustrate the inhibitory effect of the QQ strain on the key genes involved in biofilm formation. The types of QQ enzymes secreted by A. pittii HITSZ001 and its functional ahlm gene was also identified. To better apply this strain, it was encapsulated in the QQ beads with great activities, which could well adapt to a complex real activated sludge environment and effectively controlled biofilm formation on the membrane. The results of this study suggest that A. pittii HITSZ001 represents a novel and promising strain for biofilm mitigation to promote MBR performance and that it would be economically and technically feasible to expand biofouling control with this strain to plant-scale MBRs and similar environmental engineering systems. [Display omitted] • A quorum quenching strain was isolated and its mechanism was identified. • The QS genes in Pseudomonas aeruginosa were downregulated by QQ strain. • The encapsulated QQ strain can inhibit biofilm formation effectively. • A new biological method to detect the quantity of AHL was improved. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer is one of the most common malignancies. Increasing evidence suggested that endothelial cells may contribute to prostate cancer progression and metastasis. Most recently, autophagy has been proposed to plays a significant role in tumorigenesis and metastasis. Also, it is reported that downregulation of androgen receptor (AR) induces autophagy in prostate cancer cells. However, the underlying mechanisms remain unclear. Here, we aim to explore the role and mechanisms of endothelial cell in prostate cancer progression. Methods: The coculture system was established to test the effect of endothelial cells on prostate cancer cells. We performed antibody array and ELISA were used to profile the cytokine expression pattern of endothelial cells in supernatant. Western blot and RT-PCR were used to determine the mechanism by endothelial cells to promote invasion ability of prostate cancer cells. Maraviroc and chloroquine were used to block the CCL5/CCR5 and autophagy pathway respectively. Orthotopic xenograft mouse models and drug treatment study were conducted to determine the role of endothelial cells in promoting metastatic potential in vivo. Results: We use CPRC prostate cancer model and demonstrate that endothelial cells secrete large amount of CCL5 and induces autophagy by suppressing AR expression in prostate cancer cell lines. Consequently, elevated autophagy accelerates focal adhesions proteins disassembly and promoted prostate cancer invasion. Inhibition of both CCL5/CCR5 signaling and autophagy significantly reduces metastasis in vivo. Conclusions: Together, our data establish the function for endothelial cells in tumor metastasis and propose new drug target for mCRPC. [ABSTRACT FROM AUTHOR]