A Comparative Study of Inhibition Function between High-Intensity Interval Training and Moderate-Intensity Continuous Training in Healthy People: A Systematic Review with Meta-Analysis.

Meta-analysis was used to compare the effects of two interventions, high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), on inhibition in executive function in healthy people, providing some theoretical basis for exercise practice and health interventions. We searched the PubMed, Science Direct, Web Of science, Cochrane, and CNKI databases for relevant articles on the inhibition function effects of HIIT and MICT in healthy populations for the period of library construction to 15 September 2022. The basic information of the screened literature was organized and summarized using Excel. Statistical analysis of the correct rate and response time indicators of the inhibition function in the HIIT and MICT groups was performed using Review Manager 5.3 analysis software. A total of 285 subjects from 8 studies were included in this study, the number of HIIT subjects was 142, the number of MICT subjects was 143, including teenagers, young adults, and the elderly. Eight studies included response time, and four included correct rate and response time. The standardized mean difference (SMD) for correct rate inhibition function in the HIIT and MICT groups was 0.14, 95% CI (-0.18, 0.47), SMD at response time was 0.03, 95% CI (-0.20, 0.27). In addition, no significant differences were found between the two exercise modalities in either the intervention period or the population receiving the intervention. Both HIIT and MICT could improve inhibition function in healthy people, but there was no significant difference in the improvement effect between them. It is hoped that this study can provide some references for people's choice of health intervention methods and clinical practice.

[Study on the EEG functional brain connectivity characteristics of college students with depression].

The aim of the present study was to explore the changes in some functional connectivity in the resting-state electroencephalogram (EEG) based functional brain network of depressed college students, and to understand the brain regions involved in the onset of depression and the electrophysiological activity of subcortical nerve cells, hoping to provide additional information for the diagnosis of depression. Twenty female college students with depressive symptoms were selected according to the Beck Depression Inventory-II (BDI-II) and the Self-rating Depression Scale (SDS). The EEG information of 20 female college students under resting-state was collected by using a 32-conduction EEG acquisition system (Neuroscan). Then Pearson correlation analysis, coherence analysis, phase locking value analysis, phase lag index analysis and weighted phase lag index analysis were used to construct the resting-state brain functional network. The results showed that, compared with the normal group, the depression group exhibited significantly increased correlation in θ and ß bands of EEG (P < 0.05), and extremely significantly increased in α band (P < 0.01). Among them, the coherence in α and ß bands was significantly increased (P < 0.05), mainly concentrated in the left hemisphere frontal lobe and temporal lobe region. The phase locking value in θ, α and ß bands was significantly increased (P < 0.05), mainly concentrated in the prefrontal region and the left hemisphere from the frontal region to the temporal region, and the connectivity in α band was the most obvious. Correlation analysis showed a significant positive correlation between indicators of differential functional connectivity (coherence and phase locking value) and BDI-II scores in the depression group, and the receiver operating characteristics (ROC) curve indicated a high specificity of 85% for the differential indicators. These results suggest that the abnormal brain function of the depressed college students is related to the change of functional connectivity in the left hemisphere, especially α frequency band in the frontal region, which is of great significance for the diagnosis of depression in the future.

Transcranial ultrasound neuromodulation induces neuronal correlation change in the rat somatosensory cortex.

Objective.Transcranial focused ultrasound (tFUS) is a neuromodulation technique which has been the focus of increasing interest for noninvasive brain stimulation with high spatial specificity. Its ability to excite and inhibit neural circuits as well as to modulate perception and behavior has been demonstrated, however, we currently lack understanding of how tFUS modulates the ways neurons interact with each other. This understanding would help elucidate tFUS's mechanism of systemic neuromodulation and allow future development of therapies for treating neurological disorders.Approach.In this study, we investigate how tFUS modulates neural interaction and response to peripheral electrical limb stimulation through intracranial multi-electrode recordings in the rat somatosensory cortex. We deliver ultrasound in a pulsed pattern to induce frequency dependent plasticity in a manner similar to what is found following electrical stimulation.Main Results.We show that neural firing in response to peripheral electrical stimulation is increased after ultrasound stimulation at all frequencies, showing tFUS induced changes in excitability of individual neuronsin vivo. We demonstrate tFUS sonication repetition frequency dependent pairwise correlation changes between neurons, with both increases and decreases observed at different frequencies.Significance.These results extend previous research showing tFUS to be capable of inducing synaptic depression and demonstrate its ability to modulate network dynamics as a whole.

Frailty is associated with 90-day unplanned readmissions and death in patients with heart failure: A longitudinal study in China.

BACKGROUND: Frailty has been reported to be significantly associated with adverse health outcomes in people with heart failure (HF). OBJECTIVES: To explore the potential effects of frailty on unplanned readmissions and death in people with HF patients aged 18 years or older. METHODS: 342 HF patients aged 18 years or older from the heart centers of two different tertiary care hospitals located in northwest of China were enrolled between July and December 2020. Frailty was assessed by the Tilburg Frailty Indicator. The patients were followed for unplanned readmissions, and all-cause mortality at 30, 60, as well as 90 days after discharge. Multivariate cox regression models were used to analyze the effects of frailty on 90-day unplanned readmission and death in the patients with HF. RESULTS: Frailty prevalence was 54.7% among 342 HF patients, with a mean age of 64.65 ± 11.90 years. It was found that compared to non-frailty HF patients, the frailty HF patients were older and displayed higher systolic blood pressure, longer duration of HF, more severe cognitive function, and more comorbidities (P < 0.05). On the contrary, the patients in the frail group had a higher incidence of unplanned readmission (73.1% vs. 26.9%, χ2 = 18.87, P < 0.01) and death (100% vs. 0%, χ2 = 6.94, P < 0.01) than those in the non-frail group. Multivariate cox regression analysis showed that frailty could serve as an independent risk factor for 90-day unplanned readmission (HR = 1.469, 95% CI 1.318-1.637, P < 0.01) and 90-day death (HR=2.270, 95% CI 1.091-4.726, P < 0.01) in the patients with HF. CONCLUSION: Frailty can act as an independent predictor of unplanned readmission and death 90-day after discharge in HF patients aged 18 years or older.

Transcranial focused ultrasound induces sustained synaptic plasticity in rat hippocampus.

Transcranial focused ultrasound (tFUS) neuromodulation provides a promising emerging non-invasive therapy for the treatment of neurological disorders. Many studies have demonstrated the ability of tFUS to elicit transient changes in neural responses. However, the ability of tFUS to induce sustained changes need to be carefully examined. In this study, we use the long-term potentiation/long term depression (LTP/LTD) model in the rat hippocampus, the medial perforant path (mPP) to dentate gyrus (DG) pathway, to explore whether tFUS is capable of encoding frequency specific information to induce plasticity. Single-element focused transducers were used for tFUS stimulation with ultrasound fundamental frequency of 0.5 MHz and nominal focal distance of 38 mm tFUS stimulation is directed to mPP. Measurement of synaptic connectivity is achieved through the slope of field excitatory post synaptic potentials (fEPSPs), which are elicited using bipolar electrical stimulation electrodes and recorded at DG using extracellular electrodes to quantify degree of plasticity. We applied pulsed tFUS stimulation with total duration of 5 min, with 5 levels of pulse repetition frequencies each administered at 50 Hz sonication frequency at the mPP. Baseline fEPSP is recorded 10 min prior, and 30+ minutes after tFUS administration. In N = 16 adult wildtype rats, we observed sustained depression of fEPSP slope after 5 min of tFUS focused at the presynaptic field mPP. Across all PRFs, no significant difference in maximum fEPSP slope change was observed, average tFUS induced depression level was observed at 19.6%. When compared to low frequency electrical stimulation (LFS) of 1 Hz delivered to the mPP, the sustained changes induced by tFUS stimulation show no statistical difference to LFS for up to 24 min after tFUS stimulation. When both the maximum depression effects and the duration of sustained effects are both taken into account, PRF 3 kHz can induce significantly larger effects than other PRFs tested. tFUS stimulation is measured with a spatial-peak pressure amplitude of 99 kPa, translating to an estimation of 0.43 °C temperature increase when assuming no loss of heat. The results suggest the ability of tFUS to encode sustained changes in synaptic connectivity through mechanism which are unlikely to involve thermal changes.

Gut Microbiota in Patients with Polycystic Ovary Syndrome: a Systematic Review.

Polycystic ovary Syndrome (PCOS) is one of the most popular diseases that cause menstrual dysfunction and infertility in women. Recently, the relationships between the gastrointestinal microbiome and metabolic disorders such as obesity, type 2 diabetes and PCOS have been discovered. However, the association between the gut microbiome and PCOS symptoms has not been well established. We systematically reviewed existing studies comparing gut microbial composition in PCOS and healthy volunteers to explore evidence for this association. A systematic search was carried out in PubMed, Embase, Cochrane Library, and Web of Science from inception to May 26, 2020, for all original cross-sectional, cohort, or case-control studies comparing the fecal microbiomes of patients with PCOS with microbiomes of healthy volunteers (controls). The primary outcomes were differences in specific gut microbes between patients with PCOS and controls. The search identified 256 citations; 10 studies were included. The total population study of these articles consists of 611 participants (including PCOS group and healthy controls group). Among the included 10 studies, nine studies compared α-diversity, and six studies demonstrated that α-diversity has a significant reduction in PCOS patients. Seven of them reported that there was a significant difference of ß-diversity composition between healthy controls groups and PCOS patients. The most common bacterial alterations in PCOS patients included Bacteroidaceae, Coprococcus, Bacteroides, Prevotella, Lactobacillus, Parabacteroides, Escherichia/Shigella, and Faecalibacterium prausnitzii. No consensus has emerged from existing human studies of PCOS and gut microbiome concerning which bacterial taxa are most relevant to it. In this systematic review, we identified specific bacteria associated with microbiomes of patients with PCOS vs controls. Higher level of evidence is needed to determine whether these microbes are a product or cause of PCOS.

Investigation of displacement of intracranial electrode induced by focused ultrasound stimulation.

Transcranial focused ultrasound (tFUS) is an emerging neuromodulation technique to modulate brain activity non-invasively with high spatial specificity and focality. Given the influence of tFUS on brain activity, combining tFUS with multi-channel intracranial electrophysiological recordings enables monitoring of the activity of large populations of neurons with high temporal resolution. However, the physical interactions between tFUS and the electrode may affect a reliable assessment of neuronal activity, which remains poorly understood. In this paper, high-frequency ultrasound (HFUS) system was developed and integrated into tFUS neuromodulation system. The performance of the HFUS-based displacement tracking and analysis was evaluated by the theoretical analysis in the literature. The effects of various pressure levels on the displacements of the silicon-based microelectrode array in ex vivo brain tissue were investigated. The developed approach was capable of tracking and measuring the motion of a solid sphere in a tissue-mimicking phantom and measured displacements were comparable to theoretical predictions. The significant changes in the averaged peak displacements of the microelectrode array in ex vivo brain were observed with a pulse duration of 200 µs and a peak-to-peak pressure from 131 kPa at a center frequency of 500 kHz compared with the values from the negative control group. The present results demonstrate the relationship between several pressure levels and displacements of the microelectrode array in ex vivo brain through the developed approach. This approach can be used to determine a vibration-free threshold of ultrasound parameters in multi-channel intracranial recordings for a reliable assessment of electrophysiological activities of living neurons.

Intrinsic functional neuron-type selectivity of transcranial focused ultrasound neuromodulation.

Transcranial focused ultrasound (tFUS) is a promising neuromodulation technique, but its mechanisms remain unclear. We hypothesize that if tFUS parameters exhibit distinct modulation effects in different neuron populations, then the mechanism can be understood through identifying unique features in these neuron populations. In this work, we investigate the effect of tFUS stimulation on different functional neuron types in in vivo anesthetized rodent brains. Single neuron recordings were separated into regular-spiking and fast-spiking units based on their extracellular spike shapes acquired through intracranial electrophysiological recordings, and further validated in transgenic optogenetic mice models of light-excitable excitatory and inhibitory neurons. We show that excitatory and inhibitory neurons are intrinsically different in response to ultrasound pulse repetition frequency (PRF). The results suggest that we can preferentially target specific neuron types noninvasively by tuning the tFUS PRF. Chemically deafened rats and genetically deafened mice were further tested for validating the directly local neural effects induced by tFUS without potential auditory confounds.

Effects of nurse-led web-based interventions on people with type 2 diabetes mellitus: A systematic review and meta-analysis.

INTRODUCTION: Diabetes mellitus is an expanding global health problem. Currently, the home management of diabetes is mainly led by a multidisciplinary team based on telemedicine. However, the role nurses play in it remains inconclusive. This study aimed to investigate the effectiveness of nurse-led web-based intervention on glycated haemoglobin, blood pressure and lipid profile in patients with type 2 diabetes. METHODS: An exhaustive systematic literature search was undertaken using the following databases: PubMed, Web of Science, Embase, The Cochrane Central Register of Controlled Trials and CINAHL. Two investigators independently extracted data and assessed the quality of the studies by examining the risk of bias and using Modified Jadad Score system. We conducted a meta-analysis of randomized controlled trials that had been published from inception to July 2020, using Review Manager 5.3. RESULTS: Eleven randomized controlled trials were selected that included 2063 participants. Meta-analyses results indicated significant effects on not only glycated haemoglobin (pooled mean difference (MD) = -0.40, 95% confidence interval (CI): -0.5 to -0.26, p < 0.00001), but also on systolic blood pressure (pooled MD = -1.91, 95% CI: -3.73 to -0.09, p = 0.04) and low density lipoprotein (pooled standardized MD = -0.29, 95% CI: -0.44 to -0.15, p < 0.0001). There were no effects of nurse-led web-based intervention on fasting blood glucose, diastolic blood pressure, high density lipoprotein, body mass index and triglycerides. DISCUSSION: Nurse-led web-based intervention is a promising way to complement routine clinical care. However, the specific intervention content and intervention media still need to carry out large-scale well-designed randomized controlled trials. Systematic review registration: PROSPERO CRD 42020204565.

Therapeutic Ultrasound Triggered Silk Fibroin Scaffold Degradation.

A patient's capacity for tissue regeneration varies based on age, nutritional status, disease state, lifestyle, and gender. Because regeneration cannot be predicted prior to biomaterial implantation, there is a need for responsive biomaterials with adaptive, personalized degradation profiles to improve regenerative outcomes. This study reports a new approach to use therapeutic ultrasound as a means of altering the degradation profile of silk fibroin biomaterials noninvasively postimplantation. By evaluating changes in weight, porosity, surface morphology, compressive modulus, and chemical structure, it is concluded that therapeutic ultrasound can trigger enhanced degradation of silk fibroin scaffolds noninvasively. By removing microbubbles on the scaffold surface, it is found that acoustic cavitation is the mechanism responsible for changing the degradation profile. This method is proved to be safe for human cells with no negative effects on cell viability or metabolism. Sonication through human skin also effectively triggers scaffold degradation, increasing the clinical relevance of these results. These findings suggest that silk is an ultrasound-responsive biomaterial, where the degradation profile can be adjusted noninvasively to improve regenerative outcomes.

Transcranial Focused Ultrasound Enhances Sensory Discrimination Capability through Somatosensory Cortical Excitation.

Low-intensity transcranial focused ultrasound (tFUS) has emerged as a non-invasive brain neuromodulation tool with high spatial specificity. Previous studies attributed tFUS-enhanced sensory performance to the ultrasound-induced inhibitory neural effects. However, to date there is no direct evidence validating the neural mechanism underlying ultrasound-mediated somatosensory enhancement. In this study, healthy human subjects (N = 9) were asked to perform tactile vibration frequency discrimination tasks while tFUS was directed onto the primary somatosensory cortex. During this task, we simultaneously recorded 64-channel electroencephalography (EEG) signals and investigated the brain responses at both EEG sensors and source domains by means of electrophysiological source imaging (ESI). The behavioral results indicated that the subjects' discrimination ability was improved by tFUS with an increased percentage of correct responses. EEG and ESI results revealed that tFUS neuromodulation was able to improve sensory discrimination capability through excitatory effects at the targeted sensory cortex.

Impacts of frailty on health care costs among community-dwelling older adults: A meta-analysis of cohort studies.

BACKGROUND: The demands for health care services from the frail elderly individuals in the community continue to increase, which will exert a tremendous burden on health care costs. However, little is known regarding the magnitude of these impacts. In this study, we performed a systematic review and meta-analysis of the evidence to explore the impact of frailty on health care costs among community-dwelling older adults. MATERIALS AND METHODS: Relevant published articles were searched from PubMed, Embase, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journal Full-text Database (VIP), Wanfang Database, Chinese Biomedical Literature Database (CBM), and the reference lists of articles. Published cohort or cross-sectional studies assessing the impacts of frailty on health care costs among community-dwelling older adults were identified (to June 2020). The outcomes on health care costs before and after baseline were stratified by frailty status. RESULTS: A total of 7 cohort studies comprised of a total of 3,750,611 participants were included in our study. Our analyses showed that: (1) compared with the robust group, health care costs increased by $79-13,423.83 (standardized mean difference, SMD = 0.22, 95% Confidence interval, 95% CI, 0.22-0.22; P < 0.00001) in the pre-frail elderly and by $616-32,549.96 (SMD = 0.55, 95% CI, 0.44-0.67; P < 0.00001) in the frail elderly in the community. A significantly higher in the increase of health care costs was observed in the frail group compared with the pre-frail group(SMD = 0.35, 95% CI, 0.19-0.51; P < 0.0001); (2) the frailty phenotype components increased the health care costs of the elderly in community (weight loss: $1,630-6,209, SMD = 0.43, 95% CI, 0.17-0.69; P = 0.001; weakness: $275-7,586, SMD = 0.24, 95% CI, 0.08-0.40; P = 0.001; exhaustion: $1,545-10,559, SMD = 0.31, 95% CI, 0.13-0.49; P = 0.0006; slowness: $352-1,1891, SMD = 0.40, 95% CI = 0.14-0.65; P = 0.003; low physical activity: $512-3,459, SMD = 0.26, 95% CI, 0.16-0.36; P < 0.00001); (3) the increase in the frailty index was parallel with the increase in health care costs by $12,363-21,066 (SMD = 0.41, 95% CI, 0.29-0.53; P < 0.00001). CONCLUSIONS AND IMPLICATIONS: This study revealed the adverse economic impacts of frailty status, frailty phenotype components, and frailty index on health care costs in community-dwelling older adults. Future research is warranted to investigate costs incurred by interventions to improve frailty, which will provide further insights into additional health care costs due to frailty.

Transcranial Focused Ultrasound Neuromodulation of Voluntary Movement-Related Cortical Activity in Humans.

OBJECTIVE: Transcranial focused ultrasound (tFUS) is an emerging non-invasive brain stimulation tool for safely and reversibly modulating brain circuits. The effectiveness of tFUS on human brain has been demonstrated, but how tFUS influences the human voluntary motor processing in the brain remains unclear. METHODS: We apply low-intensity tFUS to modulate the movement-related cortical potential (MRCP) originating from human subjects practicing a voluntary foot tapping task. 64-channel electroencephalograph (EEG) is recorded concurrently and further used to reconstruct the brain source activity specifically at the primary leg motor cortical area using the electrophysiological source imaging (ESI). RESULTS: The ESI illustrates the ultrasound modulated MRCP source dynamics with high spatiotemporal resolutions. The MRCP source is imaged and its source profile is further evaluated for assessing the tFUS neuromodulatory effects on the voluntary MRCP. Moreover, the effect of ultrasound pulse repetition frequency (UPRF) is further assessed in modulating the MRCP. The ESI results show that tFUS significantly increases the MRCP source profile amplitude (MSPA) comparing to a sham ultrasound condition, and further, a high UPRF enhances the MSPA more than a low UPRF does. CONCLUSION: The present results demonstrate the neuromodulatory effects of the low-intensity tFUS on enhancing the human voluntary movement-related cortical activities evidenced through the ESI. SIGNIFICANCE: This work provides the first evidence of tFUS enhancing the human endogenous motor cortical activities through excitatory modulation.

Menopause and frailty: a scoping review.

IMPORTANCE AND OBJECTIVE: Frailty refers to the decline in physiological reserve capacity caused by the deterioration of multiple physiological systems (brain, endocrine system, immune system, and skeletal muscle), leading to increased vulnerability and decreased stress capacity. Women have a higher prevalence of frailty than men, although the epidemiological factors underlying this phenomenon are not fully understood. Menopause and menopause-related characteristics may be among the contributing factors. Hence, the purpose of this scoping review was to explore the relationship between menopause and frailty. We attempted to summarize information such as the age that menopause occurs, years since menopause, types of menopause, and hormones and inflammatory markers of frailty among postmenopausal women. METHODS: PubMed, EMBASE, The Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature and Web of Science, the China National Knowledge Infrastructure, the China Biomedical Literature Service System, Wanfang Database and the WeiPu (VIP) Database were searched from inception until April 3, 2019. Supplementary searches of the references, cited documents, and similar documents of the included literature were also carried out. DISCUSSION AND CONCLUSIONS: Of 762 papers identified, 15 articles matching the criteria were included. The prevalence of frailty among postmenopausal women ranged from 5.9% to 57.3%. Existing studies suggest that menopause is associated with frailty. Early menopause, hysterectomy, low-free testosterone levels, and high C-reactive protein levels may increase the likelihood of frailty among postmenopausal women. Few original studies have explored the relationship between estrogen and frailty and the results of these studies are conflicting. Changes in hormone and inflammatory cytokine levels may mediate frailty among postmenopausal women. More in-depth research would be required to better understand the physiological and etiological mechanisms of the occurrence of frailty among postmenopausal women.

Neuromodulation Management of Chronic Neuropathic Pain in The Central Nervous system.

Neuromodulation is becoming one of the clinical tools for treating chronic neuropathic pain by transmitting controlled physical energy to the pre-identified neural targets in the central nervous system. Its nature of drug-free, non-addictive and improved targeting have attracted increasing attention among neuroscience research and clinical practices. This article provides a brief overview of the neuropathic pain and pharmacological routines for treatment, summarizes both the invasive and non-invasive neuromodulation modalities for pain management, and highlights an emerging brain stimulation technology, transcranial focused ultrasound (tFUS) with a focus on ultrasound transducer devices and the achieved neuromodulation effects and applications on pain management. Practical considerations of spatial guidance for tFUS are discussed for clinical applications. The safety of transcranial ultrasound neuromodulation and its future prospectives on pain management are also discussed.

Correction: Neurotensin and its receptors mediate neuroendocrine transdifferentiation in prostate cancer.

A correction to this paper has been published and can be accessed via a link at the top of the paper.

Neurotensin and its receptors mediate neuroendocrine transdifferentiation in prostate cancer.

Castration-resistant prostate cancer (CRPC) with neuroendocrine differentiation (NED) is a lethal disease for which effective therapies are urgently needed. The mechanism underlying development of CRPC with NED, however, remains largely uncharacterized. In this study, we explored and characterized the functional role of neurotensin (NTS) in cell line and animal models of CRPC with NED. NTS was acutely induced by androgen deprivation in animal models of prostate cancer (PCa) and activated downstream signaling leading to NED through activation of neurotensin receptor 1 (NTSR1) and neurotensin receptor 3 (NTSR3), but not neurotensin receptor 2 (NTSR2). Our findings also revealed the existence of a CK8+/CK14+ subpopulation in the LNCaP cell line that expresses high levels of both NTSR1 and NTSR3, and displays an enhanced susceptibility to develop neuroendocrine-like phenotypes upon treatment with NTS. More importantly, NTSR1 pathway inhibition prevented the development of NED and castration resistance in vivo. We propose a novel role of NTS in the development of CRPC with NED, and a possible strategy to prevent the onset of NED by targeting the NTS signaling pathway.

On the Neuromodulatory Pathways of the In Vivo Brain by Means of Transcranial Focused Ultrasound.

For last decade, low-intensity transcranial focused ultrasound (tFUS) has been rapidly developed for a myriad of successful applications in neuromodulation. tFUS possesses high spatial resolution, focality and depth penetration as a noninvasive neuromodulation tool. Despite the promise, confounding activation can be observed in rodents when stimulation parameters are not selected carefully. Here we summarize the existing classes of observations for ultrasound neuromodulation: ultrasound directly activates a localized area, or ultrasound indirectly activates auditory pathways, which further propagates to other cortical networks. We also present control in vivo animal studies, which suggest that underlying tFUS brain modulation is characterized by localized activation independent of auditory networks activations.

YAP1 regulates prostate cancer stem cell-like characteristics to promote castration resistant growth.

Castration resistant prostate cancer (CRPC) is a stage of relapse that arises after various forms of androgen ablation therapy (ADT) and causes significant morbidity and mortality. However, the mechanism underlying progression to CRPC remains poorly understood. Here, we report that YAP1, which is negatively regulated by AR, influences prostate cancer (PCa) cell self-renewal and CRPC development. Specifically, we found that AR directly regulates the methylation of YAP1 gene promoter via the formation of a complex with Polycomb group protein EZH2 and DNMT3a. In normal conditions, AR recruits EZH2 and DNMT3a to YAP1 promoter, thereby promoting DNA methylation and the repression of YAP1 gene transcription. Following ADT treatment or when AR activity is antagonized by Bicalutamide or Enzalutamide, YAP1 gene expression is switched on. In turn, YAP1 promotes SOX2 and Nanog expression and the de-differentiation of PCa cells to stem/progenitor-like cells (PCSC), which potentially contribute to disease recurrence. Finally, the knock down of YAP1 expression or the inhibition of YAP1 function by Verteporfin in TRAMP prostate cancer mice significantly suppresses tumor recurrence following castration. In conclusion, our data reveals that AR suppresses YAP1 gene expression through a novel epigenetic mechanism, which is critical for PCa cells self-renewal and the development of CRPC.