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In the setting of multifocal tumors (25%) at RP, the cribriform morphologies were restricted to index tumors. Of 32 patients with available pre-RT biopsy information, 16 had GG1 PCa, none had cribriform morphologies at baseline but 81% demonstrated cribriform morphologies at RP. Notable alterations detected in the sequenced tumors included defects in DNA damage response and repair (DDR) genes (70%) (TP53, BRCA2, PALB2, ATR, POLQ), PTEN loss (50%), loss of 8p (80%), and gain of MYC (70%). The median tumor mutational burden was 4.18 mutations/Mb with a range of 2.16 to 31.86. Our findings suggest that most radiorecurrent PCas are enriched in cribriform morphologies with potentially targetable genomic alterations. Understanding this phenotypic and genotypic diversity of radiorecurrent PCa is critically important to facilitate optimal patient management.Colorectal cancers (CRCs) often display histological features indicative of aberrant differentiation but the molecular underpinnings of this trait and whether it directly drives disease progression is unclear. Here, we identify co-ordinate epigenetic inactivation of two epithelial-specific transcription factors, EHF and CDX1, as a mechanism driving differentiation loss in CRCs. Re-expression of EHF and CDX1 in poorly-differentiated CRC cells induced extensive chromatin remodelling, transcriptional re-programming, and differentiation along the enterocytic lineage, leading to reduced growth and metastasis. Strikingly, EHF and CDX1 were also able to reprogramme non-colonic epithelial cells to express colonic differentiation markers. By contrast, inactivation of EHF and CDX1 in well-differentiated CRC cells triggered tumour de-differentiation. Mechanistically, we demonstrate that EHF physically interacts with CDX1 via its PNT domain, and that these transcription factors co-operatively drive transcription of the colonic differentiation marker, VIL1. Compound genetic deletion of Ehf and Cdx1 in the mouse colon disrupted normal colonic differentiation and significantly enhanced colorectal tumour progression. These findings thus reveal a novel mechanism driving epithelial de-differentiation and tumour progression in CRC.To study the noise spectrum characteristics of marine pump units induced by different excitation sources, a computational aeroacoustic (CAA) model of the internal and external field noise of a marine pump was established. The coupled acoustic-vibration method was used to obtain the spectrum characteristics of internal and external field noise. The accuracy and feasibility of the simulation method for noise prediction were confirmed through a noise test. Due to the different mediums in the internal and external fields of the marine pump, an external field acoustic model was established based on the automatically matched layer (AML) technology. The spectral characteristics of different excitation sources and the spatial distribution of the radiated sound field were analyzed, and the contribution of different sound source excitations to the internal and external sound field was revealed. The results show that the main frequency of the internal field noise generated by different excitations is at the blade passing frequency, and the internal field noise induced by the dipole acoustic excitations dominates at 180.6 dB. For the external field noise, the main frequency is still located at the blade passing frequency. The radiation noise induced by the fluid excitation (139.2 dB) is higher than that induced by the dipole excitations (surface dipole, 136.3 dB; rotating dipole, 137.3 dB).The potential of the electrospray deposition technique as new method to make nanosheet-based multilayer films is evaluated. Densely packed nanosheet-based films with thicknesses of 1-20 nm with rms roughnesses of 2.1-2.4 nm were fabricated on samples of 1 cm2 size with a growth rate of 0.5 nm/min. Electrosprayed Ti0.87O2 nanosheet films were successfully used as oriented growth templates for 40 nm perovskite SrRuO3 thin films grown by pulsed laser deposition. The electrospray method provides a fast and easy alternative to the more commonly used Langmuir-Blodgett (LB) deposition method for nanosheet films.In this work, a methodology is presented for the determination of the respiration rate of a person under test (PUT), the detection of movements, as well as the elimination of the spurious effects produced by the movements of the PUT. The methodology is based on Empirical Modal Decomposition (EMD) applied to the phase signal obtained by means of a quadrature Doppler radar operating in S band. The EMD allows to automatically eliminate the continuos component (CC) which is present in the phase signal since one of the main characteristics of the modes generated by the EMD is that its mean is equal to zero. On the other hand, the first mode of the EMD is used for the detection of movements while the sum of the second and third modes are used for the elimination of the CC drift caused by the DC drift and the high frequency components produced by the movements of the PUT. IM156 The proposed methodology was successfully tested in a PUT at rest and performing movements of the head, arm and combination of head, arm, and torso. The average respiration rate measured was 20.78 breaths / min with a standard deviation of 2.53 breaths/min.Elevated circulating levels of nutrient-derived trimethylamine N-oxide (TMAO) have been associated with the onset and progression of cardiovascular disease by promoting athero-thrombosis. However, in conditions like bariatric surgery (Roux-en-Y gastric bypass, RYGB), stable increases of plasma TMAO are associated with improved endothelial function and reduced cardiovascular morbidity and mortality, thus questioning whether a mechanistic relationship between TMAO and endothelial dysfunction exists. Herein, we translationally assessed the effects of acute TMAO exposure on endothelial dysfunction, thrombosis and stroke. After RYGB, fasting circulating levels of TMAO increased in patients and obese rats, in parallel with an improved gluco-lipid profile and higher circulating bile acids. The latter enhanced FXR-dependent signalling in rat livers, which may lead to higher TMAO synthesis post RYGB. In lean rats, acute TMAO injection (7 mg kg-1) 1.5-h before sacrifice and ex-vivo 30-min incubation of thoracic aortas with 10-6 M TMAO did not impair vasodilation in response to acetylcholine (Ach), glucagon-like peptide 1, or insulin. Similarly, in lean WT mice (n = 5-6), TMAO injection prior to subjecting mice to ischemic stroke or arterial thrombosis did not increase its severity compared to vehicle treated mice. Endothelial nitric oxide synthase (eNOS) activity and intracellular stress-activated pathways remained unaltered in aorta of TMAO-injected rats, as assessed by Western Blot. Pre-incubation of human aortic endothelial cells with TMAO (10-6 M) did not alter NO release in response to Ach. Our results indicate that increased plasmatic TMAO in the near-physiological range seems to be a neutral bystander to vascular function as translationally seen in patients after bariatric surgery or in healthy lean rodent models and in endothelial cells exposed acutely to TMAO.Kawasaki Disease (KD) is systemic vasculitis involving medium-sized vessels in children. The aim of our study is to determine if fecal calprotectin (FC) could be useful in predicting the development or persistence of coronary artery lesions (CALs) in KD. We conducted a prospective monocentric study including all consecutive diagnoses of. Clinical, laboratory, echocardiographic data were recorded during the acute and subacute phase, including FC. Correlations among laboratory values, FC, clinical manifestations, IVIG-responsiveness and CALs development were investigated. We enrolled 26 children (76.9% boys; median age 34.5 months). The combination of FC > 250 microg/g and z-score > 2 during the acute phase was associated with the persistence of CALs (p = 0.022). A z-score > 2 alone during the acute phase was not related to CALs during the subacute stage (p > 0.05). A neutrophil percentage > 70% and WBC > 15,000/mmc during the acute phase significantly correlated with the presence of CALs during the subacute phase (p = 0.008). C-reactive protein (CRP) > 13 mg/dL at KD onset was significantly associated with the presence of CALs during the acute (p = 0.017) and subacute phase (p = 0.001). The combination of FC > 250 microg/g and a z-score > 2 during the acute phase of KD may be used as a predictor of CALs persistence. It can be useful especially in children with an initial CRP  less then  13 mg/dl.Metallic zinc (Zn) anode has been received a great promise for aqueous rechargeable zinc-ion batteries (ZIBs) due to its intrinsic safety, low cost, and high volumetric capacity. However, the dendrite formation regarding the surface corrosion is the critical problems to achieve the high performance and the long lifespans of ZIBs. Here, we purpose the facile cyclic voltammetry deposition of polypyrrole/reduced graphene oxide (PPy/rGO) composites coated onto Zn 3D surface as Zn anode for ZIBs. As results, the deposited PPy/rGO layer demonstrates the homogeneous distribution covering onto Zn surface, effectively suppressing the formation of dendrite. Additionally, a symmetric cell of the PPy/rGO coated Zn remarkably enhances an electrochemical cycling with a low voltage hysteresis for zinc plating/stripping, which is superior to the pristine Zn cell. In addition, the deposited layer of PPy/rGO on Zn effectively improves the reactivity of electrochemically active surface area and the intrinsic electronic configurations, participating in extraction/intercalation of Zn2+ ions and leading to enhance ZIBs performance. The coin cell battery of Zn-PPy/rGO//MnO2 can deliver a high initial discharge capacity of 325 mAh/g at 0.5A/g with a good cycling stability up to 50% capacity retention after 300 cycles. Thus, these achieved results of Zn-PPy/rGO//MnO2 battery with dendrite-free feature effectively enhance the life-performance of ZIBs and open the way of the designed coating composite materials to suppress dendrite issues.Cancer immunoediting drives the adaptation of tumor cells to host immune surveillance. Previously, we have demonstrated that immunoediting driven by cytotoxic T lymphocytes (CTLs) enriches NANOG+ tumor cells with immune-refractory properties. Here, we found that CTL-mediated immune pressure triggered cross-resistance of tumor cells to the complement system, a part of the innate immune system. In this process, NANOG upregulated the membrane-bound complement regulatory protein (mCRP) CD59 through promoter occupancy, thereby contributing to the resistance of tumor cells against complement-dependent cytotoxicity (CDC). Notably, targeting of NANOG sensitized the immune-refractory tumor cells to trastuzumab-mediated CDC. Collectively, our results revealed a possible mechanism through which selection imposed by T-cell based immunotherapy triggered complement-resistant phenotypes in the tumor microenvironment (TME), by establishing a firm molecular link between NANOG and CD59 in immune-edited tumor cells. We believe these results hold important implications for the clinical application of CDC-mediated therapeutic antibody.