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01). Reclassified patients had significantly higher sST2 at baseline and higher NT-proBNP values at baseline and 6 months follow-up compared to non-reclassified patients. Acute kidney injury was experienced more frequently after TAVR by reclassified patients, but no significant mortality difference occurred during 2 years of follow-up. CONCLUSION The hybrid AVAi reclassifies a significant portion of low-gradient severe AS patients into moderate AS. Reclassified patients showed increased fibrosis and heart failure markers at baseline compared to non-reclassified patients. But reclassification had no significant impact on mortality up to 2 years after TAVR. Routine assessment of hybrid AVAi seems not to improve further risk stratification of TAVR patients. © 2020 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals, Inc.Successful combinations of visible light photocatalysis with transition metal catalysis have recently enabled the development of hitherto unknown chemical transformations. Such dual catalytic mechanisms by merging metal-free photocatalysts and earth-abundant metal catalysts are still in their infancy. Here, we report a photo-organo-iron-catalyzed cyclotrimerization of alkynes that involves photo-redox-activation of a ligand-free Fe catalyst. The reaction operates under very mild conditions (Vis light, room temp., 1 h) with 1-2 mol% loading of the three catalysts (dye, amine, FeCl 2 ). © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Developing a novel tool capable of real-time monitoring and simultaneous quantification of multiple neurochemicals, together with recording of electrical signals in a live brain has long been a prominent challenge. Here, we created an electrochemophysiological microarray (ECPM) for real-time mapping and simultaneous quantification of chemical signals for multiple ions in the deep brain of freely moving rat, in which selective and accurate microelectrode arrays were developed for direct determination of K + , Ca 2+ , Na + and pH using open-circuit potentiometry. Specific recognition ionophores were synthesized and optimized for determination of K + , Ca 2+ , Na + and pH. An inner-reference electrode was also developed to provide a built-in correction for avoiding interferences in the complicated brain. The developed microarrays demonstrating high accuracy and selectivity were successfully applied in real-time monitoring and simultaneous quantification of multi-ions in a live brain. The extra current-free potentiometry allowed mapping and biosensing of chemical signals, together with recording of electrical signals in the whole brain without cross-talk, for the first time. Furthermore, the present ECPM having high anti-fouling property and long-term stability provided a platform for real-time tracking the dynamic changes of multiple ions in the deep brain of freely moving rat under seizure status. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Multidrug-resistant bacteria represent one of the biggest challenges facing modern medicine. The development of resistances results in an exhaustion of the pool of antibacterial substances, mostly natural products that have been perfected by evolution to a dedicated target. The increasing prevalence of glycopeptide resistance compromises the efficacy of vancomycin, for a long time considered as the last resort for the treatment of resistant bacteria. In order to reestablish its activity, polycationic peptides were conjugated to vancomycin. By site-specific conjugation, derivatives that bear the peptide moiety at four different sites of the antibiotic were synthesized. The most potent compounds exhibited an approximately 1,000-fold increased antimicrobial activity and were able to overcome the most important types of vancomycin resistance. Additional blocking experiments using D-Ala-D-Ala revealed the prevalence of a mode of action beyond cell wall inhibition. As further highlight, the antimicrobial potential of the lead candidate FU002 for bacterial infection treatments could be demonstrated in an in vivo efficacy study. Furthermore, molecular imaging and biodistribution studies revealed that conjugation engenders superior pharmacokinetics. These findings show that medicinal chemistry enables the preservation of seasoned compounds, a fundamentally new approach which avoids the interminable work of de novo antibiotic development. https://www.selleckchem.com/Proteasome.html © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.BACKGROUND Germline DNA damage repair gene mutations (gDDRm) have been found in approximately 12% of patients with metastatic prostate cancer (mPCa). Previous studies of the clinical impact of gDDRm have mainly been in the setting of metastatic castration-resistant prostate cancer (mCRPC). This study aimed to determine the prognostic value of gDDRm in de novo metastatic and castration-sensitive prostate cancer (mCSPC). MATERIALS AND METHODS We retrospectively collected the records of 139 consecutive men with de novo mCSPC who initially received systemic therapies following guidelines. This included 128 patients who underwent genetic testing at our center and 11 patients referred to our center after being identified as gDDRm carriers. Time to mCRPC was collected. Kaplan-Meier and log-rank analysis were used to analyze the association between gDDRm and clinical outcomes. Survival outcomes were adjusted using multivariable Cox regression models. RESULTS Of the 139 patients with de novo mCSPC, 28 gDDRm carriers w-ribose) polymerase inhibitors, and our results call for more frontline targeted therapy trials in gDDRm carriers to prolong the progression time. IMPLICATIONS FOR PRACTICE Results of this study suggested that positive germline DNA damage repair gene mutation (gDDRm) status predicted earlier progression to castration resistance in patients with de novo metastatic and castration-sensitive prostate cancer (mCSPC). These findings indicated the importance of intense therapy for some subgroups of mCSPC, especially for mCSPC harboring gDDRm with low-volume disease. Moreover, gDDRm was a good therapeutic target for poly (ADP-ribose) polymerase inhibitors, and these findings call for more molecular marker driven trials moving to the mTNPC setting. © AlphaMed Press 2020.