Thioamide-based fluorescent sensors for dipeptidyl peptidase 4.

Dipeptidyl peptidase 4 (DPP-4) is a promising biomarker for cancer and metabolic diseases. We demonstrate the design of novel fluorescent DPP-4 probes based on the protease's native substrates using a thioamide as a quencher for measuring kinetics, inhibition with sitagliptin, and DPP-4 activity in saliva samples.

Consistent predictive ability of prostate-specific antigen density prediction model for clinically significant prostate cancer across age strata.

Background: Prebiopsy prostate-specific antigen density (PSAD) is a well-known predictor of clinically significant prostate cancer (csPCa). Since prostate-specific antigen (PSA) and prostate volume (PV) increase normally with aging, PSAD thresholds may vary. The purpose of the study was to determine if PSAD was predictive of csPCa in different age strata.

Optimising postoperative care: Same-day discharge after transurethral resection of the prostate.

Introduction: This study aims to assess the feasibility and safety of same-day discharge after transurethral resection of the prostate.

Materials And Methods: Five years of records were retrospectively analysed. Length of stay categorised patients into Groups 1 (same-day discharge) and 2 (standard-length discharge).

Structure-Based Engineering of a Sesquiterpene Cyclase to Generate an Alcohol Product: Conversion of -Isozizaene Synthase into α-Bisabolol Synthase.

The sesquiterpene cyclase -isozizaene synthase (EIZS) from catalyzes the metal-dependent conversion of farnesyl diphosphate (FPP) into the complex tricyclic product -isozizaene. This remarkable transformation is governed by an active site contour that serves as a template for catalysis, directing the conformations of multiple carbocation intermediates leading to the final product. Mutagenesis of residues defining the active site contour remolds its three-dimensional shape and reprograms the cyclization cascade to generate alternative cyclization products.

Reprogramming the Cyclization Cascade of -Isozizaene Synthase to Generate Alternative Terpene Products.

The class I sesquiterpene cyclase -isozizaene synthase from (EIZS) catalyzes the transformation of linear farnesyl diphosphate (FPP) into the tricyclic hydrocarbon -isozizaene in the biosynthesis of albaflavenone antibiotics. The active site cavity of EIZS is largely framed by four aromatic residues - F95, F96, F198, and W203 - that form a product-shaped contour, serving as a template to chaperone conformations of the flexible substrate and multiple carbocation intermediates leading to -isozizaene. Remolding the active site contour by mutagenesis can redirect the cyclization cascade away from -isozizaene biosynthesis to generate alternative sesquiterpene products.

Structural Basis of Substrate Promiscuity and Catalysis by the Reverse Prenyltransferase -Dimethylallyl-l-tryptophan Synthase from .

The regiospecific prenylation of an aromatic amino acid catalyzed by a dimethylallyl-l-tryptophan synthase (DMATS) is a key step in the biosynthesis of many fungal and bacterial natural products. DMATS enzymes share a common "ABBA" fold with divergent active site contours that direct alternative C-C, C-N, and C-O bond-forming trajectories. DMATS1 from catalyzes the reverse N-prenylation of l-Trp by generating an allylic carbocation from dimethylallyl diphosphate (DMAPP) that then alkylates the indole nitrogen of l-Trp.

Engineering the Prenyltransferase Domain of a Bifunctional Assembly-Line Terpene Synthase.

Copalyl diphosphate (CPP) synthase from (PvCPS) is a bifunctional diterpene synthase with both prenyltransferase and class II cyclase activities. The prenyltransferase α domain catalyzes the condensation of C dimethylallyl diphosphate with three successively added C isopentenyl diphosphates (IPPs) to form C geranylgeranyl diphosphate (GGPP), which then undergoes a class II cyclization reaction at the βγ domain interface to generate CPP. The prenyltransferase α domain mediates oligomerization to form a 648-kD (αβγ) hexamer.

The Invisible Danger of Transferring Toxins with Bunker Gear: A Theory-Based Intervention to Increase Postfire Decontamination to Reduce Cancer Risk in Firefighters.

Studies show significant association between cancer risk and being a firefighter. After exposure to even routine firefighting, firefighters' bunker gear often contains carcinogens that may be absorbed through contact or inhaled through off-gassing, thereby increasing cancer risk. Awareness of increased cancer risk has given rise to policies and practices focused on gear cleaning and decontamination processes to decrease risk; yet, these efforts are in their infancy and tend to be somewhat piecemeal in nature.

Psychiatric Diagnoses and Other Factors Associated with Emergency Department Return within 30 Days of Ureteroscopy.

Purpose: Emergency department visits after ureteroscopy are costly and inconvenient. To better understand those at risk we aimed to identify patient demographic, medical and surgical factors associated with 30-day emergency department presentation following ureteroscopy for urolithiasis with particular attention to those with a history of a psychiatric diagnosis.

Materials And Methods: We retrospectively reviewed 1,576 cases (1,395 adults) who underwent stone related ureteroscopy during 3 years at a total of 2 hospitals.

Increasing Cardiomyocyte Atrogin-1 Reduces Aging-Associated Fibrosis and Regulates Remodeling in Vivo.

The muscle-specific ubiquitin ligase atrogin-1 (MAFbx) has been identified as a critical regulator of pathologic and physiological cardiac hypertrophy; it regulates these processes by ubiquitinating transcription factors [nuclear factor of activated T-cells and forkhead box O (FoxO) 1/3]. However, the role of atrogin-1 in regulating transcription factors in aging has not previously been described. Atrogin-1 cardiomyocyte-specific transgenic (Tg) adult mice (α-major histocompatibility complex promoter driven) have normal cardiac function and size.

Nurse-Initiated Telephone Follow Up after Ureteroscopic Stone Surgery.

This article presents findings of a quality improvement (QI) project using the DMAIC (define, measure, analyze, improve, and control) model designed to decrease the rate of emergency department (ED) visits and nurse advice line calls after ureteroscopic stone surgery. Results indicated that nurse-initiated follow- up phone calls can decrease ED visits.

Spatially resolved multicolor CsPbX nanowire heterojunctions via anion exchange.

Halide perovskites are promising semiconductor materials for solution-processed optoelectronic devices. Their strong ionic bonding nature results in highly dynamic crystal lattices, inherently allowing rapid ion exchange at the solid-vapor and solid-liquid interface. Here, we show that the anion-exchange chemistry can be precisely controlled in single-crystalline halide perovskite nanomaterials when combined with nanofabrication techniques.

MYC activation cooperates with Vhl and Ink4a/Arf loss to induce clear cell renal cell carcinoma.

Renal carcinoma is a common and aggressive malignancy whose histopathogenesis is incompletely understood and that is largely resistant to cytotoxic chemotherapy. We present two mouse models of kidney cancer that recapitulate the genomic alterations found in human papillary (pRCC) and clear cell RCC (ccRCC), the most common RCC subtypes. MYC activation results in highly penetrant pRCC tumours (MYC), while MYC activation, when combined with Vhl and Cdkn2a (Ink4a/Arf) deletion (VIM), produce kidney tumours that approximate human ccRCC.

Cardiomyocyte-Specific Human Bcl2-Associated Anthanogene 3 P209L Expression Induces Mitochondrial Fragmentation, Bcl2-Associated Anthanogene 3 Haploinsufficiency, and Activates p38 Signaling.

The Bcl2-associated anthanogene (BAG) 3 protein is a member of the BAG family of cochaperones, which supports multiple critical cellular processes, including critical structural roles supporting desmin and interactions with heat shock proteins and ubiquitin ligases intimately involved in protein quality control. The missense mutation P209L in exon 3 results in a primarily cardiac phenotype leading to skeletal muscle and cardiac complications. At least 10 other Bag3 mutations have been reported, nine resulting in a dilated cardiomyopathy for which no specific therapy is available.

Synthesis of Composition Tunable and Highly Luminescent Cesium Lead Halide Nanowires through Anion-Exchange Reactions.

Here, we demonstrate the successful synthesis of brightly emitting colloidal cesium lead halide (CsPbX3, X = Cl, Br, I) nanowires (NWs) with uniform diameters and tunable compositions. By using highly monodisperse CsPbBr3 NWs as templates, the NW composition can be independently controlled through anion-exchange reactions. CsPbX3 alloy NWs with a wide range of alloy compositions can be achieved with well-preserved morphology and crystal structure.

Growth and Photoelectrochemical Energy Conversion of Wurtzite Indium Phosphide Nanowire Arrays.

Photoelectrochemical (PEC) water splitting into hydrogen and oxygen is a promising strategy to absorb solar energy and directly convert it into a dense storage medium in the form of chemical bonds. The continual development and improvement of individual components of PEC systems is critical toward increasing the solar to fuel efficiency of prototype devices. Within this context, we describe a study on the growth of wurtzite indium phosphide (InP) nanowire (NW) arrays on silicon substrates and their subsequent implementation as light-absorbing photocathodes in PEC cells.

Lasing in robust cesium lead halide perovskite nanowires.

The rapidly growing field of nanoscale lasers can be advanced through the discovery of new, tunable light sources. The emission wavelength tunability demonstrated in perovskite materials is an attractive property for nanoscale lasers. Whereas organic-inorganic lead halide perovskite materials are known for their instability, cesium lead halides offer a robust alternative without sacrificing emission tunability or ease of synthesis.

Solution-Processed Copper/Reduced-Graphene-Oxide Core/Shell Nanowire Transparent Conductors.

Copper nanowire (Cu NW) based transparent conductors are promising candidates to replace ITO (indium-tin-oxide) owing to the high electrical conductivity and low-cost of copper. However, the relatively low performance and poor stability of Cu NWs under ambient conditions limit the practical application of these devices. Here, we report a solution-based approach to wrap graphene oxide (GO) nanosheets on the surface of ultrathin copper nanowires.

Highly Luminescent Colloidal Nanoplates of Perovskite Cesium Lead Halide and Their Oriented Assemblies.

Anisotropic colloidal quasi-two-dimensional nanoplates (NPLs) hold great promise as functional materials due to their combination of low dimensional optoelectronic properties and versatility through colloidal synthesis. Recently, lead-halide perovskites have emerged as important optoelectronic materials with excellent efficiencies in photovoltaic and light-emitting applications. Here we report the synthesis of quantum confined all inorganic cesium lead halide nanoplates in the perovskite crystal structure that are also highly luminescent (PLQY 84%).

Atomically thin two-dimensional organic-inorganic hybrid perovskites.

Organic-inorganic hybrid perovskites, which have proved to be promising semiconductor materials for photovoltaic applications, have been made into atomically thin two-dimensional (2D) sheets. We report the solution-phase growth of single- and few-unit-cell-thick single-crystalline 2D hybrid perovskites of (C4H9NH3)2PbBr4 with well-defined square shape and large size. In contrast to other 2D materials, the hybrid perovskite sheets exhibit an unusual structural relaxation, and this structural change leads to a band gap shift as compared to the bulk crystal.

Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) remains a lethal disease with a 5-year survival rate of 4%. A key hallmark of PDAC is extensive stromal involvement, which makes capturing precise tumor-specific molecular information difficult. Here we have overcome this problem by applying blind source separation to a diverse collection of PDAC gene expression microarray data, including data from primary tumor, metastatic and normal samples.

Growth and Anion Exchange Conversion of CH3NH3PbX3 Nanorod Arrays for Light-Emitting Diodes.

The nanowire and nanorod morphology offers great advantages for application in a range of optoelectronic devices, but these high-quality nanorod arrays are typically based on high temperature growth techniques. Here, we demonstrate the successful room temperature growth of a hybrid perovskite (CH3NH3PbBr3) nanorod array, and we also introduce a new low temperature anion exchange technique to convert the CH3NH3PbBr3 nanorod array into a CH3NH3PbI3 nanorod array while preserving morphology. We demonstrate the application of both these hybrid perovskite nanorod arrays for LEDs.

Solution-Phase Synthesis of Cesium Lead Halide Perovskite Nanowires.

Halide perovskites have attracted much attention over the past 5 years as a promising class of materials for optoelectronic applications. However, compared to hybrid organic-inorganic perovskites, the study of their pure inorganic counterparts, like cesium lead halides (CsPbX3), lags far behind. Here, a catalyst-free, solution-phase synthesis of CsPbX3 nanowires (NWs) is reported.

AAV-mediated gene delivery in a feline model of Sandhoff disease corrects lysosomal storage in the central nervous system.

Sandhoff disease (SD) is an autosomal recessive neurodegenerative disease caused by a mutation in the gene for the β-subunit of β-N-acetylhexosaminidase (Hex), resulting in the inability to catabolize ganglioside GM2 within the lysosomes. SD presents with an accumulation of GM2 and its asialo derivative GA2, primarily in the central nervous system. Myelin-enriched glycolipids, cerebrosides and sulfatides, are also decreased in SD corresponding with dysmyelination.