Bi-steric mTORC1 inhibitors induce apoptotic cell death in tumor models with hyperactivated mTORC1.

The PI3K/AKT/mTOR pathway is commonly dysregulated in cancer. Rapalogs exhibit modest clinical benefit, likely owing to their lack of effects on 4EBP1. We hypothesized that bi-steric mTORC1-selective inhibitors would have greater potential for clinical benefit than rapalogs in tumors with mTORC1 dysfunction.

Biomimetic Carbon Sequestration and Cyanate Detoxification Using Heat-Purified Carbonic Anhydrase from .

The reaction condition for purifying carbonic anhydrase from (SspCA) by direct heating without prior cell lysis was optimized; heating at 70 °C for 5 min resulted in the highest total activity of 23,460 WAU (Wilbur-Anderson unit) from a 50 mL culture. Heat-purified SspCA was examined for its capability to increase the rate of the mineralization of CO; compared with an uncatalyzed control, the onset time of CaCO formation was shortened by up to 71%. Cyanase can be used to degrade toxic cyanate; however, one of the limitations of this biomimetic process is that the reaction needs HCO as a substrate.

A bi-steric mTORC1-selective inhibitor overcomes drug resistance in breast cancer.

Activation of the PI3K-mTOR pathway is central to breast cancer pathogenesis including resistance to many targeted therapies. The mTOR kinase forms two distinct complexes, mTORC1 and mTORC2, and understanding which is required for the survival of malignant cells has been limited by tools to selectively and completely impair either subcomplex. To address this, we used RMC-6272, a bi-steric molecule with a rapamycin-like moiety linked to an mTOR active-site inhibitor that displays >25-fold selectivity for mTORC1 over mTORC2 substrates.

Defining cellular population dynamics at single-cell resolution during prostate cancer progression.

Advanced prostate malignancies are a leading cause of cancer-related deaths in men, in large part due to our incomplete understanding of cellular drivers of disease progression. We investigate prostate cancer cell dynamics at single-cell resolution from disease onset to the development of androgen independence in an in vivo murine model. We observe an expansion of a castration-resistant intermediate luminal cell type that correlates with treatment resistance and poor prognosis in human patients.

Bimodal Multiplexed Detection of Tumor Markers in Non-Small Cell Lung Cancer with Polymer Dot-Based Immunoassay.

Semiconducting polymer nanoparticles (Pdots) have been demonstrated to be a promising class of probes for use in fluorometric immunochromatographic test strips (ICTS). The advantages of Pdots in ICTSs include ultrahigh brightness, minimal nonspecific adsorption, and multicolor availability, which together contribute to the high sensitivity, good specificity, and multiplexing ability. These unique properties can therefore circumvent several significant challenges of commercial ICTSs, including insufficient specificity/sensitivity and difficulty in quantitative and multiplexed detection.

Entrapment of the Fastest Known Carbonic Anhydrase with Biomimetic Silica and Its Application for CO Sequestration.

Capturing and storing CO is of prime importance. The rate of CO sequestration is often limited by the hydration of CO, which can be greatly accelerated by using carbonic anhydrase (CA, EC 4.2.

Polymethine-Based Semiconducting Polymer Dots with Narrow-Band Emission and Absorption/Emission Maxima at NIR-II for Bioimaging.

Deep-penetration fluorescence imaging in the second near-infrared (NIR-II) window heralds a new era of clinical surgery, in which high-resolution vascular/lymphatic anatomy and detailed cancerous tissues can be visualized in real time. Described here is a series of polymethine-based semiconducting polymers with intrinsic emission maxima in the NIR-IIa (1300-1400 nm) window and absorption maxima ranging from 1082 to 1290 nm. These polymers were prepared as semiconducting polymer dots (Pdots) in aqueous solutions with fluorescence quantum yields of 0.

Surfactant-assisted in situ transesterification of wet Rhodotorula glutinis biomass.

In situ transesterification of oleaginous microbes with short chain alcohol has been developed as a renewable process for the production of biodiesel. Dry biomass is often a requisite for the process to avoid the adverse effect of water on the productivity. As a consequence, large amount of energy consumption is required for prior biomass drying.

Cyanine-Based Polymer Dots with Long-Wavelength Excitation and Near-Infrared Fluorescence beyond 900 nm for Biological Imaging.

Bioimaging in the near-infrared window is of great importance to study the dynamic processes with deep penetration, high spatiotemporal resolution, and minimal tissue absorption, scattering, and autofluorescence. In spite of the huge progress on the synthesis of small organic fluorophores and inorganic nanomaterials with emissions beyond 900 nm, it remains a tough challenge to synthesize semiconducting polymers with fluorescence over this region. Here, we synthesized a series of heptamethine cyanine-based polymers with both absorption and emission in the near-infrared region.

Revealing Metabolic Liabilities of Ralaniten To Enhance Novel Androgen Receptor Targeted Therapies.

Inhibition of the androgen receptor (AR) is the mainstay treatment for advanced prostate cancer. Ralaniten (formally EPI-002) prevents AR transcriptional activity by binding to its N-terminal domain (NTD) which is essential for transcriptional activity. Ralaniten acetate (EPI-506) the triacetate pro-drug of ralaniten, remains the only AR-NTD inhibitor to have entered clinical trials (NCT02606123).

FRET-Created Traffic Light Immunoassay Based on Polymer Dots for PSA Detection.

There have been enormous efforts for developing the next generations of fluorometric lateral flow immunochromatographic strip (ICTS) owing to the great advances in fluorescent materials in these years. Here we developed one type of fluorometric ICTS based on ultrabright semiconducting polymer dots (Pdots) in which the traffic light-like signals were created by energy transfer depending on the target concentration. This platform was successfully applied for qualitatively rapid screening and quantitatively precise analysis of prostate-specific antigen (PSA) in 10 min from merely one drop of the whole blood sample.

Androgen Receptor Pathway-Independent Prostate Cancer Is Sustained through FGF Signaling.

Androgen receptor (AR) signaling is a distinctive feature of prostate carcinoma (PC) and represents the major therapeutic target for treating metastatic prostate cancer (mPC). Though highly effective, AR antagonism can produce tumors that bypass a functional requirement for AR, often through neuroendocrine (NE) transdifferentiation. Through the molecular assessment of mPCs over two decades, we find a phenotypic shift has occurred in mPC with the emergence of an AR-null NE-null phenotype.

Differential effects of DEAE negative mode chromatography and gel-filtration chromatography on the charge status of Helicobacter pylori neutrophil-activating protein.

Helicobacter pylori neutrophil-activating protein (HP-NAP) is involved in H. pylori-associated gastric inflammation. HP-NAP is also a vaccine candidate, a possible drug target, and a potential diagnostic marker for H.

Sintokamide A Is a Novel Antagonist of Androgen Receptor That Uniquely Binds Activation Function-1 in Its Amino-terminal Domain.

Androgen receptor (AR) is a validated drug target for all stages of prostate cancer including metastatic castration-resistant prostate cancer (CRPC). All current hormone therapies for CRPC target the C-terminal ligand-binding domain of AR and ultimately all fail with resumed AR transcriptional activity. Within the AR N-terminal domain (NTD) is activation function-1 (AF-1) that is essential for AR transcriptional activity.

One-step Negative Chromatographic Purification of Helicobacter pylori Neutrophil-activating Protein Overexpressed in Escherichia coli in Batch Mode.

Helicobacter pylori neutrophil-activating protein (HP-NAP) is a major virulence factor of Helicobacter pylori (H. pylori). It plays a critical role in H.

Targeting Androgen Receptor Activation Function-1 with EPI to Overcome Resistance Mechanisms in Castration-Resistant Prostate Cancer.

Purpose: Persistent androgen receptor (AR) transcriptional activity is clinically evident in castration-resistant prostate cancer (CRPC). Therefore, AR remains as a viable therapeutic target for CRPC. All current hormonal therapies target the C-terminus ligand-binding domain (LBD) of AR.

Mineralization Effect of Hyaluronan on Dental Pulp Cells via CD44.

Introduction: CD44 is a cell-surface glycoprotein involved in various cellular functions. Recent studies have suggested that CD44 is involved in early mineralization of odontoblasts. Hyaluronic acid (HA) is the principal ligand for receptor CD44.

Protective effects of (-)-epigallocatechin-3-gallate against acetaminophen-induced liver injury in rats).

(-)-Epigallocatechin-3-gallate (EGCG) is the most abundant catechin with various biological activities found in tea. In this study, the effects of EGCG on the metabolism and toxicity of acetaminophen in rat liver were investigated. Male Sprague-Dawley rats were fed a controlled diet without or with EGCG (0.

High yield purification of Helicobacter pylori neutrophil-activating protein overexpressed in Escherichia coli.

Background: Helicobacter pylori neutrophil-activating protein (HP-NAP) is involved in H. pylori-induced gastric inflammation. Due to its immunogenic and immunomodulatory properties, HP-NAP has been used for developing vaccines against H.

Characterization of niphatenones that inhibit androgen receptor N-terminal domain.

Androgen ablation therapy causes a temporary reduction in tumor burden in patients with advanced prostate cancer. Unfortunately the malignancy will return to form lethal castration-recurrent prostate cancer (CRPC). The androgen receptor (AR) remains transcriptionally active in CRPC in spite of castrate levels of androgens in the blood.

The written language performance of children with Attention Deficit Hyperactivity Disorder in Taiwan.

Poor writing is common in children with Attention Deficit Hyperactivity Disorder (ADHD). However, the writing performance of children with ADHD has been rarely formally explored in Taiwan, so the purpose of this study was to investigate writing features of children with ADHD in Taiwan. There were 25 children with ADHD and 25 normal children involved in a standardization writing assessment - Written Language Test for Children, to assess their performance at the dictation, sentence combination, adding/deducting redical, cloze and sentence making subtests.

Optimized production of biodiesel from waste cooking oil by lipase immobilized on magnetic nanoparticles.

Biodiesel, a non-toxic and biodegradable fuel, has recently become a major source of renewable alternative fuels. Utilization of lipase as a biocatalyst to produce biodiesel has advantages over common alkaline catalysts such as mild reaction conditions, easy product separation, and use of waste cooking oil as raw material. In this study, Pseudomonas cepacia lipase immobilized onto magnetic nanoparticles (MNP) was used for biodiesel production from waste cooking oil.

An androgen receptor N-terminal domain antagonist for treating prostate cancer.

Hormone therapies for advanced prostate cancer target the androgen receptor (AR) ligand-binding domain (LBD), but these ultimately fail and the disease progresses to lethal castration-resistant prostate cancer (CRPC). The mechanisms that drive CRPC are incompletely understood, but may involve constitutively active AR splice variants that lack the LBD. The AR N-terminal domain (NTD) is essential for AR activity, but targeting this domain with small-molecule inhibitors is complicated by its intrinsic disorder.

One-step chromatographic purification of Helicobacter pylori neutrophil-activating protein expressed in Bacillus subtilis.

Helicobacter pylori neutrophil-activating protein (HP-NAP), a major virulence factor of Helicobacter pylori (H. pylori), is capable of activating human neutrophils to produce reactive oxygen species (ROS) and secrete inammatory mediators. HP-NAP is a vaccine candidate, a possible drug target, and a potential in vitro diagnostic marker for H.