RILP Induces Cholesterol Accumulation in Lysosomes by Inhibiting Endoplasmic Reticulum-Endolysosome Interactions.

Endoplasmic reticulum (ER)-endolysosome interactions regulate cholesterol exchange between the ER and the endolysosome. ER-endolysosome membrane contact sites mediate the ER-endolysosome interaction. VAP-ORP1L (vesicle-associated membrane protein-associated protein- OSBP-related protein 1L) interaction forms the major contact site between the ER and the lysosome, which is regulated by Rab7.

Acoustic Ejection Mass Spectrometry for High-Throughput Analysis.

We describe a mass spectrometry (MS) analytical platform resulting from the novel integration of acoustic droplet ejection (ADE) technology, an open-port interface (OPI), and electrospray ionization (ESI)-MS that creates a transformative system enabling high-speed sampling and label-free analysis. The ADE technology delivers nanoliter droplets in a touchless manner with high speed, precision, and accuracy. Subsequent sample dilution within the OPI, in concert with the capabilities of modern ESI-MS, eliminates the laborious sample preparation and method development required in current approaches.

A deep learning-based ensemble method for helmet-wearing detection.

Recently, object detection methods have developed rapidly and have been widely used in many areas. In many scenarios, helmet wearing detection is very useful, because people are required to wear helmets to protect their safety when they work in construction sites or cycle in the streets. However, for the problem of helmet wearing detection in complex scenes such as construction sites and workshops, the detection accuracy of current approaches still needs to be improved.

Ultra-High-Throughput Acoustic Droplet Ejection-Open Port Interface-Mass Spectrometry for Parallel Medicinal Chemistry.

High-throughput experimentation (HTE) has emerged as an important tool in drug discovery, providing a platform for preparing large compound libraries and enabling swift reaction screening over wide-ranging conditions. Recent advances in automated high-density, material-sparing HTE have necessitated the development of rapid analytics with sensitivity and resolution sufficient to identify products and/or assess reaction performance in a timely and data-rich manner. Combination of an ultrathroughput (UT) reader platform with Acoustic Droplet Ejection-Open Port Interface-Mass Spectrometry (ADE-OPI-MS) provides the requisite speed and sensitivity.

11-Hydroxysteroid Dehydrogenase 1 Human Tissue Distribution, Selective Inhibitor, and Role in Doxorubicin Metabolism.

11-Hydroxysteroid dehydrogenase 1 (11-HSD1) is distributed mainly in the human liver, with no detectable levels in the intestine or kidney, based on a newly developed proteomic approach. 11-HSD1 is mostly membrane-bound and retained in the liver microsomal fraction. Interindividual variability of 11-HSD1 is relatively low, with about a 3-fold difference.

Novel Method to Predict In Vivo Liver-to-Plasma K for OATP Substrates Using Suspension Hepatocytes.

The ability to predict human liver-to-plasma unbound partition coefficient (K) is of great importance to estimate unbound liver concentration, develop PK/PD relationships, predict efficacy and toxicity in the liver, and model the drug-drug interaction potential for drugs that are asymmetrically distributed into the liver. A novel in vitro method has been developed to predict in vivo K with good accuracy using cryopreserved suspension hepatocytes in InVitroGRO HI media with 4% BSA. Validation was performed using six OATP substrates with rat in vivo K data from i.

Human Tissue Distribution of Carbonyl Reductase 1 Using Proteomic Approach With Liquid Chromatography-Tandem Mass Spectrometry.

Human tissue distribution of carbonyl reductase 1 (CBR1) is quite controversial in the literature. To understand the differences, CBR1 protein abundance in human intestine, liver, and kidney has been determined using a proteomic approach with liquid chromatography-tandem mass spectrometry. The results show that CBR1 distribution in the 3 tissues is relatively similar, within 2- to 3-folds of each other.

Development of a sensitive and fast UHPLC-MS/MS method for determination of clopidogrel, clopidogrel acid and clopidogrel active metabolite H4 in human plasma.

Background: Quantitation of CAM H4 in biological matrix has been a challenge due to low concentrations, instability and the existence of four CAM diastereomers. Historically, either inactive clopidogrel acid or CAM diastereomers without separation were measured for exposure and PK parameters.

Results: This study presents a sensitive and fast UHPLC-MS/MS method for simultaneous quantitation of clopidogrel, clopidogrel acid and active metabolite H4 in human plasma.

Development and validation of a HILIC-MS/MS method for quantification of decitabine in human plasma by using lithium adduct detection.

A highly sensitive, selective, and rugged quantification method was developed and validated for decitabine (5-aza-2'-deoxycytidine) in human plasma treated with 100μg/mL of tetrahydrouridine (THU). Chromatographic separation was accomplished using hydrophilic interaction liquid chromatography (HILIC) and detection used electrospray ionization (ESI) tandem mass spectrometry (MS/MS) by monitoring lithiated adducts of the analytes as precursor ions. The method involves simple acetonitrile precipitation steps (in an ice bath) followed by injection of the supernatant onto a Thermo Betasil Silica-100, 100×3.

Ozone treatment and the depletion of detectable pharmaceuticals and atrazine herbicide in drinking water sourced from the upper Detroit River, Ontario, Canada.

The depletion and degradation of pharmacologically active compounds (PhACs) and pesticides as a function of ozonation in drinking water treatment processes is not well studied. The A.H.

Triclosan in waste and surface waters from the upper Detroit River by liquid chromatography-electrospray-tandem quadrupole mass spectrometry.

Triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol) is an antimicroibial disinfectant agent used in a wide array of consumer products. An analytical method based on solid-phase extraction (SPE) followed by reverse phase, liquid chromatography coupled with electrospray ionization (negative)-tandem quadrupole mass spectrometry (LC-ESI(-)-MS/MS; in the multiple reaction monitoring (MRM) mode) was developed, optimized and validated for the determination of triclosan in wastewater/sewage treatment plant (WSTP) effluent and surface waters from the upper Detroit River (Canada). The mean recoveries (+/-%RSD) of triclosan and the internal standard 2'-HO-tribromodiphenyl ether (2'-HO-BDE-28) spiked to surface water and WSTP effluent samples ranged similarly from 104+/-8% and 91+/-10%, respectively, and method limits of quantification were in the low ppb/high ppt range.