Survey of Pharmaceutical Industry's Best Practices around In Vitro Transporter Assessment and Implications for Drug Development: Considerations from the International Consortium for Innovation and Quality for Pharmaceutical Development Transporter Working Group.

The International Consortium for Innovation and Quality in Pharmaceutical Development Transporter Working Group had a rare opportunity to analyze a crosspharma collation of in vitro data and assay methods for the evaluation of drug transporter substrate and inhibitor potential. Experiments were generally performed in accordance with regulatory guidelines. Discrepancies, such as not considering the impact of preincubation for inhibition and free or measured in vitro drug concentrations, may be due to the retrospective nature of the dataset and analysis.

Assessing the Feasibility of Biorefineries for a Sustainable Citrus Waste Management in Korea.

Citrus fruits are one of the most widely used fruits around the world and are used as raw fruits, but are also processed into products such as beverages, and large amounts of by-products and waste are generated in this process. Globally, disposal of citrus waste (CW) through simple landfilling or ocean dumping can result in soil and groundwater contamination, which can negatively impact ecosystem health. The case of Korea is not much different in that these wastes are simply buried or recycled wastes are used as livestock feed additives.

Study of accelerator-based epithermal neutron flux depending on Li and Be targets.

The Li(p,n) and Be(p,n) reactions are widely used as accelerator-based neutron sources for boron neutron capture therapy (BNCT). Because the energy of the neutrons produced by these reactions is high for BNCT, a moderator is required to reduce the energy to the epithermal energy region. The neutron yields and energy spectra derived from the Li(p,n) and Be(p,n) reactions vary with the incident proton energy; a high proton energy results in a high neutron yield.

Intelligent Complementary Multi-Modal Fusion for Anomaly Surveillance and Security System.

Recently, security monitoring facilities have mainly adopted artificial intelligence (AI) technology to provide both increased security and improved performance. However, there are technical challenges in the pursuit of elevating system performance, automation, and security efficiency. In this paper, we proposed intelligent anomaly detection and classification based on deep learning (DL) using multi-modal fusion.

Development of a Real-Time Pixel Array-Type Detector for Ultrahigh Dose-Rate Beams.

Although research into ultrahigh dose-rate (UHDR) radiation therapy is ongoing, there is a significant lack of experimental measurements for two-dimensional (2D) dose-rate distributions. Additionally, conventional pixel-type detectors result in significant beam loss. In this study, we developed a pixel array-type detector with adjustable gaps and a data acquisition system to evaluate its effectiveness in measuring UHDR proton beams in real time.

Inhibition of p90RSK Ameliorates PDGF-BB-Mediated Phenotypic Change of Vascular Smooth Muscle Cell and Subsequent Hyperplasia of Neointima.

Platelet-derived growth factor type BB (PDGF-BB) regulates vascular smooth muscle cell (VSMC) migration and proliferation, which play critical roles in the development of vascular conditions. p90 ribosomal S6 kinase (p90RSK) can regulate various cellular processes through many different target substrates in several cell types, but the regulatory function of p90RSK on PDGF-BB-mediated cell migration and proliferation and subsequent vascular neointima formation has not yet been extensively examined. In this study, we investigated whether p90RSK inhibition protects VSMCs against PDGF-BB-induced cellular phenotypic changes and the molecular mechanisms underlying the effect of p90RSK inhibition on neointimal hyperplasia in vivo.

Phytochemistry and Applications of Essential Oils.

Camphor tree () is an ornamental plant that has been cultivated for a long time to obtain wood or camphor. Furthermore, its essential oil can be used as an alternative medicine and is an important source of perfume. Camphor obtained from camphor trees has long been used as a treatment for various symptoms such as inflammation, infection, congestion, muscle pain, and irritation in various regions.

The complete mitochondrial genome of Patagonian moray cod, Vaillant, 1888 (Gadiformes, Muraenolepididae).

The full-length mitochondrial genome of (Vaillant, 1888) was studied using PacBio platform and it is first report in a Muraenolepididae family. The circular form of mitochondria genome is 16,833 bp including 13 protein-coding genes, two rRNA, and 22 tRNA. Start codon of 13 protein-coding genes was only ATG but three types of stop codons (TAA, T(AA), and TAG) were detected.

Cancer cell‑specific anticancer effects of Coptis chinensis on gefitinib‑resistant lung cancer cells are mediated through the suppression of Mcl‑1 and Bcl‑2.

The epidermal growth factor receptor (EGFR)‑tyrosine kinase inhibitor (TKI), gefitinib, is an effective therapeutic drug used in the treatment of non‑small cell lung cancers (NSCLCs) harboring EGFR mutations. However, acquired resistance significantly limits the efficacy of EGFR‑TKIs and consequently, the current chemotherapeutic strategies for NSCLCs. It is, therefore, necessary to overcome this resistance.

Design of compact accelerator system for high flux accelerator based neutron source.

Accelerator Based Neutron Sources (ABNS) have been studied for their utility in materials research as well as for boron neutron captured therapy. By making significant efforts to study the (p,n) and (d,n) nuclear reactions, the specifications of the accelerator system have been determined. In this paper, we compare the design results for two types of radio frequency quadrupole (RFQ) accelerators to provide proton and deuteron beams, respectively.

Publisher Correction: Development of an efficient cytosolic isobutanol production pathway in Saccharomyces cerevisiae by optimizing copy numbers and expression of the pathway genes based on the toxic effect of α-acetolactate.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Development of an efficient cytosolic isobutanol production pathway in Saccharomyces cerevisiae by optimizing copy numbers and expression of the pathway genes based on the toxic effect of α-acetolactate.

Isobutanol production in Saccharomyces cerevisiae is limited by subcellular compartmentalization of the pathway enzymes. In this study, we improved isobutanol production in S. cerevisiae by constructing an artificial cytosolic isobutanol biosynthetic pathway consisting of AlsS, α-acetolactate synthase from Bacillus subtilis, and two endogenous mitochondrial enzymes, ketol-acid reductoisomerase (Ilv5) and dihydroxy-acid dehydratase (Ilv3), targeted to the cytosol.

Efficient production of lycopene in Saccharomyces cerevisiae by enzyme engineering and increasing membrane flexibility and NAPDH production.

Lycopene is a red carotenoid pigment with strong antioxidant activity. Saccharomyces cerevisiae is considered a promising host to produce lycopene, but lycopene toxicity is one of the limiting factors for high-level production. In this study, we used heterologous lycopene biosynthesis genes crtE and crtI from Xanthophyllomyces dendrorhous and crtB from Pantoea agglomerans for lycopene production in S.

Resistance to gefitinib and cross-resistance to irreversible EGFR-TKIs mediated by disruption of the Keap1-Nrf2 pathway in human lung cancer cells.

The development of resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) occurs by various mechanisms and appears to be almost inevitable, even in patients with lung cancer who initially respond well to EGFR-TKIs. Consequently, considerable efforts have been made to develop more effective EGFR-TKIs. Therefore, an understanding of the mechanisms behind TKI resistance is essential for improving EGFR-TKI therapeutic efficacy in non-small cell lung cancer (NSCLC) patients.

Topical Treatment for Cutaneous Leishmaniasis: Dermato-Pharmacokinetic Lead Optimization of Benzoxaboroles.

Cutaneous leishmaniasis (CL) is caused by several species of the protozoan parasite , affecting an estimated 10 million people worldwide. Previously reported strategies for the development of topical CL treatments have focused primarily on drug permeation and formulation optimization as the means to increase treatment efficacy. Our approach aims to identify compounds with antileishmanial activity and properties consistent with topical administration.

THz-pump and X-ray-probe sources based on an electron linac.

We describe a compact THz-pump and X-ray-probe beamline, based on an electron linac, for ultrafast time-resolved diffraction applications. Two high-energy electron (γ > 50) bunches, 5 ns apart, impinge upon a single-foil or multifoil radiator and generate THz radiation and X-rays simultaneously. The THz pulse from the first bunch is synchronized to the X-ray beam of the second bunch by using an adjustable optical delay of a THz pulse.

Preclinical Pharmacokinetics and Pharmacodynamic Target of SCY-078, a First-in-Class Orally Active Antifungal Glucan Synthesis Inhibitor, in Murine Models of Disseminated Candidiasis.

SCY-078 (MK-3118) is a novel, semisynthetic derivative of enfumafungin and represents the first compound of the triterpene class of antifungals. SCY-078 exhibits potent inhibition of β-(1,3)-d-glucan synthesis, an essential cell wall component of many pathogenic fungi, including spp. and spp.

Mammalian knock out cells reveal prominent roles for atlastin GTPases in ER network morphology.

Atlastins are large, membrane-bound GTPases that participate in the fusion of endoplasmic reticulum (ER) tubules to generate the polygonal ER network in eukaryotes. They also regulate lipid droplet size and inhibit bone morphogenetic protein (BMP) signaling, though mechanisms remain unclear. Humans have three atlastins (ATL1, ATL2, and ATL3), and ATL1 and ATL3 are mutated in autosomal dominant hereditary spastic paraplegia and hereditary sensory neuropathies.

Improvement of isobutanol production in Saccharomyces cerevisiae by increasing mitochondrial import of pyruvate through mitochondrial pyruvate carrier.

Subcellular compartmentalization of the biosynthetic enzymes is one of the limiting factors for isobutanol production in Saccharomyces cerevisiae. Previously, it has been shown that mitochondrial compartmentalization of the biosynthetic pathway through re-locating cytosolic Ehrlich pathway enzymes into the mitochondria can increase isobutanol production. In this study, we improved mitochondrial isobutanol production by increasing mitochondrial pool of pyruvate, a key substrate for isobutanol production.

Development of an S-band cavity-type beam position monitor for a high power THz free-electron laser.

A cavity-type beam position monitor (BPM) has been developed for a compact terahertz (THz) free-electron laser (FEL) system and ultra-short pulsed electron Linac system at the Korea Atomic Energy Research Institute (KAERI). Compared with other types of BPMs, the cavity-type BPM has higher sensitivity and faster response time even at low charge levels. When electron beam passes through the cavity-type BPM, it excites the dipole mode of the cavity of which amplitude depends linearly on the beam offset from the center of the cavity.

In vitro metabolism, permeability, and efflux of bazedoxifene in humans.

Bazedoxifene (BZA) acetate, a novel estrogen receptor modulator being developed for the prevention and treatment of postmenopausal osteoporosis, undergoes extensive metabolism in women after oral administration. In this study, the in vitro metabolism of [(14)C]BZA was determined in human hepatocytes and hepatic and intestinal microsomes, and the UDP glucuronosyltransferase (UGT) isozymes involved in the glucuronidation of BZA were identified. In addition, BZA was evaluated for its potential as a substrate of P-glycoprotein (P-gp) transporter in Caco-2 cell monolayers.

Identification of a tolerant locus on Arabidopsis thaliana to hypervirulent beet curly top virus CFH strain.

The infection of hosts by the geminivirus depends on the interactions between host and viral factors for viral DNA replication, viral gene expression, and the movement of virus throughout the hosts. This work reports that a hypervirulent strain of Beet curly top virus (BCTV) is different in its ability to infect several ecotypes of Arabidopsis thaliana. Symptoms appeared on Arabidopsis ecotypes around 7 to 10 d after inoculation with BCTV-CFH.