The pons as an optimal background reference region for spinal F-FET PET/MRI evaluation.

Background: This study aims to evaluate the effect of various background reference regions on spinal F-FET PET imaging, with a focus on distinguishing between spinal tumors and myelitis. To enhance diagnostic accuracy, we investigated the pons and several other spinal cord area as potential references, given the challenges in interpreting spinal PET results.

Results: A retrospective analysis was conducted on 30 patients, 15 with cervical myelitis and 15 with cervical tumors, who underwent O-(2-[F]-fluoroethyl)-L-tyrosine (FET) PET/MR imaging.

Diffusion Tensor Imaging Identifies Cervical Spondylosis, Myelitis, and Spinal Cord Tumors.

Background: Diffusion tensor imaging (DTI) has been increasingly recognized for its capability to study microstructural changes in the neuropathology of brain diseases. However, the optimal DTI metric and its diagnostic utility for a variety of spinal cord diseases are still under investigation.

Purpose: To evaluate the diagnostic efficacy of DTI metrics for differentiating between cervical spondylosis, myelitis, and spinal tumors.

Screening through Lead Optimization of High Affinity, Allosteric Cyclin-Dependent Kinase 2 (CDK2) Inhibitors as Male Contraceptives That Reduce Sperm Counts in Mice.

Although cyclin-dependent kinase 2 (CDK2) is a validated target for both cancer and contraception, developing a CDK2 inhibitor with exquisite selectivity has been challenging due to the structural similarity of the ATP-binding site, where most kinase inhibitors bind. We previously discovered an allosteric pocket in CDK2 with the potential to bind a selective compound and then discovered and structurally confirmed an anthranilic acid scaffold that binds this pocket with high affinity. These allosteric inhibitors are selective for CDK2 over structurally similar CDK1 and show contraceptive potential.

Population genetic structure of highlights the necessity and feasibility of hierarchical analysis for a highly differentiated species.

Population genetic structure can provide valuable insights for conserving genetic resources and understanding population evolution, but it is often underestimated when using the most popular method and software, STRUCTURE and delta K, to assess. Although the hierarchical STRUCTURE analysis has been proposed early to overcome the above potential problems, this method was just utilized in a few studies and its reliability needs to be further tested. In this study, the genetic structure of populations of was evaluated by sequencing 12 nuclear microsatellite loci of 905 individuals from 38 populations.

Effects of land use change on population survival of three wild rice species in China since 2001.

Land use change stemming from human activities, particularly cropland expansion, heavily threatens the survival of crop wild relatives that usually occur nearby or scatter in farming systems. Understanding the impacts of land use change on wild populations is critical in forming the conservation decision-making of wild relatives. Based on the investigations on the population survival of three wild rice species (, , and ) in China over the past 40 years (1978-2019), the effect of land use change during the past 20 years (2001-2019) on the natural populations of the three species was examined using the land use type data of satellite-based Earth observations (data from GlobCover).

The effect of Q.Clear reconstruction on quantification and spatial resolution of 18F-FDG PET in simultaneous PET/MR.

Background: Q.Clear is a block sequential regularized expectation maximization penalized-likelihood reconstruction algorithm for Positron Emission Tomography (PET). It has shown high potential in improving image reconstruction quality and quantification accuracy in PET/CT system.

FBNTI, a DOR-Selective Antagonist That Allosterically Activates MOR within a MOR-DOR Heteromer.

This report describes the unique pharmacological profile of FBNTI, a potent DOR antagonist that acts as a MOR agonist via an allosteric mechanism. Binding of FBNTI to opioid receptors expressed in HEK 293 cells revealed a 190-fold greater affinity for DOR ( = 0.84 nM) over MOR ( = 160 nM).

Cooperativity Between Orthosteric Inhibitors and Allosteric Inhibitor 8-Anilino-1-Naphthalene Sulfonic Acid (ANS) in Cyclin-Dependent Kinase 2.

While kinases have been attractive targets to combat many diseases, including cancer, selective kinase inhibition has been challenging, because of the high degree of structural homology in the active site, where many kinase inhibitors bind. We have previously discovered that 8-anilino-1-naphthalene sulfonic acid (ANS) binds an allosteric pocket in cyclin-dependent kinase 2 (Cdk2). Here, we detail the positive cooperativity between ANS and orthosteric Cdk2 inhibitors dinaciclib and roscovitine, which increase the affinity of ANS toward Cdk2 5-fold to 10-fold, and the relatively noncooperative effects of ATP.

Human Adenine Nucleotide Translocase (ANT) Modulators Identified by High-Throughput Screening of Transgenic Yeast.

Transport of ADP and ATP across mitochondria is one of the primary points of regulation to maintain cellular energy homeostasis. This process is mainly mediated by adenine nucleotide translocase (ANT) located on the mitochondrial inner membrane. There are four human ANT isoforms, each having a unique tissue-specific expression pattern and biological function, highlighting their potential as drug targets for diverse clinical indications, including male contraception and cancer.

High-throughput screening for growth inhibitors using a yeast model of familial paraganglioma.

Classical tumor suppressor genes block neoplasia by regulating cell growth and death. A remarkable puzzle is therefore presented by familial paraganglioma (PGL), a neuroendocrine cancer where the tumor suppressor genes encode subunits of succinate dehydrogenase (SDH), an enzyme of the tricarboxylic acid (TCA) cycle of central metabolism. Loss of SDH initiates PGL through mechanisms that remain unclear.

Structure-activity relationship and molecular mechanisms of ethyl 2-amino-4-(2-ethoxy-2-oxoethyl)-6-phenyl-4h-chromene-3-carboxylate (sha 14-1) and its analogues.

Rapid development of multiple drug resistance against current therapies is a major barrier in the treatment of cancer. Therefore, anticancer agents that can overcome acquired drug resistance in cancer cells are of great importance. Previously, we have demonstrated that ethyl 2-amino-4-(2-ethoxy-2-oxoethyl)-6-phenyl-4H-chromene-3-carboxylate (5a, sHA 14-1), a stable analogue of ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate (6, HA 14-1), mitigates drug resistance and synergizes with a variety of cancer therapies in leukemia cells.

WL-276, an antagonist against Bcl-2 proteins, overcomes drug resistance and suppresses prostate tumor growth.

Patients with hormone-refractory prostate cancer (HRPC) have an estimated median survival of only 10 months because of acquired drug resistance, urging the need to develop therapies against the drug-resistant HRPC phenotype. Accumulating evidence suggests that overexpressing antiapoptotic Bcl-2 family proteins is at least partially responsible for the development of drug resistance among HRPC patients. Antagonizing the antiapoptotic Bcl-2 family proteins, therefore, is one potential approach to circumventing drug resistance in HRPC.

sHA 14-1, a stable and ROS-free antagonist against anti-apoptotic Bcl-2 proteins, bypasses drug resistances and synergizes cancer therapies in human leukemia cell.

HA 14-1, a small-molecule antagonist against anti-apoptotic Bcl-2 proteins, was demonstrated to induce selective cytotoxicity toward malignant cells and to overcome drug resistance. Due to its poor stability and the reactive oxygen species (ROS) generated by its decomposition, chemical modification of HA 14-1 is needed for its future development. We have synthesized a stabilized analog of HA 14-1--sHA 14-1, which did not induce the formation of ROS.

Ethyl-2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H- chromene-3-carboxylate (HA 14-1), a prototype small-molecule antagonist against antiapoptotic Bcl-2 proteins, decomposes to generate reactive oxygen species that induce apoptosis.

Overexpressing antiapoptotic Bcl-2 proteins to suppress apoptosis is one major mechanism via which cancer cells acquire drug resistance against cancer therapy. Ethyl-2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4 H-chromene-3-carboxylate (HA 14-1) is one of the earliest small-molecule antagonists against antiapoptotic Bcl-2 proteins. Since its discovery, HA 14-1 has been shown to be able to synergize a variety of anticancer agents.

Structure-activity relationship studies of ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate (HA 14-1), an antagonist for antiapoptotic Bcl-2 proteins to overcome drug resistance in cancer.

The structure-activity relationship studies of ethyl 2-amino-6-cyclopentyl-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate (1, HA 14-1), an antagonist of the antiapoptotic Bcl-2 proteins, are reported. A series of analogues of 1 with varied functional groups at the 6-position of the chromene ring were synthesized. These candidates were evaluated for their binding interactions with three antiapoptotic proteins: Bcl-2, Bcl-XL, and Bcl-w.

Development of a new high-throughput screening model for human high density lipoprotein receptor (CLA-1) agonists.

Objective: To develop a new high-throughput screening model for human high-density lipoprotein (HDL) receptor (CD36 and LIMPII analogous-1, CLA-1) agonists using CLA-1-expressing insect cells.

Methods: With the total RNA of human hepatoma cells BEL-7402 as template, the complementary DNA (cDNA) of CLA-1 was amplified by reverse transcription-polymerase chain reaction (RT-PCR). Bac-to-Bac baculovirus expression system was used to express CLA-1 in insect cells.