Fatty Acid Derivatization and Cyclization of the Immunomodulatory Peptide RP-182 Targeting CD206high Macrophages Improve Antitumor Activity.

As tumor-associated macrophages (TAM) exercise a plethora of protumor and immune evasive functions, novel strategies targeting TAMs to inhibit tumor progression have emerged within the current arena of cancer immunotherapy. Activation of the mannose receptor 1 (CD206) is a recent approach that recognizes immunosuppressive CD206high M2-like TAMs as a drug target. Ligation of CD206 both induces reprogramming of CD206high TAMs toward a proinflammatory phenotype and selectively triggers apoptosis in these cells.

Afraid and tired: A longitudinal study of the relationship between cancer-related fatigue and fear of cancer recurrence in long-term cancer survivors.

Objective: Cancer-related fatigue (CRF) and fear of cancer recurrence (FCR) are two common concerns experienced by cancer survivors. However, the relationship between these two concerns is poorly understood, and whether CRF and FCR influence each other over time is unclear.

Methods: Data were from a national, prospective, longitudinal study, the American Cancer Society's Study of Cancer Survivors-I (SCS-I).

Perfluorinated Iridium Catalyst for Signal Amplification by Reversible Exchange Provides Metal-Free Aqueous Hyperpolarized [1-C]-Pyruvate.

Hyperpolarized (HP) carbon-13 [C] enables the specific investigation of dynamic metabolic and physiologic processes via in vivo MRI-based molecular imaging. As the leading HP metabolic agent, [1-C]pyruvate plays a pivotal role due to its rapid tissue uptake and central role in cellular energetics. Dissolution dynamic nuclear polarization (d-DNP) is considered the gold standard method for the production of HP metabolic probes; however, development of a faster, less expensive technique could accelerate the translation of metabolic imaging via HP MRI to routine clinical use.

Comparative Analysis of Drug-like EP300/CREBBP Acetyltransferase Inhibitors.

The human acetyltransferase paralogues EP300 and CREBBP are master regulators of lysine acetylation whose activity has been implicated in various cancers. In the half-decade since the first drug-like inhibitors of these proteins were reported, three unique molecular scaffolds have taken precedent: an indane spiro-oxazolidinedione (A-485), a spiro-hydantoin (iP300w), and an aminopyridine (CPI-1612). Despite increasing use of these molecules to study lysine acetylation, the dearth of data regarding their relative biochemical and biological potencies makes their application as chemical probes a challenge.

Auranofin targets UBA1 and enhances UBA1 activity by facilitating ubiquitin trans-thioesterification to E2 ubiquitin-conjugating enzymes.

UBA1 is the primary E1 ubiquitin-activating enzyme responsible for generation of activated ubiquitin required for ubiquitination, a process that regulates stability and function of numerous proteins. Decreased or insufficient ubiquitination can cause or drive aging and many diseases. Therefore, a small-molecule enhancing UBA1 activity could have broad therapeutic potential.

Comparative analysis of drug-like EP300/CREBBP acetyltransferase inhibitors.

The human acetyltransferase paralogs EP300 and CREBBP are master regulators of lysine acetylation whose activity has been implicated in various cancers. In the half-decade since the first drug-like inhibitors of these proteins were reported, three unique molecular scaffolds have taken precedent: an indane spiro-oxazolidinedione (A-485), a spiro-hydantoin (iP300w), and an aminopyridine (CPI-1612). Despite increasing use of these molecules to study lysine acetylation, the dearth of data regarding their relative biochemical and biological potencies makes their application as chemical probes a challenge.

An approach to rapid distributed manufacturing of broad spectrum anti-viral griffithsin using cell-free systems to mitigate pandemics.

This study describes the cell-free biomanufacturing of a broad-spectrum antiviral protein, griffithsin (GRFT) such that it can be produced in microgram quantities with consistent purity and potency in less than 24 h. We demonstrate GRFT production using two independent cell-free systems, one plant and one microbial. Griffithsin purity and quality were verified using standard regulatory metrics.

Sensory quality of Citrus scion hybrids with Poncirus trifoliata in their pedigrees.

Hybrids of Poncirus trifoliata L. Raf. with Citrus have shown degrees of tolerance to the deadly citrus greening disease, hence prompting interest as potential commercial varieties.

An approach to rapid distributed manufacturing of broad spectrum anti-viral griffithsin using cell-free systems to mitigate pandemics.

This study describes the cell-free biomanufacturing of a broad-spectrum antiviral protein, griffithsin (GRFT) such that it can be produced with consistent purity and potency in less than 24 hours. We demonstrate GRFT production using two independent cell-free systems, one plant and one microbial. Griffithsin purity and quality were verified using standard regulatory metrics.

Long-lasting insecticidal nets provide protection against malaria for only a single year in Burundi, an African highland setting with marked malaria seasonality.

Background: Long-lasting insecticidal nets (LLINs) are one of the key interventions in the global fight against malaria. Since 2014, mass distribution campaigns of LLINs aim for universal access by all citizens of Burundi. In this context, we assess the impact of LLINs mass distribution campaigns on malaria incidence, focusing on the endemic highland health districts.

Discovery of Novel Small-Molecule Scaffolds for the Inhibition and Activation of WIP1 Phosphatase from a RapidFire Mass Spectrometry High-Throughput Screen.

Wild-type P53-induced phosphatase 1 (WIP1), also known as or PP2Cδ, is a serine/threonine protein phosphatase induced by P53 after genotoxic stress. WIP1 inhibition has been proposed as a therapeutic strategy for P53 wild-type cancers in which it is overexpressed, but this approach would be ineffective in P53-negative cancers. Furthermore, there are several cancers with mutated P53 where WIP1 acts as a tumor suppressor.

A small-molecule inhibitor and degrader of the RNF5 ubiquitin ligase.

RNF5 E3 ubiquitin ligase has multiple biological roles and has been linked to the development of severe diseases such as cystic fibrosis, acute myeloid leukemia, and certain viral infections, emphasizing the importance of discovering small-molecule RNF5 modulators for research and drug development. The present study describes the synthesis of a new benzo[]thiophene derivative, FX12, that acts as a selective small-molecule inhibitor and degrader of RNF5. We initially identified the previously reported STAT3 inhibitor, Stattic, as an inhibitor of dislocation of misfolded proteins from the endoplasmic reticulum (ER) lumen to the cytosol in ER-associated degradation.

Structure-Based Optimization of Small Molecule Human Galactokinase Inhibitors.

Classic galactosemia is a rare disease caused by inherited deficiency of galactose-1 phosphate uridylyltransferase (GALT). Accumulation of galactose-1 phosphate (gal-1P) is thought to be the major cause of the chronic complications associated with this disease, which currently has no treatment. Inhibiting galactokinase (GALK1), the enzyme that generates galactose-1 phosphate, has been proposed as a novel strategy for treating classic galactosemia.

Novel sampling methods for monitoring from Eritrea.

Background: Studies comparing novel collection methods for host seeking and resting mosquitoes were undertaken in a village in Eritrea. Techniques included an odor baited trap, a novel tent-trap, human landing collection and three methods of resting collection. A technique for the collection of mosquitoes exiting vegetation is also described.

A Universal and High-Throughput Proteomics Sample Preparation Platform.

Major advances have been made to improve the sensitivity of mass analyzers, spectral quality, and speed of data processing enabling more comprehensive proteome discovery and quantitation. While focus has recently begun shifting toward robust proteomics sample preparation efforts, a high-throughput proteomics sample preparation is still lacking. We report the development of a highly automated universal 384-well plate sample preparation platform with high reproducibility and adaptability for extraction of proteins from cells within a culture plate.

Comparing Vestibule Examination Techniques: Light Touch, Serial Forces, and the Lidocaine Test.

Objective: The purpose of this study was to compare techniques and pain scales that assess tenderness in the vulvar vestibule in provoked vestibulodynia, using the cotton swab test and a vulvalgesiometer, and assess topical lidocaine solution with each.

Materials And Methods: This randomized study at a specialty vulvar clinic evaluated tender vestibules of reproductive-aged women with vestibulodynia using light rolling cotton swab touch at 6 sites and evaluated the vulvalgesiometer at 2 sites, randomizing the order of the initial tool. Participants reported pain using the Numerical Rating Scale 0-10 and the Verbal Pain Scale 0-3.

High-throughput protein modification quantitation analysis using intact protein MRM and its application on hENGase inhibitor screening.

Proteins are widely used as drug targets, enzyme substrates, and biomarkers for numerous diseases. The emerging demand for proteins quantitation has been increasing in multiple fields. Currently, there is still a big gap for high-throughput protein quantitation at intact protein level using label-free method.

A direct peptide reactivity assay using a high-throughput mass spectrometry screening platform for detection of skin sensitizers.

Chemical-peptide conjugation is the molecular initiating event in skin sensitization. The OECD test guideline uses a high-performance liquid chromatography/ultraviolet (HPLC/UV) detection method to quantify chemical-peptide conjugation in a direct peptide reactivity assay (DPRA), which measures the depletion of two synthetic peptides containing lysine or cysteine residues. To improve assay throughput, sensitivity and accuracy, an automated 384-well plate-based RapidFire solid-phase extraction (SPE) system coupled with tandem mass spectrometry (MS/MS) DPRA was developed and validated in the presence of a newly designed internal standard.

Health anxiety and illness-related fears across diverse chronic illnesses: A systematic review on conceptualization, measurement, prevalence, course, and correlates.

Background: Patients with chronic diseases commonly report fears of illness or symptoms recurring or worsening. These fears have been addressed from an illness-specific perspective (e.g.

Effect of fruit maturity on volatiles and sensory descriptors of four mandarin hybrids.

Mandarins (or tangerines) are mainly consumed as fresh fruits due to the ease of peeling and desirable flavor. Sweetness, acidity, and flavor of mandarin are the most important criteria for consumer preference. The objective of this study was to evaluate the effects of harvest date on sensory and chemical components of four mandarin cultivars (Murcott, 411, Temple, and 'LB8-9' Sugar Belle®).