Genetic Incorporation of a Thioxanthone-Containing Amino Acid for the Design of Artificial Photoenzymes.

Genetically encodable photosensitizers allow the design of artificial photoenzymes to expand the scope of abiological reactions. Herein, we report the genetic incorporation of a thioxanthone-containing amino acid into a protein scaffold via an engineered pyrrolysyl-tRNA/pyrrolysyl-tRNA synthetase pair. The designer enzyme was engineered to catalyze a dearomative [2+2] cycloaddition reaction in high yields (up to>99 % yield) with excellent enantioselectivity (up to 98 : 2 e.

Dual-Enhanced SERS Satellite Immuno-Nanocomplex for Multiple PSA-Mediated PHI Assay Toward Clinical Prostate Cancer Screening.

Prostate specific antigen (PSA) is widely used in liquid biopsy of prostate cancer (PCa) but still faces challenges due to the poor specificity. Herein, this study reports a double-SERS satellite immunoassay, made of an Au-Ag dealloyed intra-nanogap nanoflower (Au-Ag DINF) with strong SERS signals and Au magnetic nanoparticles (AuMNPs) with magnetic capture and SERS amplification, for sensing multiple PSA (free PSA (fPSA), complexed PSA (cPSA) and [-2]proPSA (p2PSA)) toward potential PCa screening. Unlike the previous studies focus on the tPSA and fPSA/tPSA ratio (f/t PSA%), this work introduces a multiple PSA-mediated Prostate Health Index (PHI) assay with significantly increased the predictive accuracy and specificity of PCa, especially the patients with a tPSA level in the "diagnostic gray zone".

ClustAll: An R package for patient stratification in complex diseases.

In the era of precision medicine, it is necessary to understand heterogeneity among patients with complex diseases to improve personalized prevention and management strategies. Here, we introduce ClustAll, a Bioconductor package designed for unsupervised patient stratification using clinical data. ClustAll is based on the previously validated methodology ClustAll, a clustering framework that effectively handles intricacies in clinical data, including mixed data types, missing values, and collinearity.

Correction and removal of expression of concern: Enhancement of anti-leukemic potential of 2-hydroxyphenyl-azo-2'-naphthol (HPAN) on MOLT-4 cells through conjugation with Cu(ii).

[This corrects the article DOI: 10.1039/C3RA44765K.].

Antibacterial and safe chitosan-graphene hydrogel films: a promising nanotherapeutic for wound infections.

Pathogenic bacterial growth at wound sites, particularly , poses a serious threat during trauma. Delayed treatment can lead to increased inflammation and severe tissue damage. In this study, a chitosan cross-linked polycationic peptide-conjugated graphene-silver (CGrAP) nanocomposite hydrogel film was developed as an antibacterial wound dressing to treat infections.

Rounded Turn SLIM Design for High-Resolution Ion Mobility Mass Spectrometry Analysis of Small Molecules.

Various rounded turn designs in Structures for Lossless Ion Manipulation (SLIM) were explored via ion trajectory simulations. The optimized design was integrated into a SLIM ion mobility (IM) system coupled with a time-of-flight (TOF) mass spectrometer (MS) for further experimental investigation. The SLIM-TOF IM-MS system was assessed for IM resolution and ion transmission efficiency across a wide / range using various RF frequencies and buffer gas combinations.

The histidine kinase NahK regulates denitrification and nitric oxide accumulation through RsmA in .

Unlabelled: have a versatile metabolism; they can adapt to many stressors, including limited oxygen and nutrient availability. This versatility is especially important within a biofilm where multiple microenvironments are present. As a facultative anaerobe, can survive under anaerobic conditions utilizing denitrification.

Discovery of VU0467319: an M Positive Allosteric Modulator Candidate That Advanced into Clinical Trials.

Herein we detail the of VU0467319 (VU319), an M Positive Allosteric Modulator (PAM) clinical candidate that successfully completed a Phase I Single Ascending Dose (SAD) clinical trial. VU319 () is a moderately potent M PAM (M PAM EC = 492 nM ± 2.9 nM, 71.

Total biosynthesis of cotylenin diterpene glycosides as 14-3-3 protein-protein interaction stabilizers.

Cotylenins (CNs) are bioactive fungal diterpene glycosides that exhibit stabilizing activity on 14-3-3 protein-protein interactions (PPIs), which has significant therapeutic potential. Although CNs were isolated as early as 1970, their biosynthetic pathway has remained unclear, and their limited supply has hindered further research. Here, we report the identification of the biosynthetic gene cluster and elucidation of the biosynthetic pathway of CNs.

Evidence of "Silent" Hepatitis B Virus Infection in Psoriasis, Vitiligo, and Cases: A Pilot Study.

Background: Psoriasis (PS), vitiligo (VT), and (PR) are chronic skin diseases often occurring as a consequence of exaggerated immune responses. These skin manifestations can be triggered as a result of the molecular mimicry between viral protein (s) and host protein (s), which could generate auto-antibodies. In addition, it can be hypothesised that skin diseases are manifestations of the reduced immunity that is observed in chronic hepatitis B virus (HBV)-infected individuals.

Interplay between Energy and Entropy Mediates Ambimodal Selectivity of Cycloadditions.

One ambimodal transition state can lead to the formation of multiple products. However, it remains fundamentally unknown how the energy and entropy along the post-TS pathways mediate ambimodal selectivity. Here, we investigated the energy and entropy profiles along the post-TS pathways in four [4 + 2]/[6 + 4] cycloadditions.

Preventing epileptogenesis by interaction between inositol isomers and proteins.

Objective: Inositols play significant roles in biological systems. Myo-inositol (MI), the most prevalent isomer, functions as an osmolyte and mediates cell signal transduction. Other notable isomers include Scyllo-inositol (SCI) and D-Chiro-inositol (DCHI).

Preparation and characterization of mangiferin-loaded polylactic acid nanofiber mat with antioxidant and anti-browning properties for the development of food packaging products.

In this study, antioxidant nanofiber-based food packaging material composed of polylactic acid (PLA) and mangiferin (MG) was produced to reduce food spoilage. To this end, MG was extracted from Mangifera indica and chemically characterized. In vitro assays for scavenging several radical ions showed excellent antioxidant properties of MG.

Application of a modified lactate dehydrogenase assay to evaluate the viability of cells cultured on 3D scaffolds when commonly used assays fail.

The development of new compounds or materials for medicine suggests a study of their cytotoxicity. The effect of a material on cell viability can be evaluated by several methods based on DNA content, DNA synthesis, plasma membrane integrity, cellular enzyme activity, cellular reducing potential, and ATP level. Sometimes it is impossible to apply widely used commercially available reagents, e.

Encage the Carcinogens: A Metal-"Organic Cage" Framework for Efficient Polycyclic Aromatic Hydrocarbon Removal From Water.

Polycyclic aromatic hydrocarbons (PAHs) are carcinogenic and persistent organic pollutants in water. Their removal is highly challenging for existing generic and nonspecific adsorbents, creating an urgent need for tailored solutions. Herein, a metal-"organic cage" framework, MOF-CC-1, designed for the effective scavenging of PAHs from water is is introduced.

Advancements in Loop Cyclization Approaches for Enhanced Peptide Therapeutics for Targeting Protein-Protein Interactions.

Protein-protein interactions (PPIs) are pivotal in regulating cellular functions and life processes, making them promising therapeutic targets in modern medicine. Despite their potential, developing PPI inhibitors poses significant challenges due to their large and shallow interfaces that complicate ligand binding. This study focuses on mimicking peptide loops as a strategy for PPI inhibition, utilizing synthetic peptide loops for replicating critical binding regions.

Semaphorins and its receptors: Emerging cellular biomarkers and therapeutic targets in autoimmune and inflammatory disorders.

Semaphorins have been discovered to play an array of roles in immune regulation, especially in the complex field of inflammatory and autoimmune disorders. Originally discovered for their critical role in directing axon growth during brain development, semaphores have since been shown to have versatile actions. They are distinguished by a conserved extracellular sema domain with a 7-blade beta propeller structure.

WelQrate: Defining the Gold Standard in Small Molecule Drug Discovery Benchmarking.

While deep learning has revolutionized computer-aided drug discovery, the AI community has predominantly focused on model innovation and placed less emphasis on establishing best benchmarking practices. We posit that without a sound model evaluation framework, the AI community's efforts cannot reach their full potential, thereby slowing the progress and transfer of innovation into real-world drug discovery. Thus, in this paper, we seek to establish a new gold standard for small molecule drug discovery benchmarking, .

Aggregation of Transthyretin by Fluid Agitation.

The transthyretin (TTR) tetramer, assembled as a dimer of dimers, transports thyroxine and retinol binding protein in blood plasma and cerebrospinal fluid. Aggregation of wild type or pathogenic variant TTR leads to transthyretin amyloidosis (ATTR), which is associated with neurodegenerative and cardiac disease. The trigger for TTR aggregation under physiological conditions is unknown.

Computational Evidence for Bisartan Arginine Blockers as Next-Generation Pan-Antiviral Therapeutics Targeting SARS-CoV-2, Influenza, and Respiratory Syncytial Viruses.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, and respiratory syncytial virus (RSV) are significant global health threats. The need for low-cost, easily synthesized oral drugs for rapid deployment during outbreaks is crucial. Broad-spectrum therapeutics, or pan-antivirals, are designed to target multiple viral pathogens simultaneously by focusing on shared molecular features, such as common metal cofactors or conserved residues in viral catalytic domains.

Using Computer Modeling and Experimental Methods to Screen for Aptamers That Bind to the VV-GMCSF-LACT Virus.

Oncolytic virotherapy is a promising approach for cancer treatment. However, when introduced into the body, the virus provokes the production of virus-neutralizing antibodies, which can reduce its antitumor effect. To shield viruses from the immune system, aptamers that can cover the membrane of the viral particle are used.