Single-Molecule Oxidoreductase Activity Analysis for Activity-Based Diagnosis Based on Proteoform Alterations.

We developed a single-molecule enzyme activity assay platform for NAD(P)-dependent oxidoreductases, leveraging a new NAD(P)H-responsive fluorogenic probe optimized for microdevice-based fluorometric detection. This platform enabled the detection of enzyme activities in blood and cerebrospinal fluid (CSF), including lactate dehydrogenase, glucose-6-phosphate dehydrogenase, and hexokinases. We demonstrate its potential for activity-based diagnosis by detecting altered populations of enzyme activity species in blood and CSF from liver damage in brain tumor patients.

Legionnaires' Disease Presenting With Acute Kidney Injury: Successful Treatment With Antibiotics.

Legionnaires' disease is a bacterial infection caused by , such as . It mainly causes severe pneumonia, with symptoms such as fever, cough, and shortness of breath. In rare cases, it can cause acute kidney disease and also occasionally become severe enough to require replacement therapy.

Backbone resonance assignments of the C-terminal thioesterase domain of tyrocidine synthetase C.

Natural macrocyclic peptides produced by microorganisms serve as valuable resources for therapeutic compounds, including antibiotics, anticancer agents, and immune suppressive agents. Nonribosomal peptide synthetases (NRPSs) are responsible for the biosynthesis of macrocyclic peptides. NRPSs are large multimodular enzymes, and each module recognizes and incorporates one specific amino acid into the polypeptide product.

Local QSAR based on quantum chemistry calculations for the stability of nitrenium ions to reduce false positive outcomes from standard QSAR systems for the mutagenicity of primary aromatic amines.

Background: Primary aromatic amines (PAAs) present significant challenges in the prediction of mutagenicity using current standard quantitative structure activity relationship (QSAR) systems, which are knowledge-based and statistics-based, because of their low positive prediction values (PPVs). Previous studies have suggested that PAAs are metabolized into genotoxic nitrenium ions. Moreover, ddE, a relative-energy based index derived from quantum chemistry calculations that measures the stability nitrenium ions, has been correlated with mutagenicity.

Individualized tacrolimus therapy: Insights from CYP3A5 polymorphisms and intestinal metabolism.

CYP3A4 and CYP3A5 are the most abundant and important enzymes of the CYP3A subfamily, distributed in the liver, intestinal mucosa and kidney, and involved in tacrolimus metabolism. Here, we report a case of tacrolimus dosage refractoriness due to a genetic polymorphism of

Direct evidence for a deprotonated lysine serving as a H-bond "acceptor" in a photoreceptor protein.

Deprotonation or suppression of the pa of the amino group of a lysine sidechain is a widely recognized phenomenon whereby the sidechain amino group transiently can act as a nucleophile at the active site of enzymatic reactions. However, a deprotonated lysine and its molecular interactions have not been directly experimentally detected. Here, we demonstrate a deprotonated lysine stably serving as an "acceptor" in a H-bond between the photosensor protein RcaE and its chromophore.

Convenient screening of the reproductive toxicity of favipiravir and antiviral drugs in .

Reproductive toxicity is one of the major concerns in drug development. Thus, we have developed its screening system using which has a life cycle of three days and similar coding genes as humans. Antiviral nucleoside analogs used for acute infections are known to cause reproductive toxicity, contraindicated for pregnant women, and are used for comparing their reproductive toxicity in and experimental animals.

Fatty acids and volatile compound of cooked green licuri (Syagrus coronata) and naturally ripe licuri almonds from native flora, popularly consumed in Brazil.

The present study was carried out to investigate the proximate composition, fatty acid (FA) profile and volatile compounds (VC) of cooked green licuri (Syagrus coronata) - an unripe stage that is then cooked - and naturally ripe licuri almonds. The FA profiles were determined by gas chromatography (GC) and the VC composition was evaluated using headspace-solid-phase microextraction coupled with GC-MS. The cooked green licuri presented higher moisture, and lower contents of ashes, proteins and lipids than naturally ripe licuri almonds.

Single-Shot Single-Mode Optical Two-Parameter Displacement Estimation beyond Classical Limit.

Uncertainty principle prohibits the precise measurement of both components of displacement parameters in phase space. We have theoretically shown that this limit can be beaten using single-photon states, in a single-shot and single-mode setting [F. Hanamura et al.

Considerations for the genotoxicity assessment of middle size peptide drugs containing non-canonical amino acid residues.

Background: Middle size peptides (MSPs) have emerged as a promising new pharmaceutical modality. We are seeking the best way to assess the non-clinical safety of MSPs.

Consideration: The requirements for assessing the genotoxicity of pharmaceuticals differ between small molecule drugs and biotherapeutics.

A monomeric StayGold fluorescent protein.

StayGold is an exceptionally bright and stable fluorescent protein that is highly resistant to photobleaching. Despite favorable fluorescence properties, use of StayGold as a fluorescent tag is limited because it forms a natural dimer. Here we report the 1.

Rapid assessment of the immunogenicity potential of engineered antibody therapeutics through detection of CD4 T cell interleukin-2 secretion.

Therapeutic antibodies sometimes elicit anti-drug antibodies (ADAs) that can affect efficacy and safety. Engineered antibodies that contain artificial amino acid sequences are potentially highly immunogenic, but this is currently difficult to predict. Therefore, it is important to efficiently assess immunogenicity during the development of complex antibody-based formats.

Chia Phenolic Extract Appear to Improve Small Intestinal Functionality, Morphology, Bacterial Populations, and Inflammation Biomarkers In Vivo ().

Phenolic compounds can act as a substrate for colonic resident microbiota. Once the metabolites are absorbed and distributed throughout the body, they can have diverse effects on the gut. The objective of this study was to evaluate the effects of the intra-amniotic administration of a chia phenolic extract on intestinal inflammation, intestinal barrier, brush border membrane functionality, intestinal microbiota, and morphology in vivo ( model).

Prebiotic effect of poly-D-3-hydroxybutyrate prevents dyslipidemia in obese mice.

Obesity is a global health problem caused by genetic, environmental, and psychological factors and is associated with various health disorders. As such, there is a growing focus on the prevention of obesity and related diseases. The gut microbiota plays a crucial role in these diseases and has become a therapeutic target.

Chia flour combined with a high fat diet increases propionic acid production and improves the microbial richness and diversity in female Wistar rats.

Chia is a functional food because of its positive impact on reducing the risk of metabolic diseases. These benefits are due to its nutritional composition as a source of dietary fiber and bioactive compounds. In our previous study, chia consumption increased the richness of the microbiota and the production of short chain fatty acids (SCFAs) when consumed by male Wistar rats, so, the objective of this study was to assess the effects of the consumption of chia with a high fat diet on gut health in female Wistar rats.

Preclinical in vitro evaluation of immune suppression induced by GYM329, Fc-engineered sweeping antibody.

Fc-engineering is commonly used to improve the therapeutic potency of antibody (Ab) treatments. Because FcγRIIb is the only inhibitory FcγR that contains an immunoreceptor tyrosine-based inhibition motif (ITIM), Fc-engineered Abs with enhanced binding affinity to FcγRIIb might provide immune suppression in clinical contexts. GYM329 is an anti-latent myostatin Fc-engineered Ab with increased affinity to FcγRIIb which is expected to improve muscle strength in patients with muscular disorders.

One-day systemic corticosteroid administration for asthma and future "short bursts" risk in real clinical practice.

Objective: Systemic corticosteroid administration, also called short bursts (SB), is harmful for patients with asthma; however, the actual burden of one-day SB remains unsolved. This study aimed to elucidate the characteristics of patients requiring one-day SB against asthma in clinical practice.

Methods: Consecutive patients who regularly visited our hospital for asthma treatment between January 2019 and December 2020 were reviewed and followed for one year.