Identification of stable reference genes for relative quantification of long RNA expression in urinary extracellular vesicles.

Urinary extracellular vesicles (uEVs) are rich in valuable biomolecule information which are increasingly recognized as potential biomarkers for various diseases. uEV long RNAs are among the critical cargos capable of providing unique transcriptome information of the source cells. However, consensus regarding ideal reference genes for relative long RNAs quantification in uEVs is not available as of date.

Safety, pharmacokinetics, and food-effect of pivmecillinam after single- and multiple-dose in healthy Chinese subjects: a phase I study.

Urinary tract infection (UTI) is one of the most prevalent bacterial infectious diseases worldwide. However, the resistance of urinary pathogens to other UTI antibiotics such as trimethoprim and trimethoprim/sulphamethoxazole increased. Pivmecillinam is a prodrug of mecillinam, which is effective for the treatment of urinary tract infections.

Measurement of urinary exosomal phospholipase A2 receptor is a sensitive method for diagnosis of PLA2R-associated membranous nephropathy.

Background: The discovery of phospholipase A2 receptor (PLA2R) and its antibody (aPLA2Rab) has paved the way for diagnosing PLA2R-associated membranous nephropathy (PLA2R-MN) with a high specificity of 98%. However, the sensitivity was only 40% to 83.9%, and there is ongoing discussion around determining the optimal threshold for diagnosis.

The sulfate assimilation and reduction of marine microalgae and the regulation of illumination.

To examine the sulfate assimilation and reduction process and the regulation of illumination, diatom Phaeodactylum tricornutum and dinoflagellate Amphidinium carterae were selected for continuous simulation incubation under different photon flux densities (PFDs) (54, 108 and 162 μmol photons m s), and concentration variations of related sulfur compounds sulfate, dimethylsulfoniopropionate (DMSP), dimethylsulfide (DMS) and acrylic acid (AA) in the culture system were observed. The optimal PFD for the growth of two microalgae was 108 μmol photons m s. However, the maximum sulfate absorption occurred at 162 μmol photons m s for P.

Photo-Facilitated Detection and Sequencing of 5-Formylcytidine RNA.

5-Formylcytidine (f C) is one of the epigenetic nucleotides in tRNA. Despite the evident importance of f C in gene expression regulation, little is known about its exact amount and position. To capture this information, we developed a modification-specific functionalization with a semi-stabilized ylide.

A Light-Controllable Chemical Modulation of m A RNA Methylation.

Bioactive small molecules with photo-removable protecting groups have provided spatial and temporal control of corresponding biological effects. We present the design, synthesis, computational and experimental evaluation of the first photo-activatable small-molecule methyltransferase agonist. By blocking the functional N-H group on MPCH with a photo-removable ortho-nitrobenzyl moiety, we have developed a promising photo-caged compound that had completely concealed its biological activity.

Mutational Analysis of a Familial Adenomatous Polyposis Pedigree with Bile Duct Polyp Phenotype.

A large number of colorectal cancers have a genetic background in China. However, due to insufficient awareness, the diagnostic rate remains low and merely 5-6% of colorectal cancer patients are diagnosed with hereditary colorectal cancer. Familial adenomatous polyposis (FAP) is an autosomal dominant genetic disease caused by mutations in the adenomatous polyposis coli (APC) gene.

Pharmacogenetic and safety analysis of cinacalcet hydrochloride in healthy Chinese subjects.

Background: Our study aims to explore the effect of genetics on the pharmacodynamics (PD) and pharmacokinetics (PK) of cinacalcet in healthy Chinese subjects; to investigate the effect of dietary factors on cinacalcet, and to evaluate the safety of cinacalcet under fasting and non-fasting conditions using a bioequivalence trial.

Methods: We investigated the relationship of cinacalcet PK with single nucleotide polymorphisms (SNPs) of CYP3A4, CYP1A2 and CYP2D6, and of cinacalcet PD with SNPs of calcium-sensitive receptors (CASR) and vitamin D receptors (VDR) in 65 healthy Chinese subjects recruited to participate in this study. Our study was a phase I, open-label, randomized, two-period, two-sequence crossover, a single-center clinical study designed under both fasting and non-fasting conditions to investigate the effect of dietary factors on cinacalcet.

Tolerability, Safety, Pharmacokinetics and Drug Interaction of Cefotaxime Sodium-Tazobactam Sodium Injection (6:1) Following Single and Multiple Intravenous Doses in Chinese Healthy Subjects.

Purpose: To evaluate the tolerability, safety, pharmacokinetics and drug interaction of cefotaxime sodium-tazobactam sodium injection (6:1) in Chinese healthy subjects. The results of the safety and pharmacokinetic studies supported further clinical trials.

Method: A randomized, single-blind, ascending dose, placebo-controlled, single-center study was conducted.

Effects of ABCB1, UGT1A1, and UGT1A9 Genetic Polymorphisms on the Pharmacokinetics of Sitafloxacin Granules in Healthy Subjects.

Sitafloxacin, a new fluoroquinolone, has strong antibacterial activity. We evaluated the effects of sitafloxacin granules in single-dose and multidose cohorts and the effects of ABCB1, UGT1A1, and UGT1A9 genetic polymorphisms on the pharmacokinetics (PK) of sitafloxacin in healthy subjects. The single-dose study included 3 fasted cohorts receiving 50, 100, and 200 mg of sitafloxacin granules and 1 cohort receiving 50 mg of sitafloxacin granules with a high-fat meal.

Chemical Deprenylation of N -Isopentenyladenosine (i A) RNA.

N -isopentenyladenosine (i A) is an RNA modification found in cytokinins, which regulate plant growth/differentiation, and a subset of tRNAs, where it improves the efficiency and accuracy of translation. The installation and removal of this modification is mediated by prenyltransferases and cytokinin oxidases, and a chemical approach to selective deprenylation of i A has not been developed. We show that a selected group of oxoammonium cations function as artificial deprenylases to promote highly selective deprenylation of i A in nucleosides, oligonucleotides, and live cells.

Effects of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of proton pump inhibitors.

Proton pump inhibitors (PPIs) are used widely for the treatment of acid-related disorders. Despite their excellent efficacy and tolerance, the pharmacodynamics and pharmacokinetics of PPIs are affected by each patient's CYP2C19 and gastric H,K-ATPase genotype. The aim of this review was to analyze the effect of genetic polymorphisms on the pharmacodynamic and pharmacokinetic properties of PPIs.

Modifying Methionine on Proteins.

Methionine has been recognized as an ideal target for labeling proteins without disturbing their tasks. However, exploration in single post-transcriptional modification of methionine is sluggish. In this Highlight, we summarize some of the most exciting reports on the precise control of protein function by selectively modifying methionine residues.

Selective Inhibitors of AlkB Family of Nucleic Acid Demethylases.

The α-ketoglutarate-dependent (AlkB) superfamily of Fe/2-oxoglutarate (2-OG)-dependent dioxygenases consists of a unique class of nucleic acid repair enzymes that reversibly remove alkyl substituents from nucleobases through oxidative dealkylation. Recent studies have verified the involvement of AlkB dioxygenases in a variety of human diseases. However, the development of small organic molecules that can function as enzyme inhibitors to block the action of oxidative dealkylation is still in its infancy.

Identification of Flavin Mononucleotide as a Cell-Active Artificial N -Methyladenosine RNA Demethylase.

N -Methyladenosine (m A) represents a common and highly dynamic modification in eukaryotic RNA that affects various cellular pathways. Natural dioxygenases such as FTO and ALKBH5 are enzymes that demethylate m A residues in mRNA. Herein, the first identification of a small-molecule modulator that functions as an artificial m A demethylase is reported.

HLA class II alleles differing by a single amino acid associate with clinical phenotype and outcome in patients with primary membranous nephropathy.

Genome-wide associations and HLA genotyping have revealed associations between HLA alleles and susceptibility to primary membranous nephropathy. However, associations with clinical phenotypes and kidney outcome are poorly defined. We previously identified DRB1*1501 and DRB1*0301 as independent risk alleles for primary membranous nephropathy.

Ruthenium-Catalyzed Decarboxylative C-H Alkenylation in Aqueous Media: Synthesis of Tetrahydropyridoindoles.

We disclose herein a Ru(II)-catalyzed decarboxylative and oxidative coupling of N-substituted indolyl carboxylic acids with broad substrate scope in an aqueous solution. This method provides a sustainable and efficient access to synthesize various indole-fused cyclohexanyl acetic acids under mild conditions.

Impact of Gastric rs2733743 on the Intragastric pH-Values of Dexlansoprazole Injection in Chinese Subjects.

Not all patients with acid-related disorders receiving proton pump inhibitor (PP) treatment get adequate gastric pH control. The genetic variation of receptors, metabolic enzymes, and transporters are known to cause failures of therapies. We have conducted a study to evaluate the influence of gastric , and polymorphisms on the pharmacokinetic and pharmacodynamic profiles of dexlansoprazole injection in healthy Chinese subjects.

Visible-light-mediated oxidative demethylation of N-methyl adenines.

We report a simple protocol that affords oxidative demethylation of N-methyl groups in N-methyl adenines (mA). The biologically compatible photocatalyst riboflavin prompts a highly selective C-H abstraction from N-methyl in adenines under the irradiation of a visible blue LED light, affording a novel and highly selective biomimetic demethylation of mA and related N-methyl adenine analogues.

The susceptible HLA class II alleles and their presenting epitope(s) in Goodpasture's disease.

Goodpasture's disease is closely associated with HLA, particularly DRB1*1501. Other susceptible or protective HLA alleles are not clearly elucidated. The presentation models of epitopes by susceptible HLA alleles are also unclear.

Fever and prodromal infections in anti-glomerular basement membrane disease.

Aim: Anti-glomerular basement membrane (GBM) disease is an autoimmune disorder with rapidly progressive glomerulonephritis and alveolar haemorrhage. Fever symptoms and prodromal infections have been reported in many cases, but still not been elucidated.

Methods: Our study enrolled 140 consecutive patients with anti-GBM disease and retrospectively analyzed the characteristics of fever symptoms and the possible reasons.