3D Crystal Construction by Single-Crystal 2D Material Supercell Multiplying.

2D stacking presents a promising avenue for creating periodic superstructures that unveil novel physical phenomena. While extensive research has focused on lateral 2D material superstructures formed through composition modulation and twisted moiré structures, the exploration of vertical periodicity in 2D material superstructures remains limited. Although weak van der Waals interfaces enable layer-by-layer vertical stacking, traditional methods struggle to control in-plane crystal orientation over large areas, and the vertical dimension is constrained by unscalable, low-throughput processes, preventing the achievement of global order structures.

Engineered Imine Reductase Catalyzed Enantiodivergent Synthesis of Alkylated Amphetamines.

Less steric ketones exhibited low stereoselectivity toward M5 due to their difficulty in restricting the free rotation of the imine intermediate. An engineered enantio-complementary imine reductase from M5 was obtained with catalytic activity. We identified four key residues that play essential roles in controlling stereoselectivity.

Synthetic Nicotinamide Cofactors as Alternatives to NADPH in Imine Reductase-Catalyzed Reactions.

This study demonstrates the effectiveness of synthetic nicotinamide cofactors as cost-effective alternatives to NADPH in imine reductase (IRED) catalysis. The synthetic cofactors maintained catalytic activity and stereoselectivity, achieving high conversion rates. Molecular docking studies revealed key structural interactions influencing performance.

Microbial signatures predictive of short-term prognosis in severe pneumonia.

Objective: This retrospective cohort study aimed to investigate the composition and diversity of lung microbiota in patients with severe pneumonia and explore its association with short-term prognosis.

Methods: A total of 301 patients diagnosed with severe pneumonia underwent bronchoalveolar lavage fluid metagenomic next-generation sequencing (mNGS) testing from February 2022 to January 2024. After applying exclusion criteria, 236 patients were included in the study.

Cell-free DNA methylation patterns in aging and their association with inflamm-aging.

Liquid biopsies analyzing cell-free DNA (cfDNA) methylation in plasma offer a noninvasive diagnostic for diseases, with the potential of aging biomarkers underexplored. Utilizing enzymatic methyl-seq (EM-seq), this study assessed cfDNA methylation patterns in aging with blood from 35 healthy individuals. It found aging signatures, including higher cfDNA levels and variations in fragment sizes, plus approximately 2000 age-related differentially methylated CpG sites.

Chemoenzymatic total synthesis of rotigotine IRED-catalyzed reductive amination.

A short and chemoenzymatic synthesis of rotigotine using an IR-36-M5 mutant is reported. Focusing on the residues that directly contact the 2-tetralone moiety, we applied structure-guided semi-rational design to obtain a double-mutant F260W/M147Y, which showed a good isolated yield and -stereoselectivity >99% toward 2-aminotetralin synthesis. Furthermore, the utility of this biocatalytic protocol was successfully demonstrated in the enantioselective synthesis of rotigotine enzymatic reductive amination as the key step.

Semi-rational design of an imine reductase for asymmetric synthesis of alkylated -4-azepanamines.

Although imine reductase (IRED)-catalyzed reductive amination is promising for the synthesis of alkylated chiral amines, precisely regulating the stereoselectivity of IRED remains a great challenge. Herein, focusing on the residues directly in contact with the ketone moiety, we applied structure-guided semi-rational design to obtain the triple-mutant I149Y/L200H/W234K. This mutant showed high stereoselectivity, of up to >99% (), toward reductive amination of -Boc-4-oxo-azepane and different amines, and to the best of our knowledge is the first biocatalyst developed for asymmetric synthesis of chiral azepane-4-amines.

Actinomycetes-derived imine reductases with a preference towards bulky amine substrates.

Since imine reductases (IREDs) were reported to catalyze the reductive amination reactions, they became particularly attractive for producing chiral amines. Though diverse ketones and aldehydes have been proved to be excellent substrates of IREDs, bulky amines have been rarely transformed. Here we report the usage of an Increasing-Molecule-Volume-Screening to identify a group of IREDs (IR-G02, 21, and 35) competent for accepting bulky amine substrates.

Urinary 8-oxoGuo as a potential novel evaluation index for patients with nephrotic syndrome.

Urinary 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2'- deoxyguanosine (8-oxodGuo) are considered biomarkers of oxidative stress, and patients with nephrotic syndrome have been reported to have increased oxidative stress levels. In this study, we aimed to assess the value of 8-oxoGuo and 8-oxodGuo as novel biomarkers to evaluate the severity of nephrotic syndrome. In total, 107 patients with nephrotic syndrome and 116 healthy controls were recruited for this study.

A hybrid system for the overproduction of complex ergot alkaloid chanoclavine.

Synthetic biology-based methods (Sbio) and chemical synthesis (Csyn) are two independent approaches that are both widely used for synthesizing biomolecules. In the current study, two systems were combined for the overproduction of chanoclavine (CC), a structurally complex ergot alkaloid. The whole synthetic pathway for CC was split into three sections: enzymatic synthesis of 4-Br-Trp (4-Bromo-trptophan) using cell-lysate catalysis (CLC), chemical synthesis of prechanoclavine (PCC) from 4-Br-Trp, and overproduction CC from PCC using a whole-cell catalysis (WCC) platform.

Plasma Angiopoietin-2 as a Promising Biomarker for the Prognosis of Acute Pulmonary Embolism.

Background: Endothelial damage is one of the pathogenic conditions of acute pulmonary embolism (APE). The essential role of angiogenin, ribonuclease A family, member 2 (Ang-2) in APE remains unclear. This study aimed to investigate the predictive value of Ang-2 in the clinical outcomes of patients with APE.

Tuning an Imine Reductase for the Asymmetric Synthesis of Azacycloalkylamines by Concise Structure-Guided Engineering.

Although imine reductases (IREDs) are emerging as attractive reductive aminases (RedAms), their substrate scope is still narrow, and rational engineering is rare. Focusing on hydrogen bond reorganization and cavity expansion, a concise strategy combining rational cavity design, combinatorial active-site saturation test (CAST), and thermostability engineering was designed, that transformed the weakly active IR-G36 into a variant M5 with superior performance for the synthesis of (R)-3-benzylamino-1-Boc-piperidine, with a 4193-fold improvement in catalytic efficiency, a 16.2 °C improvement in T , and a significant increase in the e.

Effects of 31 recombinant CYP2C19 variants on clomipramine metabolism in vitro.

Background: CYP2C19 is an important member of the cytochrome P450 enzyme superfamily. We recently identified 31CYP2C19 alleles in the Han Chinese population; studying the effects of CYP2C19 on drug metabolism can help reduce adverse drug reactions and therapeutic failure.

Aim: The aim of this study was to assess the catalytic activities of 31 allelic isoforms and their effects on the metabolism of clomipramine in vitro.

Effects of 27 CYP3A4 protein variants on saxagliptin metabolism in vitro.

Saxagliptin is a dipeptidyl peptidase 4 (DPP-4) inhibitor widely used in patients with type 2 diabetes. It can increase the amount of insulin after meals and lower blood sugar. CYP450 3A4 (CYP3A4) can metabolize about 30%-40% of therapeutic drugs.

Identification and Enzymatic Activity Evaluation of a Novel Allelic Variant Discovered in a Patient.

Warfarin is a widely prescribed anticoagulant but the doses required to attain the optimum therapeutic effect exhibit dramatic inter-individual variability. Pharmacogenomics-guided warfarin dosing has been recommended to improve safety and effectiveness. We analyzed the cytochrome P450 2C9 () and vitamin K epoxide reductase complex subunit 1 () genes among 120 patients taking warfarin.

Systemic RNA oxidation can be used as a biomarker of infection in challenged with .

More and more evidence support the concept that RNA oxidation plays a substantial role in the progress of multiple diseases; however, only a few studies have reported RNA oxidation caused by microbial pathogens. Urinary 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGsn), which are broadly used as indicators of oxidative damage of RNA and DNA, were analyzed in this study to determine which can be used as a biomarker of infection in challenged with (). In this work, 24 specific-pathogen-free (SPF) male SD rats were randomly divided into two groups: an infection group and a phosphate-buffered saline (PBS) control group.

Targeted elimination of intracellular reactive oxygen species using nanoparticle-like chitosan- superoxide dismutase conjugate for treatment of monoiodoacetate-induced osteoarthritis.

In our previous work, cationic functionalized chitosan was chemically conjugated with superoxide dismutase (SOD) to yield a unique nanoparticle-like conjugate O-HTCC-SOD that has demonstrated superior potential in treating reactive oxygen species (ROS)-related disorders to SOD. Considering contribution of ROS to pathogenesis of osteoarthritis, O-HTCC-SOD was firstly measured for effect on rat chondrocytes exposure to monoiodoacetate (MIA). O-HTCC-SOD was nontoxic to chondrocytes and had more long-acting and intracellular protection effects on chondrocytes against MIA-induced oxidative damage due to its superior elimination of intracellular ROS to SOD.

Efficacy and safety of levosimendan in patients with acute right heart failure: A meta-analysis.

Aims: Right heart failure (RHF), which is caused by a variety of heart and lung diseases, has a high morbidity and mortality rate. Levosimendan is a cardiac inotropic drug and vasodilator. The effect of levosimendan on RHF remains unclear.

MiR-557 works as a tumor suppressor in human lung cancers by negatively regulating LEF1 expression.

MicroRNAs play an important role in regulating post-transcriptional gene expression in the progression of various human cancers. In this study, we investigated the role of microRNA-557 in human lung cancer cells. The molecular mechanism of microRNA-557 was also clarified in the proliferation and invasion of human lung cancer cells.

The values of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in predicting 30 day mortality in patients with acute pulmonary embolism.

Background: vAcute pulmonary embolism (PE) is a life threatening disease. The treatment options depend on the severity of the disease and the mortality varies widely depending on the severity of the condition. It is important to identify patients who are at high risk of mortality.