Directed Evolution of a Cp*RhIII-Linked Biohybrid Catalyst Based on a Screening Platform with Affinity Purification

Directed evolution of Cp*Rh^III-linked nitrobindin (NB), a biohybrid catalyst, was performed based on an in vitro screening approach. A key aspect of this effort was the establishment of a high-throughput screening (HTS) platform that involves an affinity purification step employing a starch-agarose resin for a maltose binding protein (MBP) tag. The HTS platform enables efficient preparation of the purified MBP-tagged biohybrid catalysts in a 96-well format and eliminates background influence of the host E. coli cells. Three rounds of directed evolution and screening of more than 4000 clones yielded a Cp*Rh^III-linked NB(T98H/L100K/K127E) variant with a 4.9-fold enhanced activity for the cycloaddition of acetophenone oximes with alkynes. It is confirmed that this HTS platform for directed evolution provides an efficient strategy for generating highly active biohybrid catalysts incorporating a synthetic metal cofactor.     

Supramolecular Zn(II)-Dipicolylamine-Azobenzene-Aminocyclodextrin-ATP Complex: Design and ATP Recognition in Water

Cyclodextrins (CyDs) are water-soluble host molecules possessing a nanosized hydrophobic cavity. In the realm of molecular recognition, this cavity is used not only as a recognition site but also as a reaction medium, where a hydrophobic sensor recognizes a guest molecule. Based on the latter concept, we have designed a novel supramolecular sensing system composed of Zn(II)-dipicolylamine metal complex-based azobenzene (1-Zn) and 3A-amino-3A-deoxy-(2AS,3AS)-γ-cyclodextrin (3-NH₂-γ-CyD) for sensing adenosine-5′-triphosphate (ATP). 1-Zn showed redshifts in the UV-Vis spectra and induced circular dichroism (ICD) only when both ATP and 3-NH₂-γ-CyD were present. Calculations of equilibrium constants indicated that the amino group of 3-NH₂-γ-CyD was involved in the formation of supramolecular 1-Zn/3-NH₂-γ-CyD/ATP. The Job plot of the ICD spectral response revealed that the stoichiometry of 1-Zn/3-NH₂-γ-CyD/ATP was 2:1:1. The pH effect was examined and 1-Zn/3-NH₂-γ-CyD/ATP was most stable in the neutral condition. The NOESY spectrum suggested the localization of 1-Zn in the 3-NH₂-γ-CyD cavity. Based on the obtained results, the metal coordination interaction of 1-Zn and the electrostatic interaction of 3-NH₂-γ-CyD were found to take place for ATP recognition. The “reaction medium approach” enabled us to develop a supramolecular sensing system that undergoes multi-point interactions in water. This study is the first step in the design of a selective sensing system based on a good understanding of supramolecular structures.     

Mimic Drug Dosage Modulation for Neuroplasticity Based on Charge-Trap Layered Electronics

The human brain is often likened to an incredibly complex and intricate computer, rather than electrical devices, consisting of billions of neuronal cells connected by synapses. Different brain circuits are responsible for coordinating and performing specific functions. The reward pathway of the synaptic plasticity in the brain is strongly related to the features of both drug addiction and relief. In the current study, a synaptic device based on layered hafnium disulfide (HfS₂) is developed for the first time, to emulate the behavioral mechanisms of drug dosage modulation for neuroplasticity. A strong gate-dependent persistent photocurrent is observed, arising from the modulation of substrate-trapping events. By controlling the polarity of gate voltage, the basic functions of biological synapses are realized under a range of light spiking conditions. Furthermore, under the control of detrapping/trapping events at the HfS₂/SiO₂ interface, positive/negative correlations of the A_n/A₁ index, which significantly reflected the weight change of synaptic plasticity, are realized under the same stimulation conditions for the emulation of the drug-related addition/relief behaviors in the brain. The findings provide a new advance for mimicking human brain plasticity.     

Molecular Targeted Therapy for the Bone Loss Secondary to Pyogenic Spondylodiscitis Using Medications for Osteoporosis: A Literature Review

Pyogenic spondylodiscitis can cause severe osteolytic and destructive lesions in the spine. Elderly or immunocompromised individuals are particularly susceptible to infectious diseases; specifically, infections in the spine can impair the ability of the spine to support the trunk, causing patients to be bedridden, which can also severely affect the physical condition of patients. Although treatments for osteoporosis have been well studied, treatments for bone loss secondary to infection remain to be elucidated because they have pathological manifestations that are similar to but distinct from those of osteoporosis. Recently, we encountered a patient with severely osteolytic pyogenic spondylodiscitis who was treated with romosozumab and exhibited enhanced bone formation. Romosozumab stimulated canonical Wnt/β-catenin signaling, causing robust bone formation and the inhibition of bone resorption, which exceeded the bone loss secondary to infection. Bone loss due to infections involves the suppression of osteoblastogenesis by osteoblast apoptosis, which is induced by the nuclear factor-κB and mitogen-activated protein kinase pathways, and osteoclastogenesis with the receptor activator of the nuclear factor-κB ligand-receptor combination and subsequent activation of the nuclear factor of activated T cells cytoplasmic 1 and c-Fos. In this study, we review and discuss the molecular mechanisms of bone loss secondary to infection and analyze the efficacy of the medications for osteoporosis, focusing on romosozumab, teriparatide, denosumab, and bisphosphonates, in treating this pathological condition.     

Feasibility of zeolites in converting butyric acid into propylene for biorefineries

The biorefinery has been recognized as a new industry to produce both energy and chemical materials such as olefins and BTX from renewable resources. In this context the conversion of butyric acid over zeolites was investigated for establishing a new production route of propylene. Propylene was mainly generated by decarbonylation and dehydration of butyric acid. Our study proved that H-ZSM-5 (750) and silicalite were the best industrial catalyst among the tested ones. For H-ZSM-5 (750), the selectivity of propylene reached 64.2 C% and the ratio of the yield for propylene to theoretical yield (75 C%) became 85.6%.     

Quantification of the Phase Transformation Kinetics in High Chromium Cast Irons Using Dilatometry and Metallographic Techniques

Metallurgical and Materials Transactions A - Further development of high chromium cast irons (HCCI) is based on tailoring the microstructure, necessitating an accurate control over the phase...     

Simulation of producer gas flameless combustion with fresh reactant diluted by hot flue gas

Flameless combustion is considered as a flexible and efficient combustion process for low heating value gas fuel. This paper presents numerical simulations of premixed flameless combustion using producer gas as a fuel. Different initial conditions of the premixed fresh reactant (air/fuel mixture) and dilution levels are taken into account for the investigation. The numerical simulations were investigated using a network of chemical reactor models with the detailed reaction mechanism of GRI‐Mech 3.0. A threshold dilution level for flameless combustion fuelled by producer gas was determined. The numerical results show that dilution of the fresh reactant with hot combustion products and initial fresh reactant temperature play important roles in flameless combustion formation and its auto‐ignition behaviour, rather than equivalence ratio of the fresh reactant. In the flameless combustion regime, temperature and chemical concentrations were reduced while chemical kinetics process was decelerated, resulting in delay of the auto‐ignition process.     

Pregnancy by Assisted Reproductive Technology Is Associated with Shorter Telomere Length in Neonates

Telomere length (TL) influences the development of lifestyle-related diseases, and neonatal TL may influence their prevalence. Various factors have been reported to affect neonatal TL. Although the fetus is exposed to multiple conditions in utero, the main factors affecting the shortening of neonatal TL are still not known. In this study, we sought to identify factors that influence fetal TL. A total of 578 mother-newborn pairs were included for TL analysis. TL was measured in genomic DNA extracted from cord blood samples using quantitative PCR. The clinical factors examined at enrollment included the following intrauterine environmental factors: maternal age, assisted reproductive technology (ART) used, body mass index (BMI), gestational diabetes mellitus (GDM), maternal stress, smoking, alcohol consumption, preterm delivery, small-for-gestational-age, neonatal sex, and placental weight. Univariate and multivariate regression analyses were used to verify the relationship between neonatal TL and these clinical factors. The median neonatal TL to single-copy gene ratio was 1.0. Pregnancy with ART was among the 11 factors associated with shorter neonatal TL. From multiple regression analysis, we determined that neonatal TL was significantly shorter for pregnancies in the ART group than in the other groups. We conclude that pregnancy with ART is associated with shorter neonatal TL.