MOF-Derived Cu@Cu2O Nanocatalyst for Oxygen Reduction Reaction and Cycloaddition Reaction

Research on the synthesis of nanomaterials using metal-organic frameworks (MOFs), which are characterized by multi-functionality and porosity, as precursors have been accomplished through various synthetic approaches. In this study, copper and copper oxide nanoparticles were fabricated within 30 min by a simple and rapid method involving the reduction of a copper(II)-containing MOF with sodium borohydride solution at room temperature. The obtained nanoparticles consist of a copper core and a copper oxide shell exhibited catalytic activity in the oxygen reduction reaction. The as-synthesized Cu@Cu2O core-shell nanocatalyst exhibited an enhanced limit current density as well as onset potential in the electrocatalytic oxygen reduction reaction (ORR). Moreover, the nanoparticles exhibited good catalytic activity in the Huisgen cycloaddition of various substituted azides and alkynes under mild reaction conditions

Advancing Patient Care: Innovative Use of Near-Infrared Spectroscopy for Monitoring Urine Volume in Neurogenic Bladder

Purpose Current guidelines recommend clean intermittent catheterization (CIC) at regular time intervals for patients with spinal cord injuries; however, many patients experience difficulties. Performing time-based CIC outside the home is a significant burden for patients. In this study, we aimed to overcome the limitations of the current guidelines by developing a digital device to monitor bladder urine volume in real-time. Methods The optode sensor is a near-infrared spectroscopy (NIRS)-based wearable device intended to be attached to the skin of the lower abdomen where the bladder is located. The sensor’s primary function is to detect changes in urine volume within the bladder. An in vitro study was conducted using a bladder phantom that mimicked the optical properties of the lower abdomen. To validate the data in the human body at the proof-of-concept level, one volunteer attached the device to the lower abdomen to measure the light intensity between the first voiding and immediately before the second voiding. Results The degree of attenuation at the maximum test volume was equivalent across experiments, and the optode sensor with multiplex measurements demonstrated robust performance for patient diversity. Moreover, the symmetric feature of the matrix was deemed a potential parameter for identifying the accuracy of sensor localization in a deep-learning model. The validated feasibility of the sensor showed almost the same results as an ultrasound scanner, which is routinely used in the clinical field. Conclusions The optode sensor of the NIRS-based wearable device can measure the urine volume in the bladder in real-time

Intracellular Nanomaterial Delivery via Spiral Hydroporation

In recent nanobiotechnology developments, a wide variety of functional nanomaterials and engineered biomolecules have been created, and these have numerous applications in cell biology. For these nanomaterials to fulfill their promises completely, they must be able to reach their biological targets at the subcellular level and with a high level of specificity. Traditionally, either nanocarrier- or membrane disruption-based method has been used to deliver nanomaterials inside cells; however, these methods are suboptimal due to their toxicity, inconsistent delivery, and low throughput, and they are also labor intensive and time-consuming, highlighting the need for development of a next-generation, intracellular delivery system. This study reports on the development of an intracellular nanomaterial delivery platform, based on unexpected cell-deformation phenomena via spiral vortex and vortex breakdown exerted in the cross- and T-junctions at moderate Reynolds numbers. These vortex-induced cell deformation and sequential restoration processes open cell membranes transiently, allowing effective and robust intracellular delivery of nanomaterials in a single step without the aid of carriers or external apparatus. By using the platform described here (termed spiral hydroporator), we demonstrate the delivery of different nanomaterials, including gold nanoparticles (200 nm diameter), functional mesoporous silica nanoparticles (150 nm diameter), dextran (hydrodynamic diameters between 2–55 nm), and mRNA, into different cell types. We demonstrate here that the system is highly efficient (up to 96.5%) with high throughput (up to 1 × 106 cells/min) and rapid delivery (∼1 min) while maintaining high levels of cell viability (up to 94%)

Azide-Alkyne Huisgen [3+2] Cycloaddition Using CuO Nanoparticles

Recent developments in the synthesis of CuO nanoparticles (NPs) and their application to the [3+2] cycloaddition of azides with terminal alkynes are reviewed. With respect to the importance of click chemistry, CuO hollow NPs, CuO hollow NPs on acetylene black, water-soluble double-hydrophilic block copolymer (DHBC) nanoreactors and ZnO-CuO hybrid NPs were synthesized. Non-conventional energy sources such as microwaves and ultrasound were also applied to these click reactions, and good catalytic activity with high regioselectivity was observed. CuO hollow NPs on acetylene black can be recycled nine times without any loss of activity, and water-soluble DHBC nanoreactors have been developed for an environmentally friendly process.open6

Depression and suicide risk prediction models using blood-derived multi-omics data

More than 300 million people worldwide experience depression; annually, ~800,000 people die by suicide. Unfortunately, conventional interview-based diagnosis is insufficient to accurately predict a psychiatric status. We developed machine learning models to predict depression and suicide risk using blood methylome and transcriptome data from 56 suicide attempters (SAs), 39 patients with major depressive disorder (MDD), and 87 healthy controls. Our random forest classifiers showed accuracies of 92.6% in distinguishing SAs from MDD patients, 87.3% in distinguishing MDD patients from controls, and 86.7% in distinguishing SAs from controls. We also developed regression models for predicting psychiatric scales with R2 values of 0.961 and 0.943 for Hamilton Rating Scale for Depression???17 and Scale for Suicide Ideation, respectively. Multi-omics data were used to construct psychiatric status prediction models for improved mental health treatment

High-throughput enzyme screening platform for the IPP-bypass mevalonate pathway for isopentenol production

Isopentenol (or isoprenol, 3-methyl-3-buten-1-ol) is a drop-in biofuel and a precursor for commodity chemicals such as isoprene. Biological production of isopentenol via the mevalonate pathway has been optimized extensively in Escherichia coli, yielding 70% of its theoretical maximum. However, high ATP requirements and isopentenyl diphosphate (IPP) toxicity pose immediate challenges for engineering bacterial strains to overproduce commodities utilizing IPP as an intermediate. To overcome these limitations, we developed an "IPP-bypass" isopentenol pathway using the promiscuous activity of a mevalonate diphosphate decarboxylase (PMD) and demonstrated improved performance under aeration-limited conditions. However, relatively low activity of PMD toward the non-native substrate (mevalonate monophosphate, MVAP) was shown to limit flux through this new pathway. By inhibiting all IPP production from the endogenous non-mevalonate pathway, we developed a high-throughput screening platform that correlated promiscuous PMD activity toward MVAP with cellular growth. Successful identification of mutants that altered PMD activity demonstrated the sensitivity and specificity of the screening platform. Strains with evolved PMD mutants and the novel IPP-bypass pathway increased titers up to 2.4-fold. Further enzymatic characterization of the evolved PMD variants suggested that higher isopentenol titers could be achieved either by altering residues directly interacting with substrate and cofactor or by altering residues on nearby α-helices. These altered residues could facilitate the production of isopentenol by tuning either kcat or Ki of PMD for the non-native substrate. The synergistic modification made on PMD for the IPP-bypass mevalonate pathway is expected to significantly facilitate the industrial scale production of isopentenol

Optimization of the IPP-bypass mevalonate pathway and fed-batch fermentation for the production of isoprenol in Escherichia coli.

Isoprenol (3-methyl-3-buten-1-ol) is a drop-in biofuel and a precursor for commodity chemicals. Biological production of isoprenol via the mevalonate pathway has been developed and optimized extensively in Escherichia coli, but high ATP requirements and isopentenyl diphosphate (IPP) toxicity have made it difficult to achieve high titer, yield, and large-scale production. To overcome these limitations, an IPP-bypass pathway was previously developed using the promiscuous activity of diphosphomevalonate decarboxylase, and enabled the production of isoprenol at a comparable yield and titer to the original pathway. In this study, we optimized this pathway, substantially improving isoprenol production. A titer of 3.7 g/L (0.14 g isoprenol per g glucose) was achieved in batch conditions using minimal medium by pathway optimization, and a further optimization of the fed-batch fermentation process enabled an isoprenol titer of 10.8 g/L (yield of 0.105 g/g and maximum productivity of 0.157 g L-1 h-1), which is the highest reported titer for this compound. The substantial increase in isoprenol titer via the IPP-bypass pathway in this study will facilitate progress toward commercialization

Isopentenyl diphosphate (IPP)-bypass mevalonate pathways for isopentenol production

a b s t r a c t Branched C 5 alcohols are promising biofuels with favorable combustion properties. A mevalonate (MVA)-based isoprenoid biosynthetic pathway for C 5 alcohols was constructed in Escherichia coli using genes from several organisms, and the pathway was optimized to achieve over 50% theoretical yield. Although the MVA pathway is energetically less efficient than the native methylerythritol 4-phosphate (MEP) pathway, implementing the MVA pathway in bacterial hosts such as E. coli is advantageous due to its lack of endogenous regulation. The MVA and MEP pathways intersect at isopentenyl diphosphate (IPP), the direct precursor to isoprenoid-derived C 5 alcohols and initial precursor to longer chain terpenes, which makes independent regulation of the pathways difficult. In pursuit of the complete "decoupling" of the MVA pathway from native cellular regulation, we designed novel IPP-bypass MVA pathways for C 5 alcohol production by utilizing promiscuous activities of two enzymes, phosphomevalonate decarboxylase (PMD) and an E. coli-endogenous phosphatase (AphA). These bypass pathways have reduced energetic requirements, are further decoupled from intrinsic regulation, and are free from IPP-related toxicity. In addition to these benefits, we demonstrate that reduced aeration rate has less impact on the bypass pathway than the original MVA pathway. Finally, we showed that performance of the bypass pathway was primarily determined by the activity of PMD. We designed PMD mutants with improved activity and demonstrated titer increases in the mutant strains. These modified pathways would be a good platform for industrial production of isopentenol and related chemicals such as isoprene