Functional Lignin Building Blocks: Reactive Vinyl Esters with Acrylic Acid.

Introducing vinyl groups onto the backbone of technical lignin provides an opportunity to create highly reactive renewable polymers suitable for radical polymerization. In this work, the chemical modification of softwood kraft lignin was pursued with etherification, followed by direct esterification with acrylic acid (AA). In the first step, phenolic hydroxyl and carboxylic acid groups were derivatized into aliphatic hydroxyl groups using ethylene carbonate and an alkaline catalyst. The lignin was subsequently fractionated using a downward precipitation method to recover lignin of defined molar mass and solubility. After recovery, the resulting material was then esterified with AA, resulting in lignin with vinyl functional groups. The first step resulted in approximately 90% of phenolic hydroxyl groups being converted into aliphatic hydroxyls, while the downward fractionation resulted in three samples of lignin with defined molar masses. For the esterification reaction, the weight ratio of reagents, reaction temperature, and reaction time were evaluated as factors that would influence the modification efficacy. 13C NMR spectroscopy analysis of lignin samples before and after esterification showed that the optimized reaction conditions could reach approximately 40% substitution of aliphatic hydroxyl groups. Both steps only used lignin and the modifying reagent (no solvent), with the possibility of recovery and reuse of the reagent by dilution and distillation. An additional second esterification step of the resulting lignin sample with acetic acid or propionic acid converted 90% of remaining hydroxyl groups into short-chain carbon aliphatic esters, making a hydrophobic material suitable for further copolymerization with synthetic hydrophobic monomers.

One-Pot, One-Step Synthesis of Drug-Loaded Magnetic Multimicelle Aggregates.

Lipid-based formulations provide a nanotechnology platform that is widely used in a variety of biomedical applications because it has several advantageous properties including biocompatibility, reduced toxicity, relative ease of surface modifications, and the possibility for efficient loading of drugs, biologics, and nanoparticles. A combination of lipid-based formulations with magnetic nanoparticles such as iron oxide was shown to be highly advantageous in a growing number of applications including magnet-mediated drug delivery and image-guided therapy. Currently, lipid-based formulations are prepared by multistep protocols. Simplification of the current multistep procedures can lead to a number of important technological advantages including significantly decreased processing time, higher reaction yield, better product reproducibility, and improved quality. Here, we introduce a one-pot, single-step synthesis of drug-loaded magnetic multimicelle aggregates (MaMAs), which is based on controlled flow infusion of an iron oxide nanoparticle/lipid mixture into an aqueous drug solution under ultrasonication. Furthermore, we prepared molecular-targeted MaMAs by directional antibody conjugation through an Fc moiety using Cu-free click chemistry. Fluorescence imaging and quantification confirmed that antibody-conjugated MaMAs showed high cell-specific targeting that was enhanced by magnetic delivery.

Integration of renewable deep eutectic solvents with engineered biomass to achieve a closed-loop biorefinery.

Despite the enormous potential shown by recent biorefineries, the current bioeconomy still encounters multifaceted challenges. To develop a sustainable biorefinery in the future, multidisciplinary research will be essential to tackle technical difficulties. Herein, we leveraged a known plant genetic engineering approach that results in aldehyde-rich lignin via down-regulation of cinnamyl alcohol dehydrogenase (CAD) and disruption of monolignol biosynthesis. We also report on renewable deep eutectic solvents (DESs) synthesized from phenolic aldehydes that can be obtained from CAD mutant biomass. The transgenic Arabidopsis thaliana CAD mutant was pretreated with the DESs and showed a twofold increase in the yield of fermentable sugars compared with wild type (WT) upon enzymatic saccharification. Integrated use of low-recalcitrance engineered biomass, characterized by its aldehyde-type lignin subunits, in combination with a DES-based pretreatment, was found to be an effective approach for producing a high yield of sugars typically used for cellulosic biofuels and biobased chemicals. This study demonstrates that integration of renewable DES with plant genetic engineering is a promising strategy in developing a closed-loop process.

Unsupervised Domain Adaptive 1D-CNN for Fault Diagnosis of Bearing.

Fault diagnosis (FD) plays a vital role in building a smart factory regarding system reliability improvement and cost reduction. Recent deep learning-based methods have been applied for FD and have obtained excellent performance. However, most of them require sufficient historical labeled data to train the model which is difficult and sometimes not available. Moreover, the big size model increases the difficulties for real-time FD. Therefore, this article proposed a domain adaptive and lightweight framework for FD based on a one-dimension convolutional neural network (1D-CNN). Particularly, 1D-CNN is designed with a structure of autoencoder to extract the rich, robust hidden features with less noise from source and target data. The extracted features are processed by correlation alignment (CORAL) to minimize domain shifts. Thus, the proposed method could learn robust and domain-invariance features from raw signals without any historical labeled target domain data for FD. We designed, trained, and tested the proposed method on CRWU bearing data sets. The sufficient comparative analysis confirmed its effectiveness for FD.

A deep learning model based on concatenation approach to predict the time to extract a mandibular third molar tooth.

BACKGROUND: Assessing the time required for tooth extraction is the most important factor to consider before surgeries. The purpose of this study was to create a practical predictive model for assessing the time to extract the mandibular third molar tooth using deep learning. The accuracy of the model was evaluated by comparing the extraction time predicted by deep learning with the actual time required for extraction. METHODS: A total of 724 panoramic X-ray images and clinical data were used for artificial intelligence (AI) prediction of extraction time. Clinical data such as age, sex, maximum mouth opening, body weight, height, the time from the start of incision to the start of suture, and surgeon's experience were recorded. Data augmentation and weight balancing were used to improve learning abilities of AI models. Extraction time predicted by the concatenated AI model was compared with the actual extraction time. RESULTS: The final combined model (CNN + MLP) model achieved an R value of 0.8315, an R-squared value of 0.6839, a p-value of less than 0.0001, and a mean absolute error (MAE) of 2.95 min with the test dataset. CONCLUSIONS: Our proposed model for predicting time to extract the mandibular third molar tooth performs well with a high accuracy in clinical practice.

Genome-wide identification and characterization of NBS-encoding genes in Raphanus sativus L. and their roles related to Fusarium oxysporum resistance.

BACKGROUND: The nucleotide-binding site-leucine-rich repeat (NBS-LRR) genes are important for plant development and disease resistance. Although genome-wide studies of NBS-encoding genes have been performed in several species, the evolution, structure, expression, and function of these genes remain unknown in radish (Raphanus sativus L.). A recently released draft R. sativus L. reference genome has facilitated the genome-wide identification and characterization of NBS-encoding genes in radish. RESULTS: A total of 225 NBS-encoding genes were identified in the radish genome based on the essential NB-ARC domain through HMM search and Pfam database, with 202 mapped onto nine chromosomes and the remaining 23 localized on different scaffolds. According to a gene structure analysis, we identified 99 NBS-LRR-type genes and 126 partial NBS-encoding genes. Additionally, 80 and 19 genes respectively encoded an N-terminal Toll/interleukin-like domain and a coiled-coil domain. Furthermore, 72% of the 202 NBS-encoding genes were grouped in 48 clusters distributed in 24 crucifer blocks on chromosomes. The U block on chromosomes R02, R04, and R08 had the most NBS-encoding genes (48), followed by the R (24), D (23), E (23), and F (17) blocks. These clusters were mostly homogeneous, containing NBS-encoding genes derived from a recent common ancestor. Tandem (15 events) and segmental (20 events) duplications were revealed in the NBS family. Comparative evolutionary analyses of orthologous genes among Arabidopsis thaliana, Brassica rapa, and Brassica oleracea reflected the importance of the NBS-LRR gene family during evolution. Moreover, examinations of cis-elements identified 70 major elements involved in responses to methyl jasmonate, abscisic acid, auxin, and salicylic acid. According to RNA-seq expression analyses, 75 NBS-encoding genes contributed to the resistance of radish to Fusarium wilt. A quantitative real-time PCR analysis revealed that RsTNL03 (Rs093020) and RsTNL09 (Rs042580) expression positively regulates radish resistance to Fusarium oxysporum, in contrast to the negative regulatory role for RsTNL06 (Rs053740). CONCLUSIONS: The NBS-encoding gene structures, tandem and segmental duplications, synteny, and expression profiles in radish were elucidated for the first time and compared with those of other Brassicaceae family members (A. thaliana, B. oleracea, and B. rapa) to clarify the evolution of the NBS gene family. These results may be useful for functionally characterizing NBS-encoding genes in radish.

Dilation-Responsive Microshape Programing Prevents Vascular Graft Stenosis.

Shape memory materials have been successfully applied to minimally invasive implantation of medical devices. However, organ-movement-specific shape programing at a microscale level has never been demonstrated despite significant unmet needs. As vein-to-artery grafting induces vein dilation and stenosis, a polymeric self-enclosable external support (SES) is designed to wrap the vascular out-wall. Its micropores are programmed to increase sizes and interconnections upon dilation. Vessel dilation promotes venous maturation, but overdilation induces stenosis by disturbed blood flow. Therefore, the unique elastic shape-fixity of SES provides a foundation to enable a stable microscale shape transition by maintaining the vein dilation. The shape transition of micropore architecture upon dilation induces beneficial inflammation, thereby regenerating vasa vasorum and directing smooth muscle cell migration toward adventitia with the consequent muscle reinforcement of veins. This game-changer approach prevents the stenosis of vein-to-artery grafting by rescuing ischemic disorders and promoting arterial properties of veins.

Color three-dimensional imaging based on patterned illumination using a negative pinhole array.

Reflectance confocal microscopy is widely used for non-destructive optical three-dimensional (3D) imaging. In confocal microscopy, a stack of sequential two-dimensional (2D) images with respect to the axial position is typically needed to reconstruct a 3D image. As a result, in conventional confocal microscopy, acquisition speed is often limited by the rate of mechanical scanning in both the transverse and axial directions. We previously reported a high-speed parallel confocal detection method using a pinhole array for color 3D imaging without any mechanical scanners. Here, we report a high-speed color 3D imaging method based on patterned illumination employing a negative pinhole array, whose optical characteristics are the reverse of the conventional pinhole array for transmitting light. The negative pinhole array solves the inherent limitation of a conventional pinhole array, i.e., low transmittance, meaning brighter color images with abundant color information can be acquired. We also propose a 3D image processing algorithm based on the 2D cross-correlation between the acquired image and filtering masks, to produce an axial response. By using four-different filtering masks, we were able to increase the sampling points in calculation of height and enhance the lateral resolution of the color acquisition by a factor of four. The feasibility of high-speed non-contact color 3D measurement with the improved lateral resolution and brightness provided by the negative pinhole array was demonstrated by imaging various specimens. We anticipate that this high-speed color 3D measurement technology with negative pinhole array will be a useful tool in a variety of fields where rapid and accurate non-contact measurement are required, such as industrial inspection and dental scanning.

Optical Oxygen Sensor Patch Printed with Polystyrene Microparticles-based Ink on Flexible Substrate.

Optical oxygen sensors based on photoluminescence quenching have gained increasing attention as a superior method for continuous monitoring of oxygen in a growing number of applications. A simple and low-cost fabrication technique was developed to produce sensor arrays capable of two-dimensional oxygen tension measurement. Sensor patches were printed on polyvinylidene chloride film using an oxygen-sensitive ink cocktail, prepared by immobilizing Pt(II) mesotetra(pentafluorophenyl)porphine (PtTFPP) in monodispersed polystyrene microparticles. The dispersion media of the ink cocktail, high molecular weight polyvinyl pyrrolidone suspended in 50% ethanol (v/v in water), allowed adhesion promotion and compatibility with most common polymeric substrates. Ink phosphorescence intensity was found to vary primarily with fluorophore concentration and to a lesser extent with polystyrene particle size. The sensor performance was investigated as a function of oxygen concentrations employing two different techniques: a multi-frequency phase fluorometer and smart phone-based image acquisition. The printed sensor patch showed fast and repetitive response over 0-21% oxygen concentrations with high linearity (with R2 >0.99) in a Stern-Volmer plot, and sensitivity of I0/I21 >1.55. The optical sensor response on a surface was investigated further using two-dimensional images which were captured and analyzed under different oxygen environment. Printed sensor patch along with imaging read-out technique make an ideal platform for early detection of surface wounds associated with tissue oxygen.

Spatial variation of pharmaceuticals in the unit processes of full-scale municipal wastewater treatment plants in Korea.

Several reports have elucidated the removal of pharmaceutical residues in municipal wastewater treatment plants (WWTPs). However, there remains a need to determine the spatial distribution of pharmaceuticals in the unit processes of full-scale municipal WWTPs. Herein, spatial variations of fifteen pharmaceuticals in the unit processes of four full-scale municipal WWTPs were assessed by analyzing both solid and liquid samples. Furthermore, different pathways of each pharmaceutical such as biodegradation, adsorption, deconjugation, and electrostatic interaction were investigated. Pharmaceutical mass loading were measured at various points for the different unit process and evaluated using liquid chromatography-tandem mass spectrometry. The average mass loading of acetaminophen and caffeine decreased tremendously in the first biological treatment process regardless of the process configuration. In contrast, a temporary increase was observed in the mass loading of ibuprofen in the anaerobic and/or anoxic processes, which was presumably caused by deconjugation. Additionally, the adverse effect of coagulation on ibuprofen removal was validated. The major removal mechanism for the selected antibiotics, except for sulfamethoxazole, was the adsorption by biosolids due to electrostatic interaction. Subsequently, a drastic decrease was observed in their mass loadings in the solid-liquid separation process of the WWTPs. The membrane bioreactor (MBR) shows excellent capability for mitigation of pharmaceuticals in municipal wastewater because it comprises a high concentration of biosolids that act as adsorbents. The evaluation of the spatial variations of the selected pharmaceuticals in different unit processes provides valuable information on their behavior and removal mechanisms.

Anti-Atherogenic Effect of Stem Cell Nanovesicles Targeting Disturbed Flow Sites.

Atherosclerosis development leads to irreversible cascades, highlighting the unmet need for improved methods of early diagnosis and prevention. Disturbed flow formation is one of the earliest atherogenic events, resulting in increased endothelial permeability and subsequent monocyte recruitment. Here, a mesenchymal stem cell (MSC)-derived nanovesicle (NV) that can target disturbed flow sites with the peptide GSPREYTSYMPH (PREY) (PMSC-NVs) is presented which is selected through phage display screening of a hundred million peptides. The PMSC-NVs are effectively produced from human MSCs (hMSCs) using plasmid DNA designed to functionalize the cell membrane with PREY. The potent anti-inflammatory and pro-endothelial recovery effects are confirmed, similar to those of hMSCs, employing mouse and porcine partial carotid artery ligation models as well as a microfluidic disturbed flow model with human carotid artery-derived endothelial cells. This nanoscale platform is expected to contribute to the development of new theragnostic strategies for preventing the progression of atherosclerosis.

High-speed color three-dimensional measurement based on parallel confocal detection with a focus tunable lens.

Reflectance confocal microscopy is a widely used optical imaging technique for non-destructive three-dimensional (3D) surface measurement. In confocal microscopy, a stack of two-dimensional (2D) images along the axial position is used for 3D reconstruction. This means the speed of 3D volumetric acquisition is limited by the beam scanning and the mechanical axial scanning. To achieve fast volumetric imaging, simultaneous multiple point scanning by parallelizing the beam instead of transverse point scanning can be considered, using a pinhole array. Previously, we developed a direct-view confocal microscope with a focus tunable lens (FTL) to produce a monochrome 3D surface profile of a sample without any mechanical scanning. Here, we report a high-speed color 3D measurement method based on parallel confocal detection. The proposed method produces a color 3D image of an object by acquiring 180 2D color images with an acquisition time of 1 second. We also visualized the color information of the object by overlaying the color obtained with a color area detector and a white LED illumination on top of the 3D surface profile. In addition, we designed an improved optical system to reduce artifacts caused by internal reflections and developed a new algorithm for noise-resistant 3D measurements. The feasibility of the proposed non-contact high-speed color 3D measurement for use in industrial or biomedical fields was demonstrated by imaging the color 3D shapes of various specimens. We anticipate that this technology can be utilized in various fields, where rapid 3D surface profiles with color information are required.

Predisposing, enabling, and need factors associated with utilization of institutional delivery services: A community-based cross-sectional study in far-western Nepal.

Use of institutional delivery services can be effective in reducing maternal and infant mortality. In Nepal, however, the majority of women deliver at home. Using Andersen's behavioral model of use of health care services, this cross-sectional study aimed to identify factors associated with use of institutional delivery services in four villages and one municipality in Kailali district, Nepal. Mothers (N = 500) who had given birth in the 5 years preceding the survey (conducted between January and February 2015) were randomly selected by cluster sampling and interviewed using a semi-structured questionnaire. Bivariate analyses and multivariate hierarchical logistic regression analyses were performed. Among the women surveyed, 65.6% had used institutional delivery services for their last delivery, a higher proportion than the national average. Primiparity, having a secondary or higher education level, living in the Durgauli village, having husbands with occupations other than agriculture or professional/technical jobs, and having attended four or more antenatal care (ANC) visits had significantly increased use of institutional deliveries. Also, belonging to the richest 20% of the community and having experienced pregnancy complications were marginally significantly associated. These findings demonstrate the need for improving mother's education, encouraging them to attend ANC visits and addressing disparities between different regions.

Highly Dispersed Pt Nanoparticles for the Production of Aromatic Hydrocarbons by the Catalytic Degrading of Alkali Lignin.

Aromatic hydrocarbons were produced from lignin, a complex natural amorphous polymer commonly regarded as by-product of the pulping process and from biofuel production. The catalytic decomposition of lignin using supported Pt catalysts was performed to produce small molecule hydrocarbons. Aromatic small-molecule hydrocarbon products were identified and quantified using GC/MS and GC-FID, which demonstrated that 27.6% of aromatic hydrocarbons were obtained from the activated carbon-supported Pt (Pt/AC) catalyst which had the highest Pt surface area.

Catalytic Depolymerization of Alkali Lignin Using Supported Pt Nanoparticle Catalysts.

Alkali lignin, a byproduct of the pulping process, was depolymerized using Pt nanoparticle catalysts. A depolymerized lignin with a lower molecular weight was obtained and characterized with GPC and NMR. 31P-NMR using OH-sensitive probing molecules showed the formation of guaiacyl OHs during the reaction, indicating the cleavage of guaiacyl ether bonds.

Co-delivery of protein and small molecule therapeutics using nanoparticle-stabilized nanocapsules.

Combination therapy employing proteins and small molecules provides access to synergistic treatment strategies. Co-delivery of these two payloads is challenging due to the divergent physicochemical properties of small molecule and protein cargos. Nanoparticle-stabilized nanocapsules (NPSCs) are promising for combination treatment strategies since they have the potential to deliver small molecule drugs and proteins simultaneously into the cytosol. In this study, we loaded paclitaxel into the hydrophobic core of the NPSC and self-assembled caspase-3 and nanoparticles on the capsule surface. The resulting combination NPSCs showed higher cytotoxicity than either of the single agent NPSCs, with synergistic action established using combination index values.

Regulating exocytosis of nanoparticles via host-guest chemistry.

Prolonged retention of internalized nanoparticulate systems inside cells improves their efficacy in imaging, drug delivery, and theranostic applications. Especially, regulating exocytosis of the nanoparticles is a key factor in the fabrication of effective nanocarriers for chemotherapeutic treatments but orthogonal control of exocytosis in the cellular environment is a major challenge. Herein, we present the first example of regulating exocytosis of gold nanoparticles (AuNPs), a model drug carrier, by using a simple host-guest supramolecular system. AuNPs featuring quaternary amine head groups were internalized into the cells through endocytosis. Subsequent in situ treatment of a complementary cucurbit[7]uril (CB[7]) to the amine head groups resulted in the AuNP-CB[7] complexation inside cells, rendering particle assembly. This complexation induced larger particle assemblies that remained sequestered in the endosomes, inhibiting exocytosis of the particles without any observed cytotoxicity.

Gold nanoparticles for nucleic acid delivery.

Gold nanoparticles provide an attractive and applicable scaffold for delivery of nucleic acids. In this review, we focus on the use of covalent and noncovalent gold nanoparticle conjugates for applications in gene delivery and RNA-interference technologies. We also discuss challenges in nucleic acid delivery, including endosomal entrapment/escape and active delivery/presentation of nucleic acids in the cell.

Acylsulfonamide-Functionalized Zwitterionic Gold Nanoparticles for Enhanced Cellular Uptake at Tumor pH.

A nanoparticle design featuring pH-responsive alkoxyphenyl acylsulfonamide ligands is reported herein. As a result of ligand structure, this nanoparticle is neutral at pH 7.4, becoming positively charged at tumor pH (<6.5). The particle uptake and cytotoxicity increase over this pH range. This pH-controlled uptake and toxicity makes this particle a promising tool for tumor selective therapy.

Inorganic Nanoparticles for Therapeutic Delivery: Trials, Tribulations and Promise.

Inorganic nanomaterials have a wide array of physical and structural properties that make them attractive candidates for imaging and therapeutic delivery. Nanoparticle platforms have been intensely studied for these applications, and examples are starting to enter the clinic. This review looks at why inorganic particles provide promising platforms for biomedicine, and what issues need to be addressed for them to reach their potential.