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Abstract Aminopyrrolnitrin (APRN), a natural halogenated phenylpyrrole derivative (HPD), has strong antifungal and antiparasitic activities. Additionally, it showed 2.8-fold increased photostability compared to pyrrolnitrin, a commercially available HPD with antimicrobial activity. For microbial production of APRN, we first engineered anthranilate phosphoribosyltransferase encoded by trpD from Corynebacterium glutamicum, resulting in a TrpDA162D mutation that exhibits feedback-resistant against l-tryptophan and higher substrate affinity compared to wild-type TrpD. Plasmid-borne expression of trpD A162D in C. glutamicum TP851 strain with two copies of trpD A162D in the genome led to the production of 3.1 g/L l-tryptophan in flask culture. Subsequent step for l-tryptophan chlorination into 7-chloro-l-tryptophan was achieved by introducing diverse sources of genes encoding tryptophan 7-halogenase (PrnA or RebH) and flavin reductase (Fre, PrnF, or RebF). The combined expression of prnA from Serratia grimesii or Serratia plymuthica with flavin reductase gene from Escherichia coli, Pseudomonas fluorescens, or Lechevalieria aerocolonigenes yielded higher production of 7-chloro-l-tryptophan in comparison to other sets of two-component systems. In the next step, production of putative monodechloroaminopyrrolnitrin (MDAP) from 7-chloro-l-tryptophan was achieved through the expression of prnB encoding MDAP synthase from S. plymuthica or P. fluorescens. Finally, an artificial APRN biosynthetic pathway was constructed by simultaneously expressing genes coding for tryptophan 7-halogenase, flavin reductase, MDAP synthase, and MDAP halogenase (PrnC) from different microbial sources within the l-tryptophan-producing TP851 strain. As prnC from S. grimesii or S. plymuthica was introduced into the host strain, which carried plasmids expressing prnA from S. plymuthica, fre from E. coli, and prnB from S. plymuthica, APN3639 and APN3638 accumulated 29.5 mg/L and 28.1 mg/L of APRN in the culture broth. This study represents the first report on the fermentative APRN production by metabolically engineered C. glutamicum.

Background/purpose: The long-term outcomes of implants placed in grafted sinuses using recombinant human bone morphogenetic protein-2 (rhBMP-2) are unclear. This study aimed to compare 3- and 5-year implant survival rates and marginal bone loss (MBL) during functional loading. Materials and methods: In this retrospective study, we analyzed 63 implants inserted after maxillary sinus floor augmentation (MSFA) in 45 patients between January 2016 and April 2019. The outcome variables were: 1) 3- and 5-year cumulative survival rates of the implants and 2) MBL after functional loading. Other assessed variables included patient demographic information, preoperative residual bone height (RBH), surgical site, implant length and diameter, graft material, healing period before loading, prosthetic type, and opposing dentition. Results: The cumulative 3- and 5-year survival rates of the implants were 100% in the rhBMP-2 group and 95.5% and 86.4% in the non-rhBMP-2 group, respectively. The average 3- and 5-year MBL were 1.14 ± 0.67 mm, 1.30 ± 0.74 mm in the rhBMP-2 group and 1.68 ± 0.90 mm, 2.27 ± 1.29 mm in the non-rhBMP-2 group, respectively. Significant differences were observed between 3 and 5 years between the two groups. Conclusion: Addition of the rhBMP-2 to the graft materials positively affects implant placement in the grafted maxillary sinus in terms of implant survival and MBL when preoperative RBH is unfavorable.

Background: Probiotics, which are live microorganisms that, when given in sufficient quantities, promote the host’s health, have drawn a lot of interest for their ability to enhance gut health. Enterococcus faecalis, a member of the human gut microbiota, has shown promise as a probiotic candidate due to its functional attributes. However, safety concerns associated with certain strains warrant comprehensive evaluation before therapeutic application. Materials and Methods: In this study, E. faecalis EF-2001, originally isolated from fecal samples of a healthy human infant, was subjected to a multi-faceted assessment for its safety and probiotic potential. In silico analysis, CAZyme, biosynthetic, and stress-responsive proteins were identified. Results: The genome lacked biogenic amine genes but contained some essential amino acid and vitamin synthetic genes, and carbohydrate-related enzymes essential for probiotic properties. The negligible difference of 0.03% between the 1st and 25th generations indicates that the genetic information of the E. faecalis EF-2001 genome remained stable. The live E. faecalis EF-2001 (E. faecalis EF-2001L) demonstrated low or no virulence potential, minimal D-Lactate production, and susceptibility to most antibiotics except some aminoglycosides. No bile salt deconjugation or biogenic amine production was observed in an in vitro assay. Hemolytic activity assessment showed a β-hemolytic pattern, indicating no red blood cell lysis. Furthermore, the EF-2001L did not produce gelatinase and tolerated simulated gastric and intestinal fluids in an in vitro study. Similarly, heat-killed E. faecalis EF-2001 (E. faecalis EF-2001HK) exhibits tolerance in both acid and base conditions in vitro. Further, no cytotoxicity of postbiotic EF-2001HK was observed in human colorectal adenocarcinoma HT-29 cells. Conclusions: These potential properties suggest that probiotic and postbiotic E. faecalis EF-2001 could be considered safe and retain metabolic activity suitable for human consumption.

Abstract Cancer is a disease caused by abnormal cell growth that spreads through other parts of the body and threatens life by destroying healthy tissues. Therefore, numerous techniques have been employed not only to diagnose and monitor the progress of cancer in a precise manner but also to develop appropriate therapeutic agents with enhanced efficacy and safety profiles. In this regard, molecularly imprinted polymers (MIPs), synthetic receptors that recognize targeted molecules with high affinity and selectivity, have been intensively investigated as one of the most attractive biomaterials for theragnostic approaches. This review describes diverse synthesis strategies to provide the rationale behind these synthetic antibodies and provides a selective overview of the recent progress in the in vitro and in vivo targeting of cancer biomarkers for diagnosis and therapeutic applications. Taken together, the topics discussed in this review provide concise guidelines for the development of novel MIP-based systems to diagnose cancer more precisely and promote successful treatment. Graphical Abstract Molecularly imprinted polymers (MIPs), synthetic receptors that recognize targeted molecules with high affinity and selectivity, have been intensively investigated as one of the most attractive biomaterials for cancer theragnostic approaches. This review describes diverse synthesis strategies to provide the rationale behind these synthetic antibodies and provides a selective overview of the recent progress in the in vitro and in vivo targeting of cancer biomarkers for diagnosis and therapeutic applications. The topics discussed in this review aim to provide concise guidelines for the development of novel MIP-based systems to diagnose cancer more precisely and promote successful treatment.

Advances in nano/micro technologies in recent years have significantly improved biosensors in terms of their viability for biomedical purposes, from diagnostic to therapeutic applications, allowing for effective early detection and personalized treatment modalities [...]

The proliferation and migration of vascular smooth muscle cells (VSMCs) are important factors in the occurrence of cardiovascular diseases, such as blood flow abnormalities, stroke and atherosclerosis. Evening primrose, known as Oenothera biennis, is a plant native to Korea that exerts physiological activities, such as antioxidant effects, the inhibition of lipid accumulation and the prevention of muscle atrophy. However, the function of evening primrose stem (EVP) in the regulation of VSMC proliferation and migration and the underlying mechanisms have not been identified. In this study, the effect of EVP on the platelet-derived growth factor (PDGF)-induced proliferation and migration of VSMCs was investigated. The results show that PDGF-BB-induced proliferation of VSMCs was inhibited by EVP at concentrations of 25, 50 or 100 μg/mL in a concentration-dependent manner, and a migration assay showed that EVP inhibited cell migration. Cell cycle analysis was performed to confirm the mechanism by which cell proliferation and migration was inhibited. The results indicate that proteins involved in the cell cycle, such as cyclin, CDK and phosphorylated Rb, were downregulated by EVP at concentrations of 100 μg/mL, thereby increasing the proportion of cells in the G0/G1 phase and inhibiting cell cycle progression. In the PDGF receptor (PDGFR) signaling pathway, phosphorylation of the PDGFR was inhibited by EVP at concentrations of 100 μg/mL, and PLCγ phosphorylation was also decreased. The PDGF-BB-induced effect of EVP on the proliferation of VSMCs involved the inhibition of Akt phosphorylation and the reduction in the phosphorylation of MAPK proteins such as ERK, P38 and JNK. In conclusion, the results demonstrate that EVP inhibited PDGF-BB-induced VSMC proliferation and migration by regulating cell-cycle-related proteins.

Abstract The topographical interface of the extracellular environment has been appreciated as a principal biophysical regulator for modulating cell functions, such as adhesion, migration, proliferation, and differentiation. Despite the existed approaches that use two-dimensional nanomaterials to provide beneficial effects, opportunities evaluating their impact on stem cells remain open to elicit unprecedented cellular responses. Herein, we report an ultrathin cell-culture platform with potential-responsive nanoscale biointerfaces for monitoring mesenchymal stem cells (MSCs). We designed an intriguing nanostructured array through self-assembly of graphene oxide sheets and subsequent lithographical patterning method to produce chemophysically defined regions. MSCs cultured on anisotropic micro/nanoscale patterned substrate were spontaneously organized in a highly ordered configuration mainly due to the cell-repellent interactions. Moreover, the spatially aligned MSCs were spontaneously differentiated into smooth muscle cells upon the specific crosstalk between cells. This work provides a robust strategy for directing stem cells and differentiation, which can be utilized as a potential cell culture platform to understand cell–substrate or cell–cell interactions, further developing tissue repair and stem cell-based therapies. Graphical Abstract

Abstract Hyperloop is a new concept of ground transportation. In Hyperloop, travelling occurs in near-vacuum tubes under 0.001 atm at a subsonic speed of up to 1200 km/h. During acceleration to and driving at a subsonic speed, magnetic levitation is employed. Thus far, various levitation technologies in existing high-speed maglev trains have been considered. Among those technologies, superconducting (SC) electrodynamic suspension (EDS) is a highly effective levitation system for Hyperloop owing to its advantages of a large levitation gap, levitation stability, and control being unnecessary. However, analyzing an EDS system requires the electromagnetic transient analysis of complex three-dimensional (3D) features, and its computational load generally limits the use of numerical methods, such as the 3D finite element method (FEM) or dynamic circuit theory. In this study, a novel model that can rapidly and accurately calculate the frequency-dependent equivalent inductance was developed. The developed model was then applied to design an EDS system using the decoupled resistance-inductance equations of levitation coils. Next, levitation coils of SC-EDS were designed and analyzed for use in Hyperloop. The obtained results were compared with the FEM results to validate the developed model. In addition, the model was experimentally validated by measuring currents induced by moving pods.

Abstract This study aimed to analyze the rates and risk factors of postoperative mortality among 560,954 patients who underwent total knee arthroplasty (TKA) in Korea. The National Health Insurance Service-Health Screening database was used to analyze 560,954 patients who underwent TKA between 2005 and 2018. In-hospital, ninety-day, and one-year postoperative mortality, and their association with patient’s demographic factors and various comorbidities (ie., cerebrovascular disease, congestive heart failure, and myocardial infarction) were assessed. In-hospital, ninety-day and one-year mortality rates after TKA were similar from 2005 to 2018. The risk of in-hospital mortality increased with comorbidities like cerebrovascular disease (hazard ratio [HR] = 1.401; 95% confidence interval [CI] = 1.064–1.844), congestive heart failure (HR = 2.004; 95% CI = 1.394 to 2.881), myocardial infarction (HR = 2.111; 95% CI = 1.115 to 3.998), and renal disease (HR = 2.641; 95% CI = 1.348–5.173). These co-morbidities were also independent predictors of ninety-day and one-year mortality. Male sex and old age were independent predictors for ninety-day and one-year mortality. And malignancy was risk factor for one-year mortality. The common preoperative risk factors for mortality in all periods were male sex, old age, cerebrovascular disease, congestive heart failure, myocardial infarction, and renal disease. Malignancy was identified as risk factor for one-year mortality. Patients with these comorbidities should be provided better perioperative care.

Liver cancer is a prevalent global health concern with a poor 5-year survival rate upon diagnosis. Current diagnostic techniques using the combination of ultrasound, CT scans, MRI, and biopsy have the limitation of detecting detectable liver cancer when the tumor has already progressed to a certain size, often leading to late-stage diagnoses and grim clinical treatment outcomes. To this end, there has been tremendous interest in developing highly sensitive and selective biosensors to analyze related cancer biomarkers in the early stage diagnosis and prescribe appropriate treatment options. Among the various approaches, aptamers are an ideal recognition element as they can specifically bind to target molecules with high affinity. Furthermore, using aptamers, in conjunction with fluorescent moieties, enables the development of highly sensitive biosensors by taking full advantage of structural and functional flexibility. This review will provide a summary and detailed discussion on recent aptamer-based fluorescence biosensors for liver cancer diagnosis. Specifically, the review focuses on two promising detection strategies: (i) Förster resonance energy transfer (FRET) and (ii) metal-enhanced fluorescence for detecting and characterizing protein and miRNA cancer biomarkers.

Aromatic aldehydes, including 4-hydroxybenzaldehyde (4-HB aldehyde), protocatechuic (PC) aldehyde, and vanillin, are used as important flavors, fragrances, and pharmaceutical precursors and have several biological and therapeutic effects. Production of aromatic aldehydes in microbial hosts poses a challenge due to its rapid and endogenous reduction to alcohols. To address this hurdle, prospecting of the genome of Corynebacterium glutamicum yielded 27 candidate proteins that were used in comprehensive screening with a 4-hydroxybenzyl (4-HB) alcohol–producing strain. We identified that NCgl0324 has aromatic aldehyde reductase activity and contributed to 4-HB aldehyde reduction in vivo since the NCgl0324 deletion strain HB-Δ0324 produced 1.36 g/L of 4-HB aldehyde, that is, about 188% more than its parental strain. To demonstrate that NCgl0324 knockout can also improve production of PC aldehyde and vanillin, first, a basal MA303 strain that produces protocatechuate was engineered from 4-hydroxybenzoate-synthesizing C. glutamicum APS963, followed by deletion of NCgl0324 to generate PV-Δ0324. The PC aldehyde/alcohol or vanillin/vanillyl alcohol biosynthetic pathways, respectively, were able to be expanded from protocatechuate upon introduction of carboxylic acid reductase (CAR) and catechol O-methyltransferase encoded by a mutated comtm gene. In shake flask culture, the resulting NCgl0324 deletion strains PV-IΔ0324 and PV-IYΔ0324 were shown to produce 1.18 g/L PC aldehyde and 0.31 g/L vanillin, respectively. Thus, modulation of the identified NCgl0324 gene was shown to have the potential to boost production of valuable aromatic aldehydes and alcohols.

One of the main concerns in the structural integrity of offshore pipelines is mechanical damage from external loads. Pipelines are exposed to fatigue failure in welded joints due to geometric discontinuity. In addition, fatigue loads such as currents, waves, and platform motions may cause significant plastic deformation and fracture or leakage within a relatively low-cycle regime. The 2007 ASME Div. 2 Code adopts the master S–N curve for the fatigue evaluation of welded joints based on the mesh-insensitive structural stress. An extension to the master S–N curve was introduced to evaluate the low-cycle fatigue strength. This structural strain method uses the tensile properties of the material. However, the monotonic tensile properties have limitations in describing the material behavior above the elastic range because most engineering materials exhibit hardening or softening behavior under cyclic loads. The goal of this study is to extend the cyclic stress-strain behavior to the structural strain method. To this end, structural strain-based procedure was established while considering the cyclic stress-strain behavior and compared to the structural strain method with monotonic tensile properties. Finally, the improved prediction method was validated using fatigue test data from full-scale girth-welded pipes.

Background: Chuna Manual Therapy (CMT) has been widely used in Korea, and coverage in Korean National Health Insurance (NHI) was finally implemented in 2019. The objectives of this study were to analyze the process of NHI coverage for CMT qualitatively, and to summarize important roles, streams, and implications regarding its inclusion in the modern public health insurance system. Methods: Related literature was collected and 8 key personnel involved in the policy-making process were qualitatively interviewed, and Zahariadis’ version of the Multiple Streams Framework (MSF) was applied to analyze the policy agenda setting and the roles of stakeholders. Results: Through the collaborative efforts of various stakeholders, a pilot coverage project for CMT was implemented in 2017, and coverage was expanded nationwide in 2019. MSF showed that it was mainly achieved through three streams: governmental change (political stream), demand from the general public and KM doctors (problem stream), and strengthening/reinforcement of the feasibility and acceptability of the policy (policy steam). Also, the roles of policy entrepreneurs and resulting changes were shown to be significant for the overall process. Conclusion: NHI coverage for CMT was realized through collective policy and research efforts from the government and academic sectors. The roles of stakeholders were shown to be significant in the overall process, and documentation of their involvement is hoped to be of use of other countries that utilize traditional and/or manual medicine.

Corynebacterium glutamicum is used for the million-ton-scale production of amino acids. Valorization of sidestreams from agri- and aqua-culture has focused on the production of biofuels and carboxylic acids. Nitrogen present in various amounts in sidestreams may be valuable for the production of amines, amino acids and other nitrogenous compounds. Metabolic engineering of C. glutamicum for valorization of agri- and aqua-culture sidestreams addresses to bridge this gap. The product portfolio accessible via C. glutamicum fermentation primarily features amino acids and diamines for large-volume markets in addition to various specialty amines. On the one hand, this review covers metabolic engineering of C. glutamicum to efficiently utilize components of various sidestreams. On the other hand, examples of the design and implementation of synthetic pathways not present in native metabolism to produce sought after nitrogenous compounds will be provided. Perspectives and challenges of this concept will be discussed.

Over the past two decades, lanthanide-based upconversion nanoparticles (UCNPs) have been fascinating scientists due to their ability to offer unprecedented prospects to upconvert tissue-penetrating near-infrared light into color-tailorable optical illumination inside biological matter. In particular, luminescent behavior UCNPs have been widely utilized for background-free biorecognition and biosensing. Currently, a paramount challenge exists on how to maximize NIR light harvesting and upconversion efficiencies for achieving faster response and better sensitivity without damaging the biological tissue upon laser assisted photoactivation. In this review, we offer the reader an overview of the recent updates about exciting achievements and challenges in the development of plasmon-modulated upconversion nanoformulations for biosensing application.

Obesity is a disease in which fat is abnormally or excessively accumulated in the body, and many studies have been conducted to overcome it with various techniques. In this study, we evaluated whether micro-current stimulation (MCS) can be applied to prevent obesity by regulating the adipogenesis through 3T3-L1 cells and ob/ob mice. To specify the intensity of MCS, Oil Red O staining was conducted with various intensities of MCS. Based on these, subsequent experiments used 200 and 400 μA for the intensity of MCS. The expressions of insulin signaling pathway-related proteins, including phosphorylation of IGF-1 and IR, were decreased in all MCS groups, and in turn, downstream signals such as Akt and ERK were decreased. In addition, MCS reduced the nucleus translocation of PPAR-γ and decreased the protein expression of C/EBP-α. In the ob/ob mouse model, MCS reduced body weight gain and abdominal adipose tissue volume. In particular, the concentration of triglycerides in serum was also decreased. Taken together, our findings showed that MCS inhibited lipid accumulation by regulating insulin signaling in 3T3-L1, and it was effective at reducing body weight and adipose tissue volume in ob/ob mice. These suggest that MCS may be a useful treatment approach for obesity.

Abstract γ-Aminobutyric acid (GABA) is an important inhibitory neurotransmitter in the central nervous system (CNS), which acts as a major biomarker for neurological disorders such as Parkinson’s disease and Meningitis. To this end, the precise measurement of GABA molecule arisen as an important subject for the effective diagnosis and treatment of neurological disorders. However, yet highly sensitive biosensor systems which can analyze a wide range of GABA molecule in a fast response manner have not been reported. In this study, for the first time, a silicon nanowire field-effect transistor (FET) device based immunosensor was developed to detect GABA molecule. Zig-zag shaped silicon nanowires has been fabricated by electron beam lithography and the electrical property p-type FET device was validated through semiconductor analyzer. The optimal immobilizing condition of antibody against GABA molecule was determined by the fluorescent signal measurement. Various concentrations of GABA ranging from 970 fM to 9.7 μM were sensitively measured by conductance change on silicon nanowire-based through the immunoreactions. Further, owing to the ease of miniaturization and label-free system, we believe that the suggested device system has a potential to be utilized for an implantable biosensor to detect neurotransmitter in the brain and can create new opportunities in the field of diagnosis and treatment of neurological disorders.

Exosomes have been gaining attention for early cancer diagnosis owing to their biological functions in cells. Several studies have reported the relevance of exosomes in various diseases, including pancreatic cancer, retroperitoneal fibrosis, obesity, neurodegenerative diseases, and atherosclerosis. Particularly, exosomes are regarded as biomarkers for cancer diagnosis and can be detected in biofluids, such as saliva, urine, peritoneal fluid, and blood. Thus, exosomes are advantageous for cancer liquid biopsies as they overcome the current limitations of cancer tissue biopsies. Several studies have reported methods for exosome isolation, and analysis for cancer diagnosis. However, further clinical trials are still required to determine accurate exosome concentration quantification methods. Recently, various biosensors have been developed to detect exosomal biomarkers, including tumor-derived exosomes, nucleic acids, and proteins. Among these, the exact quantification of tumor-derived exosomes is a serious obstacle to the clinical use of liquid biopsies. Precise detection of exosome concentration is difficult because it requires clinical sample pretreatment. To solve this problem, the use of the nanobiohybrid material-based biosensor provides improved sensitivity and selectivity. The present review will discuss recent progress in exosome biosensors consisting of nanomaterials and biomaterial hybrids for electrochemical, electrical, and optical-based biosensors.

Coenzyme Q10 (CoQ10) serves as an electron carrier in aerobic respiration and has become an interesting target for biotechnological production due to its antioxidative effect and benefits in supplementation to patients with various diseases. For the microbial production, so far only bacteria have been used that naturally synthesize CoQ10 or a related CoQ species. Since the whole pathway involves many enzymatic steps and has not been fully elucidated yet, the set of genes required for transfer of CoQ10 synthesis to a bacterium not naturally synthesizing CoQ species remained unknown. Here, we established CoQ10 biosynthesis in the non-ubiquinone-containing Gram-positive Corynebacterium glutamicum by metabolic engineering. CoQ10 biosynthesis involves prenylation and, thus, requires farnesyl diphosphate as precursor. A carotenoid-deficient strain was engineered to synthesize an increased supply of the precursor molecule farnesyl diphosphate. Increased farnesyl diphosphate supply was demonstrated indirectly by increased conversion to amorpha-4,11-diene. To provide the first CoQ10 precursor decaprenyl diphosphate (DPP) from farnesyl diphosphate, DPP synthase gene ddsA from Paracoccus denitrificans was expressed. Improved supply of the second CoQ10 precursor, para-hydroxybenzoate (pHBA), resulted from metabolic engineering of the shikimate pathway. Prenylation of pHBA with DPP and subsequent decarboxylation, hydroxylation, and methylation reactions to yield CoQ10 was achieved by expression of ubi genes from Escherichia coli. CoQ10 biosynthesis was demonstrated in shake-flask cultivation and verified by liquid chromatography mass spectrometry analysis. To the best of our knowledge, this is the first report of CoQ10 production in a non-ubiquinone-containing bacterium.

Since 2010, DNA nanotechnology has advanced rapidly, helping overcome limitations in the use of DNA solely as genetic material. DNA nanotechnology has thus helped develop a new method for the construction of biosensors. Among bioprobe materials for biosensors, nucleic acids have shown several advantages. First, it has a complementary sequence for hybridizing the target gene. Second, DNA has various functionalities, such as DNAzymes, DNA junctions or aptamers, because of its unique folded structures with specific sequences. Third, functional groups, such as thiols, amines, or other fluorophores, can easily be introduced into DNA at the 5′ or 3′ end. Finally, DNA can easily be tailored by making junctions or origami structures; these unique structures extend the DNA arm and create a multi-functional bioprobe. Meanwhile, nanomaterials have also been used to advance plasmonic biosensor technologies. Nanomaterials provide various biosensing platforms with high sensitivity and selectivity. Several plasmonic biosensor types have been fabricated, such as surface plasmons, and Raman-based or metal-enhanced biosensors. Introducing DNA nanotechnology to plasmonic biosensors has brought in sight new horizons in the fields of biosensors and nanobiotechnology. This review discusses the recent progress of DNA nanotechnology-based plasmonic biosensors.

Numerous efforts have been made to develop efficient biosensors for detecting analytes in the human body. However, biosensors are often developed on rigid materials, which limits their application on skin, organs, and other tissues in the human body where good flexibility is required. Developing flexible materials for biosensors that can be used on soft and irregularly shaped surfaces would significantly expand the clinical application of biosensors. In this review, we will provide a selective overview of recently developed flexible electronic devices and their applications for monitoring in vivo metabolite and electrophysiology signals. The article provides guidelines for the development of an in vivo signal monitoring system and emphasizes research from various disciplines for the further development of flexible electronics that can be used in more biomedical applications in the future.

Cytokines are proteins secreted by immune cells. They promote cell signal transduction and are involved in cell replication, death, and recovery. Cytokines are immune modulators, but their excessive secretion causes uncontrolled inflammation that attacks normal cells. Considering the properties of cytokines, monitoring the secretion of cytokines in vivo is of great value for medical and biological research. In this review, we offer a report on recent studies for cytokine detection, especially studies on aptasensors using aptamers. Aptamers are single strand nucleic acids that form a stable three-dimensional structure and have been receiving attention due to various characteristics such as simple production methods, low molecular weight, and ease of modification while performing a physiological role similar to antibodies.

Brominated compounds such as 7-bromo-l-tryptophan (7-Br-Trp) occur in Nature. Many synthetic and natural brominated compounds have applications in the agriculture, food, and pharmaceutical industries, for example, the 20S-proteasome inhibitor TMC-95A that may be derived from 7-Br-Trp. Mild halogenation by cross-linked enzyme aggregates containing FAD-dependent halogenase, NADH-dependent flavin reductase, and alcohol dehydrogenase as well as by fermentation with recombinant Corynebacterium glutamicum expressing the genes for the FAD-dependent halogenase RebH and the NADH-dependent flavin reductase RebF from Lechevalieria aerocolonigenes have recently been developed as green alternatives to more hazardous chemical routes. In this study, the fermentative production of 7-Br-Trp was established. The fermentative process employs an l-tryptophan producing C. glutamicum strain expressing rebH and rebF from L. aerocolonigenes for halogenation and is based on glucose, ammonium and sodium bromide. C. glutamicum tolerated high sodium bromide concentrations, but its growth rate was reduced to half-maximal at 0.09 g L−1 7-bromo-l-tryptophan. This may be, at least in part, due to inhibition of anthranilate phosphoribosyltransferase by 7-Br-Trp since anthranilate phosphoribosyltransferase activity in crude extracts was half-maximal at about 0.03 g L−1 7-Br-Trp. Fermentative production of 7-Br-Trp by recombinant C. glutamicum was scaled up to a working volume of 2 L and operated in batch and fed-batch mode. The titers were increased from batch fermentation in CGXII minimal medium with 0.3 g L−1 7-Br-Trp to fed-batch fermentation in HSG complex medium, where up to 1.2 g L−1 7-Br-Trp were obtained. The product isolated from the culture broth was characterized by NMR and LC-MS and shown to be 7-Br-Trp.

The dynamic responses of a concrete rectangular liquid storage tank on the surface of rigid soil subjected to three-directional earthquake ground motion are investigated with material nonlinearity taken into consideration. Material nonlinearity in concrete is considered using the concrete damage plasticity model. The hydrodynamic pressure due to earthquake ground motion is considered using a finite-element solution of the governing equation for an inviscid and incompressible ideal fluid with the fluid–structure interaction taken into consideration. It was observed from the dynamic analyses that the effects of material nonlinearity and directionality significantly affect the earthquake responses of the considered system. The relative displacement of the structure increased significantly by the nonlinearity of the material. Inclined cracks due to the increased displacement were observed on the long-sided walls. The hydrodynamic pressure can be reduced significantly by the material nonlinearity and is influenced by the directionality of an earthquake’s ground motion. The base shear and overturning moment due to the hydrodynamic pressure and the resulting impulsive mass and corresponding height for a simplified mass-spring analogy are also affected. Because the directionality was observed to have a significant influence on the peak value of the sloshing height, it must be estimated with the directionality considered.

Communication, Ocean And Meteorological Satellite (COMS) Meteorological Imager (MI) images are processed for radiometric and geometric correction from raw image data. When intermediate image data are matched and compared with reference landmark images in the geometrical correction process, various techniques for edge detection can be applied. It is essential to have a precise and correct edged image in this process, since its matching with the reference is directly related to the accuracy of the ground station output images. An edge detection method based on neural networks is applied for the ground processing of MI images for obtaining sharp edges in the correct positions. The simulation results are analyzed and characterized by comparing them with the results of conventional methods, such as Sobel and Canny filters.

The Hyperloop has been developed using various technologies to reach a maximum speed of 1200 km/h. Such technologies include magnetic levitation technologies that are suitable for subsonic driving. In the Hyperloop, the null-flux electrodynamic suspension (EDS) system and superconducting magnets (SCMs) can perform stable levitation without control during high-speed driving. Although an EDS device can be accurately analyzed using numerical analysis methods, such as the 3D finite element method (FEM) or dynamic circuitry theory, its 3D configurations make it difficult to use in various design analyses. This paper presents a new design model that fast analyzes and compares many designs of null-flux EDS devices for the Hyperloop system. For a fast and effective evaluation of various levitation coil shapes and arrangements, the computational process of the induced electromotive force and the coupling effect were simplified using a 2D rectangular coil loop, and the induced current and force equations were written as closed-form solutions using the Fourier analysis. Also, levitation coils were designed, and their characteristics were analyzed and compared with each other. To validate the proposed model, the analyzed force responses for various driving conditions and the changed performance trend by design variables were compared with analyzed FEM results.

The N-functionalized amino acid N-methylanthranilate is an important precursor for bioactive compounds such as anticancer acridone alkaloids, the antinociceptive alkaloid O-isopropyl N-methylanthranilate, the flavor compound O-methyl-N-methylanthranilate, and as a building block for peptide-based drugs. Current chemical and biocatalytic synthetic routes to N-alkylated amino acids are often unprofitable and restricted to low yields or high costs through cofactor regeneration systems. Amino acid fermentation processes using the Gram-positive bacterium Corynebacterium glutamicum are operated industrially at the million tons per annum scale. Fermentative processes using C. glutamicum for N-alkylated amino acids based on an imine reductase have been developed, while N-alkylation of the aromatic amino acid anthranilate with S-adenosyl methionine as methyl-donor has not been described for this bacterium. After metabolic engineering for enhanced supply of anthranilate by channeling carbon flux into the shikimate pathway, preventing by-product formation and enhancing sugar uptake, heterologous expression of the gene anmt encoding anthranilate N-methyltransferase from Ruta graveolens resulted in production of N-methylanthranilate (NMA), which accumulated in the culture medium. Increased SAM regeneration by coexpression of the homologous adenosylhomocysteinase gene sahH improved N-methylanthranilate production. In a test bioreactor culture, the metabolically engineered C. glutamicum C1* strain produced NMA to a final titer of 0.5 g·L−1 with a volumetric productivity of 0.01 g·L−1·h−1 and a yield of 4.8 mg·g−1 glucose.

For the early diagnosis of several diseases, various biomarkers have been discovered and utilized through the measurement of concentrations in body fluids such as blood, urine, and saliva. The most representative analytical method for biomarker detection is an immunosensor, which exploits the specific antigen-antibody immunoreaction. Among diverse analytical methods, surface plasmon resonance (SPR)-based immunosensors are emerging as a potential detection platform due to high sensitivity, selectivity, and intuitive features. Particularly, SPR-based immunosensors could detect biomarkers without labeling of a specific detection probe, as typical immunosensors such as enzyme-linked immunosorbent assay (ELISA) use enzymes like horseradish peroxidase (HRP). In this review, SPR-based immunosensors utilizing noble metals such as Au and Ag as SPR-inducing factors for the measurement of different types of protein biomarkers, including viruses, microbes, and extracellular vesicles (EV), are briefly introduced.

Development of a sensitive and selective detection system for pathogenic viral agents is essential for medical healthcare from diagnostics to therapeutics. However, conventional detection systems are time consuming, resource-intensive and tedious to perform. Hence, the demand for sensitive and selective detection system for virus are highly increasing. To attain this aim, different aspects and techniques have been applied to develop virus sensor with improved sensitivity and selectivity. Here, among those aspects and techniques, this article reviews HIV virus particle detection systems incorporated with nanotechnology to enhance the sensitivity. This review mainly focused on four different detection system including vertically configured electrical detection based on scanning tunneling microscopy (STM), electrochemical detection based on direct electron transfer in virus, optical detection system based on localized surface plasmon resonance (LSPR) and surface enhanced Raman spectroscopy (SERS) using plasmonic nanoparticle.

Graphene, a single atom thick layer of two-dimensional closely packed honeycomb carbon lattice, and its derivatives have attracted much attention in the field of biomedical, due to its unique physicochemical properties. The valuable physicochemical properties, such as high surface area, excellent electrical conductivity, remarkable biocompatibility and ease of surface functionalization have shown great potentials in the applications of graphene-based bioelectronics devices, including electrochemical biosensors for biomarker analysis. In this review, we will provide a selective overview of recent advances on synthesis methods of graphene and its derivatives, as well as its application to electrochemical biosensor development. We believe the topics discussed here are useful, and able to provide a guideline in the development of novel graphene and on graphene-like 2-dimensional (2D) materials based biosensors in the future.

Thermal stratification has continuously caused several piping failures in nuclear power plants since the early 1980s. However, this critical thermal effect was not considered when the old nuclear power plants were designed. Therefore, it is urgent to evaluate this unexpected thermal effect on the structural integrity of piping systems. In this paper, the thermal effects of stratified flow in two different safety injection piping systems were investigated by using a coupled CFD-FE method. Since stratified flow is generally generated by turbulent penetration and/or valve leakage, thermal stress analyses as well as CFD analyses were carried out considering these two primary causes. Numerical results show that the most critical factor governing thermal stratification is valve leakage and that temperature distribution significantly changes according to the leakage path. In particular, in-leakage has a high possibility of causing considerable structural problems in RCS piping.

It is quite essential that requirements allocation and analysis would be done for the electromagnetic compatibility (EMC) of all units when designing a satellite. Although KOMPSAT-2 inherits relatively large portions of the electrical designs from KOMPSAT-1, it has a new instrument and different combinations of sensors and actuators as well as their driving circuitry. Many requirements for the electromagnetic compatibility were modified and newly allocated for KOMPSAT-2. Naturally, they must be justified through analyses from the early stage of the program. In this paper, the EMC compatibility requirements for KOMPSAT2 are presented and verified for their suitability. In addition, some results, which were obtained from various analyses, are presented and discussed.

In the case of a long-stator linear drive, unlike rotative drives for which speed or position sensors are a single unit attached to the shaft, these sensors extend along the guideway. The position signals transmitted from a maglev vehicle cannot meet the need of the real-time propulsion control in the on-ground inverter power substations. In this paper the design of the propulsion inverter control system with a position estimator for driving a long-stator synchronous motor in a high-speed maglev train is proposed. The experiments have been carried out at the 150 m long guideway at the O-song test track. To investigate the performance of the position estimator, the propulsion control system with, and without, the position estimator are compared. The result confirms that the proposed strategy can meet the dynamic property needs of the propulsion inverter control system for driving long-stator linear synchronous motors.

The KOMPSAT (KOrea Multi-Purpose SATellite) has two optical imaging instruments called EOC (Electro-Optical Camera) and OSMI (Ocean Scanning Multispectral Imager). The image data of these instruments are transmitted to ground station and restored correctly after post-processing with the telemetry data transferred from KOMPSAT spacecraft. The major timing information of the KOMPSAT is OBT (On-Board Time) which is formatted by the on-board computer of the spacecraft, based on 1Hz sync. pulse coming from the GPS receiver involved. The OBT is transmitted to ground station with the house-keeping telemetry data of the spacecraft while it is distributed to the instruments via 1553B data bus for synchronization during imaging and formatting. The timing information contained in the spacecraft telemetry data would have direct relation to the image data of the instruments, which should be well explained to get a more accurate image. This paper addresses the timing analysis of the KOMPSAT spacecraft and instruments, including the gyro data timing analysis for the correct restoration of the EOC and OSMI image data at ground station.

In this paper, KOMPSAT satellite launch and deployment operations are discussed. The U.S. Taurus launch vehicle delivers KOMPSAT satellite into the mission orbit directly. Launch and deployment operations is monitored and controlled by several international ground stations including Korean Ground Station (KGS). After separation from launch vehicle, KOMPSAT spacecraft deploys solar array by on-board autonomous stored commands without ground inter-vention and stabilizes the satellite such that solar arrays point to the sun. Autonomous ground communication is designed for KOMPSAT for the early orbit ground contact. KOMPSAT space-craft has capability of handing contingency situation by on-board fault management design to retry deployment sequence.

In tissue engineering and regenerative medicine, monitoring the status of stem cell differentiation is crucial to verify therapeutic efficacy and optimize treatment procedures. However, traditional methods, such as cell staining and sorting, are labor-intensive and may damage the cells. Therefore, the development of noninvasive methods to monitor the differentiation status in situ is highly desirable and can be of great benefit to stem cell-based therapies. Toward this end, nanotechnology has been applied to develop highly-sensitive biosensors to noninvasively monitor the neural differentiation of stem cells. Herein, this article reviews the development of noninvasive nano-biosensor systems to monitor the neural differentiation of stem cells, mainly focusing on optical (plasmonic) and eletrochemical methods. The findings in this review suggest that novel nano-biosensors capable of monitoring stem cell differentiation are a promising type of technology that can accelerate the development of stem cell therapies, including regenerative medicine.

This paper introduces an edge AI-based scene-specific object detection system for long-term traffic management, focusing on analyzing congestion and movement via cameras. It aims to balance fast processing and accuracy in traffic flow data analysis using edge computing. We adapt the YOLOv5 model, with four heads, to a scene-specific model that utilizes the fixed camera’s scene-specific properties. This model selectively detects objects based on scale by blocking nodes, ensuring only objects of certain sizes are identified. A decision module then selects the most suitable object detector for each scene, enhancing inference speed without significant accuracy loss, as demonstrated in our experiments. [ABSTRACT FROM AUTHOR]

Background: Adjuvant therapy prolongs survival in patients with pancreatic ductal adenocarcinoma. However, no clear guidelines are available regarding the oncologic effects of adjuvant therapy (AT) in resected invasive intraductal papillary mucinous neoplasms (IPMN). The aim was to investigate the potential role of AT in patients with resected invasive IPMN. Materials and methods: From 2001 to 2020, 332 patients with invasive pancreatic IPMN were retrospectively reviewed in 15 centres in eight countries. Propensity score-matched and stage-matched survival analyses were conducted. Results: A total of 289 patients were enroled in the study after exclusion (neoadjuvant therapy, unresectable disease, uncertain AT status, and stage IV). A total of 170 patients were enroled in a 1:1 propensity score-matched analysis according to the covariates. In the overall cohort, disease-free survival was significantly better in the surgery alone group than in the AT group (P=0.003), but overall survival (OS) was not (P=0.579). There were no significant differences in OS in the stage-matched analysis between the surgery alone and AT groups (stage I, P=0.402; stage II, P=0.179). AT did not show a survival benefit in the subgroup analysis according to nodal metastasis (N0, P=0.481; N+, P=0.705). In multivariate analysis, node metastasis (hazard ratio, 4.083; 95% CI, 2.408-6.772, P<0.001), and cancer antigen 19-9 greater than or equal to 100 (hazard ratio, 2.058; 95% CI, 1.247-3.395, P=0.005) were identified as adverse prognostic factors in resected invasive IPMN. Conclusion: The current AT strategy may not be recommended to be performed with resected invasive IPMN in stage I and II groups, unlike pancreatic ductal adenocarcinoma. Further investigations of the potential role of AT in invasive IPMN are recommended. [ABSTRACT FROM AUTHOR]