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Since 2000 the Korean art world has witnessed the emergence of a new generation of artists. Arriving after the social and political upheavals of modern Korean society, this generation enjoys ready access to the larger world via the internet, ample opportunities to study/travel/work abroad, and broad recognition in international art fairs and exhibitions. Not surprisingly, unlike Korean artists of previous eras, their highly individual and varied works address ever more diverse issues in art, society and history. Their works do not conform to any overarching patterns, characteristics or attitudes that would point to ‘Korea’ as their common origin. What then makes them Korean artists? Do we suppose that their works deliver special insights about a unique culture and society, some definitive Korean-ness? Does it even matter whether we label their art ‘Korean’? By both exposing and questioning current discourse based in the transcendent ‘cult of origin’ of our seemingly globalized art world, this article will probe the possibilities of a ‘post-global’ paradigm in hopes of identifying a new path for arts discourse. [ABSTRACT FROM PUBLISHER]

Addressing the critical health concerns posed by domoic acid (DA), a neurotoxic compound produced by toxic marine algae and bioaccumulated in shellfish, necessitates the development of a rapid, precise, and robust detection system. Traditional DA detection methods have stability and sensitivity issues, which hinder effective toxin detection. To overcome these limitations, we developed a novel direct competitive enzyme-linked immunosorbent assay (dc-ELISA) platform that utilizes peptide-immobilized magnetic beads (MGBs/peptide). The affinity peptides identified through phage display and chemically synthesized with biotin labels present an innovative alternative to conventional antibodies for ELISA applications. Streptavidin-modified MGBs were used as the bioreceptor carriers to facilitate magnetic separation and simplify sample preparation, making the MGB/peptide-based dc-ELISA platform an ideal tool for comprehensive monitoring efforts. The developed platform exhibits a detection range of 0.5-10 ng mL -1 and a low limit of detection of 0.29 ng mL -1 , offering enhanced sensitivity and cost-effectiveness. Moreover, our developed dc-ELISA demonstrated a high recovery rate when validated with DA-spiked CRM-mussel samples. This method overcomes the limitations of traditional detection techniques and offers a scalable and efficient approach to marine toxin surveillance with improved marine environmental monitoring and public health management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Graphitic carbon nitride (g-C 3 N 4 ) has garnered much attention as a promising 2D material in the realm of electrochemical sensors. It contains a polymeric matrix that can serve as an economical and non-toxic electrode material for the detection of a diverse range of analytes. However, its performance is impeded by a relatively limited active surface area and inherent instability. Although electrochemistry involving metal-doped g-C 3 N 4 nanomaterials is rapidly progressing, it remains relatively unexplored. The metal doping of g-C 3 N 4 augments the electrochemically active surface area of the resulting electrode, which has the potential to significantly enhance electrode kinetics and bolster catalytic activity. Consequentially, the main objective of this review is to provide insight into the intricacies of synthesizing and characterizing metal-doped g-C 3 N 4 . Furthermore, we comprehensively delve into the fundamental attributes of electrochemical sensors based on metal-doped g-C 3 N 4 , with a specific focus on healthcare and environmental applications. These applications encompass a meticulous exploration of detecting biomolecules, drug molecules, and organic pollutants., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that may have influenced the work reported in this study., (Copyright © 2024. Published by Elsevier B.V.)

Saxitoxin (STX), which is produced by certain dinoflagellate species, is a type of paralytic shellfish poisoning toxin that poses a serious threat to human health and the environment. Therefore, developing a technology for the convenient and cost-effective detection of STX is imperative. In this study, we developed an affinity peptide-imprinted polymer-based indirect competitive ELISA (ic-ELISA) without using enzyme-toxin conjugates. AuNP/Co 3 O 4 @Mg/Al cLDH was synthesized by calcining AuNP/ZIF-67@Mg/Al LDH, which was obtained by combining AuNPs, ZIF-67, and flower-like Mg/Al LDH. This synthesized nanozyme exhibited high catalytic activity (K m  = 0.24 mM for TMB and 132.5 mM for H 2 O 2 ). The affinity peptide-imprinted polymer (MIP) was imprinted with an STX-specific template peptide (STX MIP) on a multi-well microplate and then reacted with an STX-specific signal peptide (STX SP). The interaction between the STX SP and MIP was detected using a streptavidin-coated nanozyme (SA-AuNP/Co 3 O 4 @Mg/Al cLDH). The developed MIP-based ic-ELISA exhibited excellent selectivity and sensitivity, with a limit of detection of 3.17 ng/mL (equivalent: 0.317 μg/g). Furthermore, the system was validated using a commercial ELISA kit and mussel tissue samples, and it demonstrated a high STX recovery with a low coefficient of variation. These results imply that the developed ic-ELISA can be used to detect STX in real samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We develop color-encoded multicompartmental hydrogel (MH) microspheres tailored for multiplexed bioassays using a drop-based microfluidic approach. Our method involves the creation of triple emulsion drops that feature thin sacrificial oil layers separating two prepolymer phases. This configuration leads to the formation of poly(ethylene glycol) (PEG) multi-compartmental core-shell microspheres through photopolymerization, followed by the removal of the thin oil layers. The core compartments stably incorporate pigments, ensuring their retention within the hydrogel network without leakage, which facilitates reliable color encoding across varying spatial positions. Additionally, we introduce small molecule fluorescent labeling into the chemically functionalized shell compartments, achieving consistent distribution of functional components without the core's contamination. Importantly, our integrated one-pot conjugation of these color-encoded microspheres with affinity peptides enables the highly sensitive and selective detection of influenza virus antigens using a fluorescence bioassay, resulting in an especially low detection limit of 0.18 nM and 0.66 nM for influenza virus H1N1 and H5N1 antigens, respectively. This approach not only highlights the potential of our microspheres in clinical diagnostics but also paves the way for their application in a wide range of multiplexed assays., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ultrathin molecularly imprinted polymer (MIP) films were deposited on the surfaces of ZnO nanorods (ZNRs) and nanosheets (ZNSs) by electropolymerization to afford extended-gate field-effect transistor sensors for detecting phenytoin (PHT) in plasma. Molecular imprinting efficiency was optimized by controlling the contents of functional monomers and the template in the precursor solution. PHT sensing was performed in plasma solutions with various concentrations by monitoring the drain current as a function of drain voltage under an applied gate voltage of 1.5 V. The reliability and reproducibility of the fabricated sensors were evaluated through a solution treatment process for complete PHT removal and PHT adsorption-removal cycling, while selectivity was examined by analyzing responses to chemicals with structures analogous to that of PHT. Compared with the ZNS/extracted-MIP sensor and sensors with non-imprinted polymer (NIP) films, the ZNR/extracted-MIP sensor showed superior responses to PHT-containing plasma due to selective PHT adsorption, achieving an imprinting factor of 4.23, detection limit of 12.9 ng/mL, quantitation limit of 53.0 ng/mL, and selectivity coefficients of 3-4 (against tramadol) and ~ 5 (against diphenhydramine). Therefore, we believe that the MIP-based ZNR sensing platform is promising for the practical detection of PHT and other drugs and evaluation of their proper dosages., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

This paper reports the development of a highly sensitive and selective electrochemical peptide-based biosensor for the detection of the inflammatory disease biomarker, interleukin-1beta (IL-1β). To this end, flower-like Au-Ag@MoS 2 -rGO nanocomposites were used as the signal amplification platform to achieve a label-free biosensor with a high sensitivity and selectivity. First, a high-affinity peptide for IL-1β was identified through biopanning with M13 random peptide libraries, and was newly designed by incorporating cysteine at the C-terminus. An IL-1β specific binding peptide was used as the bio-receptor, and the interaction between the IL-1β binding peptide and IL-1β was confirmed via enzyme-linked immunosorbent assay and various physicochemical and electrochemical analyses. Under optimal conditions, the biosensor achieved an ultrasensitive and specific IL-1β detection in a wide linear concentration range of 0-250 ng/mL with a picomolar-level detection limit (∼2.4 pM), low binding constant (∼0.62 pM), and a low coefficient of variation (<1.65 %). The biosensor was successfully utilized for IL-1β determination in the serum of Crohn's disease patients with a good correlation coefficient. In addition, the detection performance was comparable to that of commercially available IL-1β ELISA kit. This indicates that the electrochemical peptide-based biosensor may offer a potentially valuable platform for the clinical diagnosis of various inflammatory disease biomarkers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

There are limited data on outcomes after implantation of everolimus-eluting stents (EES) in East Asian patients with small vessel coronary lesions. A total of 1,600 patients treated with XIENCE EES (Abbott Vascular, CA, USA) were divided into the small vessel group treated with one ≤2.5 mm stent (n=119) and the non-small vessel group treated with one ≥2.75 mm stent (n=933). The primary end point was a patient-oriented composite outcome (POCO), a composite of all-cause death, myocardial infarction (MI), and any repeat revascularization at 12 months. The key secondary end point was a device-oriented composite outcome (DOCO), a composite of cardiovascular death, target-vessel MI, and target lesion revascularization at 12 months. The small vessel group was more often female, hypertensive, less likely to present with ST-elevation MI, and more often treated for the left circumflex artery, whereas the non-small vessel group more often had type B2/C lesions, underwent intravascular ultrasound, and received unfractionated heparin. In the propensity matched cohort, the mean stent diameter was 2.5±0.0 mm and 3.1±0.4 mm in the small and non-small vessel groups, respectively. Propensity-adjusted POCO at 12 months was 6.0% in the small vessel group and 4.3% in the non-small vessel group (p=0.558). There was no significant difference in DOCO at 12 months (small vessel group: 4.3% and non-small vessel group: 1.7%, p=0.270). Outcomes of XIENCE EES for small vessel disease were comparable to those for non-small vessel disease at 12-month clinical follow-up in real-world Korean patients., Competing Interests: CONFLICT OF INTEREST STATEMENT: None declared., (© Chonnam Medical Journal, 2024.)

Saxitoxin (STX) is a highly toxic small-molecule cyanotoxin that is water-soluble, stable in acidic media, and thermostable. STX is hazardous to human health and the environment in ocean, thus it is an important to detect it at very low concentrations. Herein, we developed an electrochemical peptide-based biosensor for the trace detection of STX in different sample matrix utilizing differential pulse voltammetry (DPV) signal. We synthesized the nanocomposite of zeolitic imidazolate framework-67 (ZIF-67) decorated bimetallic platinum (Pt) and ruthenium (Ru) nanoparticles (Pt-Ru@C/ZIF-67) using impregnation method. The nanocomposite modified with screen-printed electrode (SPE) was subsequently used to detect STX in the range of 1-1,000 ng mL -1 , with a detection limit (LOD) of 26.7 pg mL -1 . The developed peptide-based biosensor is highly selective and sensitive towards STX detection, thus it represents a promising strategy for the development of novel portable bioassay for monitoring various hazardous molecules in aquatic food chains., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Influenza viruses are known to cause pandemic flu outbreaks through both inter-human and animal-to-human transmissions. Therefore, the rapid and accurate detection of such pathogenic viruses is crucial for effective pandemic control. Here, we introduce a novel sensor based on affinity peptide-immobilized hydrogel microspheres for the selective detection of influenza A virus (IAV) H3N2. To enhance the binding affinity performance, we identified novel affinity peptides using phage display and further optimized their design. The functional hydrogel microspheres were constructed using the drop microfluidic technique, employing a structure composed of natural (chitosan) and synthetic (poly(ethylene glycol) diacrylate and PEG 6 kDa) polymers with the activation of azadibenzocyclooctyne for the subsequent click chemistry reaction. The binding peptide-immobilized hydrogel microsphere (BP-Hyd) was characterized by field emission scanning electron microscopy, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy and exhibited selective detection capability for the IAV H3N2. To capture the detected IAV H3N2, a Cy3-labeled IAV hemagglutinin antibody was utilized. By incorporating the affinity peptide with hydrogel microspheres, we achieved quantitative and selective detection of IAV H3N2 with a detection limit of 1.887 PFU mL -1 . Furthermore, the developed suspension sensor exhibited excellent reproducibility and showed reusability potential. Our results revealed that the BP-Hyd-based fluorescence sensor platform could be feasibly employed to detect other pathogens because the virus-binding peptides can be easily replaced with other peptides through phage display, enabling selective and sensitive binding to different targets.

Okadaic acid (OA) is a type of marine biotoxin produced by some species of dinoflagellates in marine environments. Consumption of shellfish contaminated with OA can cause diarrhetic shellfish poisoning (DSP) in humans with symptoms that typically include abdominal pain, diarrhea and vomiting. In this study, we developed an affinity peptide-based direct competition enzyme-linked immunosorbent assay (dc-ELISA) for the detection of OA in real samples. The OA-specific peptide was successfully identified via M13 biopanning and a series of peptides were chemically synthesized and characterized their recognition activities. The dc-ELISA system showed good sensitivity and selectivity with a half-maximal inhibitory concentration (IC 50 ) of 148.7 ng/mL and a limit of detection (LOD) of 5.41 ng/mL (equivalent, 21.52 ng/g). Moreover, the effectiveness of the developed dc-ELISA was validated using OA-spiked shellfish samples, and the developed dc-ELISA showed a high recovery rate. These results suggest that the affinity peptide-based dc-ELISA can be a promising tool for detecting OA in shellfish samples., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

C-reactive protein (CRP) is a phylogenetically highly conserved plasma protein found in blood serum, and an enhanced CRP level is indicative of inflammatory conditions such as infection and cancer, among others. In this work, we developed a novel high CRP-affinity peptide-functionalized label-free electrochemical biosensor for the highly sensitive and selective detection of CRP. Throughout biopanning with random peptide libraries, high affinity peptides for CRP was successfully identified, and then a series of synthetic peptide receptor, of which C-terminus was incorporated to gold binding peptide (GBP) as an anchoring motif was covalently immobilized onto gold nanoparticle (AuNPs) tethered polydopamine (PDA)‒black phosphorus (BP) (AuNPs@BP@PDA) nanocomposite electrode. Interaction between the CRP-binding peptide and CRP was confirmed via enzyme-linked immunosorbent assay along with various physicochemical and electrochemical analyses. Under the optimized experimental conditions, the proposed peptide-based biosensor detects CRP in the range of 0-0.036 μg/mL with a detection limit (LOD) of 0.7 ng/mL. The developed sensor effectively detects CRP in the real samples of serum and plasma of Crohn's disease patients. Thus, the fabricated peptide-based biosensor has potential applications in clinical diagnosis and medical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Calcified coronary lesions can cause stent under-expansion, malapposition, and polymer degradation, hence increasing the risk of adverse clinical outcomes. Percutaneous coronary intervention (PCI) guided by intravascular ultrasound (IVUS) has been used regularly to improve outcomes. Our primary aim was to evaluate the clinical efficacy of IVUS-guided PCI in calcified coronary lesions., Methods: From August 2018 to December 2021, we prospectively included 300 patients in the CAPIRO study (CAlcified plaque in patients receiving Resolute Onyx ® ) at three educational hospitals in Jeonbuk Province. We studied 243 patients (265 lesions) who were followed up for over a year. Based on coronary calcification by IVUS analysis, the patient population was categorized into two groups (Group I: non/mild calcification; Group II: moderate/severe calcification (maximum calcium arc >180° and calcium length > 5 mm)). One-to-one Propensity Score Matching was used to match the baseline characteristics. The stent expansion rate was analyzed by recent criteria. The primary clinical outcome was Major Adverse Cardiac Events (MACE), which included Cardiac death, Myocardial Infarction (MI), and Target Lesion Revascularization (TLR)., Results: After follow-up time, the MACE rate in Group I was 1.99%, comparable to Group II's 1.09% ( p = 0.594). The components of MACE did not significantly differ between the two groups. Based on absolute MSA or MSA/MVA at MSA site criteria, the stent expansion rate in Group II was lower than that of Group I. Nevertheless, based on recent relative criteria, the stent expansion rate in both groups was comparable., Conclusions: After more than a year of follow-up, IVUS-guided PCI in moderate/severe calcification lesions was associated with good clinical outcomes, which was comparable with non/mild calcification lesions. Future studies with a larger sample size and a more extended follow-up period are required to clarify our findings.

Influenza viruses are known to cause pandemic flu through inter-human and animal-to-human transmissions. Neuraminidase (NA), which is a surface glycoprotein of both influenza A and B viruses, is a minor immunogenic determinant; however, it has been proposed as an ideal candidate for a real testing. We successfully identified an affinity peptide which is specific to the influenza H5N1 virus NA via phage display technique and observed initially its binding affinities using enzyme-linked immunosorbent assay (ELISA). In addition, four synthetic peptides were chemically synthesized to develop an affinity peptide-based electrochemical biosensing system. Among all peptides tested, INA BP2 was selected as a potential candidate and subjected to square-wave voltammetry (SWV) for evaluating their detection performance. To enhance analytical performance, a three-dimensional porous bovine serum albumin (BSA)-MXene (BSA/MXene) matrix was applied. The surface morphology of the BSA/MXene film-deposited electrode was analyzed using X-ray photoelectron spectroscopy (XPS), field-emission scanning electron microscopy (FE-SEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Using SWV measurement, the BSA/MXene nanocomposite-based peptide sensor exhibited significant the dissociation constant (K d  = 9.34 ± 1.20 nM) and the limit of detection (LOD, 0.098 nM), resulting in good reproducibility, stability and recovery, even in the presence with spiked human plasma. These results demonstrate an alternative way of new bioanalytical sensing platform for developing more desirable sensitivity in other virus detection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The lethality of the bovine viral diarrhea virus (BVDV) in cattle involves inapparent infection and various, typically subclinical, syndromes. Cattle of all ages are vulnerable to infection with the virus. It also causes considerable economic losses, primarily due to reduced reproductive performance. In the absence of treatment that can completely cure infected animals, detection of BVDV relies on highly sensitive and selective diagnosis methods. In this study, an electrochemical detection system was developed as a useful and sensitive system for the detection of BVDV to suggest the direction of diagnostic technology through the development of conductive nanoparticle synthesis. As a countermeasure, a more sensitive and rapid BVDV detection system was developed using the synthesis of electroconductive nanomaterials black phosphorus (BP) and gold nanoparticle (AuNP). To increase the conductivity effect, AuNP was synthesized on the BP surface, and the stability of BP was improved by using dopamine self-polymerization. Moreover, its characterizations, electrical conductivity, selectivity, and sensitivity toward BVDV also have been investigated. The BP@AuNP-peptide-based BVDV electrochemical sensor exhibited a low detection limit of 0.59 copies mL -1 with high selectivity and long-term stability (retaining 95% of its initial performance over 30 days).

Here, we report PNIPAm-co-PEGDA hydrogel shelled microcapsules with a thin oil layer to achieve tunable thermo-responsive release of the encapsulated small hydrophilic actives. We use a microfluidic device integrated with a temperature-controlled chamber for consistent and reliable production of the microcapsules by utilizing triple emulsion drops (W/O/W/O) with a thin oil layer as capsule templates. The interstitial oil layer between the aqueous core and the PNIPAm-co-PEGDA shell provides a diffusion barrier for the encapsulated active until the temperature reaches a critical point above which the destabilization of interstitial oil layer occurs. We find that the destabilization of the oil layer with temperature increase is caused by outward expansion of the aqueous core due to volume increase and the radial inward compression from the deswelling of the thermo-responsive hydrogel shell. The copolymerization of NIPAm with PEGDA increases the biocompatibility of the resulting microcapsule while offering the ability to alter the compressive modulus in broad ranges by simply varying crosslinker concentrations thereby to precisely tune the onset release temperature. Based on this concept, we further demonstrate that the release temperature can be enhanced up to 62 °C by adjusting the shell thickness even without varying the chemical composition of the hydrogel shell. Moreover, we incorporate gold nanorods within the hydrogel shell to spatiotemporally regulate the active release from the microcapsules by illuminating with non-invasive near infrared (NIR) light., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Cathepsin B, a cysteine protease, is considered a potential biomarker for early diagnosis of cancer and inflammatory bowel diseases. Therefore, more feasible and effective diagnostic method may be beneficial for monitoring of cancer or related diseases., Results: A phage-display library was biopanned against biotinylated cathepsin B to identify a high-affinity peptide with the sequence WDMWPSMDWKAE. The identified peptide-displaying phage clones and phage-free synthetic peptides were characterized using enzyme-linked immunosorbent assays (ELISAs) and electrochemical analyses (impedance spectroscopy, cyclic voltammetry, and square wave voltammetry). Feasibilities of phage-on-a-sensor, peptide-on-a-sensor, and peptide-on-a-AuNPs/MXene sensor were evaluated. The limit of detection and binding affinity values of the peptide-on-a-AuNPs/MXene sensor interface were two to four times lower than those of the two other sensors, indicating that the peptide-on-a-AuNPs/MXene sensor is more specific for cathepsin B (good recovery (86-102%) and %RSD (< 11%) with clinical samples, and can distinguish different stages of Crohn's disease. Furthermore, the concentration of cathepsin B measured by our sensor showed a good correlation with those estimated by the commercially available ELISA kit., Conclusion: In summary, screening and rational design of high-affinity peptides specific to cathepsin B for developing peptide-based electrochemical biosensors is reported for the first time. This study could promote the development of alternative antibody-free detection methods for clinical assays to test inflammatory bowel disease and other diseases., (© 2023. The Author(s).)

The COVID-19 pandemic and the resulting supply chain disruption have rekindled crucial needs for safe storage and transportation of essential items. Despite recent advances, existing temperature monitoring technologies for cold chain management fall short in reliability, cost, and flexibility toward customized cold chain management for various products with different required temperature. In this work, we report a novel capsule-based colorimetric temperature monitoring system with precise and readily tunable temperature ranges. Triple emulsion drop-based microfluidic technique enables rapid production of monodisperse microcapsules with an interstitial phase-change oil (PCO) layer with precise control over its dimension and composition. Liquid-solid phase transition of the PCO layer below its freezing point triggers the release of the encapsulated payload yielding drastic change in color, allowing user-friendly visual monitoring in a highly sensitive manner. Simple tuning of the PCO layer's compositions can further broaden the temperature range in a precisely controlled manner. The proposed simple scheme can readily be formulated to detect both temperature rise in the frozen environment and freeze detection as well as multiple temperature monitoring. Combined, these results support a significant step forward for the development of customizable colorimetric monitoring of a broad range of temperatures with precision., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Elsevier B.V. All rights reserved.)

Introduction: We highlight the utility of telemedicine and telementoring for the management of orthopaedic emergencies using a case of forearm compartment syndrome following a penetrating trauma in a northern Inuit community in Nunavik, Quebec, Canada., Methods & Results: As in many cases of compartment syndrome in rural settings, the patient was at a high risk of developing irreversible complications. A prompt diagnosis followed by an emergency decompressive fasciotomy was warranted. Using telemedicine and telementoring guidance, the diagnosis of compartment syndrome was made, and the patient's volar compartment was successfully decompressed by a local emergency physician in a timely manner. Subsequently, the patient was able to be safely transferred to a level 1 trauma centre for further surgical management. This included a second-look operative exploration, irrigation and debridement, completion of volar fasciotomy and ulnar nerve decompression. No complications were seen., Discussion: Our experience highlights two important clinical implications. First, telemedicine can be successfully implemented to facilitate clinical diagnosis of surgical emergencies in the rural setting. Second, telementoring can effectively allow surgeons to guide physicians remotely to perform emergency decompressive fasciotomy, which can help salvage the affected limb and significantly decrease the risk of debilitating complications.

Background: Juvenile hallux valgus (JHV) is a forefoot deformity that causes pain and functional limitation. Treatment poses a challenge in terms of the optimal technique and timing of intervention. A systematic review of the literature on the use of growth modulation in treating JHV was conducted., Materials and Methods: The literature review was performed using PubMed and EMBASE searches for articles investigating growth modulation in the treatment of JHV published before December 1st, 2021. Seven articles were included in the final review that matched the inclusion and exclusion criteria. The primary outcomes included the degree of correction of hallux valgus angle and intermetatarsal angle. A qualitative assessment of the articles was done due to the heterogeneity of the growth modulation methods used in these articles., Results: A total of 135 feet from 78 patients were included from the reviewed articles. Growth modulation methods included temporary screw lateral hemiepiphysiodesis of the first metatarsal, lateral drilling hemiepiphysiodesis of the first metatarsal, and a trephine plug removal of the lateral epiphysis followed by cancellous bone graft insertion. The degree of correction of the hallux valgus and intermetatarsal angles were found to be statistically significant in all studies, regardless of the technique., Conclusion: Growth modulation for JHV by lateral hemiepiphysiodesis using minimally invasive techniques produced favourable radiologic outcomes with some evidence of clinical improvement. Larger, prospective and comparative studies with objective clinical outcome measures may further consolidate this surgical approach as a mean to treating this deformity., How to Cite This Article: AlZeedi M, Park JP, Marwan Y, et al . Growth Modulation for the Treatment of Juvenile Hallux Valgus: A Systematic Review of Literature. Strategies Trauma Limb Reconstr 2023;18(1):51-55., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2023; The Author(s).)

Glutathione, a tripeptide consisting of cysteine, glutamic acid, and glycine, has multiple beneficial effects on human health. Previous studies have focused on producing glutathione in Saccharomyces cerevisiae by overexpressing γ-glutamylcysteine synthetase (GSH1) and glutathione synthetase (GSH2), which are the rate-limiting enzymes involved in the glutathione biosynthetic pathway. However, the production yield and titer of glutathione remain low due to the feedback inhibition on GSH1. To overcome this limitation, a synthetic isozyme system consisting of a novel bifunctional enzyme (GshF) from Gram-positive bacteria possessing both GSH1 and GSH2 activities, in addition to GSH1/GSH2, was introduced into S. cerevisiae, as GshF is insensitive to feedback inhibition. Given the HSP60 chaperonin system mismatch between bacteria and S. cerevisiae, co-expression of Group-I HSP60 chaperonins (GroEL and GroES) from Escherichia coli was required for functional expression of GshF. Among various strains constructed in this study, the SKSC222 strain capable of synthesizing glutathione with the synthetic isozyme system produced 240 mg L -1 glutathione with glutathione content and yield of 4.3% and 25.6 mg glutathione /g glucose , respectively. These values were 6.6-, 4.9-, and 4.3-fold higher than the corresponding values of the wild-type strain. In a glucose-limited fed-batch fermentation, the SKSC222 strain produced 2.0 g L -1 glutathione in 67 h. Therefore, this study highlights the benefits of the synthetic isozyme system in enhancing the production titer and yield of value-added chemicals by engineered strains of S. cerevisiae., (© 2022 Wiley-VCH GmbH.)

The potential for pharmacodynamic (PD) biomarkers to improve the efficiency of biosimilar product development and regulatory approval formed the premise for the virtual workshop Pharmacodynamic Biomarkers for Biosimilar Development and Approval hosted by the US Food and Drug Administration (FDA) and Duke Margolis, September 2021. Although the possibility of PD biomarkers replacing the to-date routine comparative phase III confirmatory study currently expected by the FDA was discussed, the motivation and feasibility for biosimilar sponsors developing such markers and the regulatory risks entailed largely were not. Even more fundamental is the already established greater comparative value of the pharmacokinetic (PK) study as the most sensitive clinical assay for detecting subtle differences between two products. Consequently, the comparative analytical assessment and the head-to-head PKs will have already answered the core questions as to the biosimilarity of the candidate product to its reference. No further actionable information is obtained with either a PD study or a comparative clinical phase III study even as they may provide some reassurance of what is already known. When a suitable PD biomarker is available for the originator reference product they have already been used for biosimilar development. We must carefully consider the core requirements and timelines inherent in biosimilar development and how they occur in parallel rather than in the series we see for originator products. In order to improve the efficiency of biosimilar development, we need to ask the right questions based on a full understanding of how biosimilars have been developed to date and can be in the future., (© 2022 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Patellofemoral instability (PFI) is a prevalent cause of knee pain and disability. It affects mostly young females with an incidence reported as high as 1 in 1,000. Risk factors for instability include trochlear dysplasia, patella alta, increased tibial tubercle-to-trochlear groove distance, abnormal patella lateral tilt, and coronal and torsional malalignment. Nonsurgical and surgical options for PFI can treat the underlying causes with varied success rates. The goal of this review series was to synthesize the current best practices into a concise, algorithmic approach. This article is the first in a two-part review on PFI, which focuses on the clinical and radiological evaluation, followed by nonsurgical management. The orthopaedic surgeon should be aware of the latest diagnostic protocol for PFI and its nonsurgical treatment options, their indications, and outcomes., (Copyright © 2022 by the American Academy of Orthopaedic Surgeons.)

Influenza viruses can cause epidemics through inter-human transmission, and the social consequences of viral transmission are incalculable. Current diagnostics for virus detection commonly relies on antibodies or nucleic acid as recognition reagent. However, a more advanced and general method for the facile development of new biosensors is increasing in demand. In this study, we report the fabrication of an ultra-sensitive peptide-based nanobiosensor using a nickel oxide (NiO)-reduced graphene oxide (rGO)/MXene nanocomposite to detect active influenza viruses (H1N1 and H5N2) and viral proteins. The sensing mechanism is based on the signal inhibition, the specific interaction between H1N1 (QMGFMTSPKHSV) and H5N1 (GHPHYNNPSLQL) binding peptides anchored on the NiO-rGO/MXene/glassy carbon electrode (GCE) surface and the viral surface protein hemagglutinin (HA) is the critical factor for the decrease in the peak current of the sensor. In this strategy, the NiO-rGO/MXene nanocomposite results in synergistic signal effects, including electrical conductivity, porosity, electroactive surface area, and active site availability when viruses are deposited on the electrode. Based on these observations, the results showed that the developed nanobiosensor was capable of highly sensitive and specific detection of their corresponding influenza viruses and viral proteins with a very low detection limit (3.63 nM of H1N1 and 2.39 nM for H5N1, respectively) and good recovery. The findings demonstrate that the proposed NiO-rGO/MXene-based peptide biosensor can provide insights for developing a wide range of clinical screening tools for detecting affected patients., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Identifying alternatives to antibodies as bioreceptors to test samples feasibly is crucial for developing next-generation in vitro diagnostic methods. Here, we aimed to devise an analytical method for detecting H1N1 viral proteins (hemagglutinin [HA] and neuraminidase [NA]) as well as the complete H1N1 virus with high sensitivity and selectivity. By applying biopanning of M13 peptide libraries, high affinity peptides specific for HA or NA were successfully identified. After selection, three different synthetic peptides that incorporated gold-binding motifs were designed and chemically synthesized on the basis of the original sequence identified phage display technique with or without two repeat. Their binding interactions were characterized by enzyme-linked immunosorbent assay (ELISA), square wave voltammetry (SWV), Time of flight-secondary ion mass spectroscopy (ToF-SIMS) and X-ray photoelectron spectroscopy (XPS). The binding constants (K d ) of HA BP1, HA BP2 and NA BP1 peptides were found to be 169.72 nM, 70.02 nM and 224.49 nM for HA or NA proteins by electrochemical measurements (SWV). The single use of HA BP2 peptide enabled the detection of either H1N1 viral proteins or the actual H1N1 virus, while NA BP1 peptide exhibited lower binding for real H1N1 virus particles. Moreover, the use of both HA BP1 and BP2 as a divalent capturing reagent improved sensor performance as well as the strength of the electrochemical signal, thereby exhibiting a dual synergistic effect for the electrochemical detection of H1N1 antigens with satisfactory specificity and sensitivity (limit of detection of 1.52 PFU/mL)., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Here, we report the existence of dural channels in the parasagittal dural space and dura mater in humans. Microscopic mapping was performed to observe dural channels and arachnoid granulations in the whole dural tissue of nine individuals, and ultrastructural examinations and 3D micro-CT were used for further identification. The dural channels were concentrated along the parasagittal dural space regardless of the distribution of arachnoid granulations. Microscopically, they varied in size, presenting as distorted round-shaped empty spaces resembling mature fat vacuoles without subcellular structures. We found them to be lacking in the expression of lymphatic and vascular markers. 3D micro-CT revealed Swiss-cheese-like structured empty spaces connected to each other. Our findings show that dural channels are part of the anatomical structure of the parasagittal dural and space and dura mater. Although they are not the meningeal lymphatic vessels themselves, dural channels may serve as a reservoir of cerebrospinal fluid drainage., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Biologics are increasingly vital medicines that significantly reduce morbidity as well as mortality, yet access continues to be an issue even in apparently wealthy countries, such as the USA. While patient access is expected to improve with the introduction of biosimilars, misperceptions in a significant part based on terminology continue to make a sustained contribution by biosimilars difficult. Patients are and will continue to suffer needlessly if biosimilars continue to be impugned. Consequently, it is increasingly urgent that semantics are clarified, and in particular, the implication that interchangeable biologics are better biosimilars dismissed. This paper distinguishes between the real differences between biologics that matter clinically to patients and discusses the actual meaning of a US Food and Drug Administration designation of interchangeability for a biosimilar product. This will help highlight where there is need for further Food and Drug Administration education and which stakeholders likely need that education the most., (© 2022. The Author(s).)

Background: Synovial chondromatosis (SC) of the shoulder is rare, with limited literature on its management. This systematic review of literature aimed to characterize common arthroscopic techniques for the treatment of shoulder SC and patient outcomes. We hypothesized that arthroscopy is an effective operative modality for the management of shoulder SC., Methods: PubMed and Embase databases were searched for articles on arthroscopic management of shoulder SC, published before 6 August 2020. All articles meeting inclusion criteria received an independent full-text review by two authors., Results: An initial search found 64 articles. Following duplicate removal and title, abstract, and full-text reviews, 27 articles (48 patients) remained eligible. The mean age of patients was 33.0 years, with 2:1 male-to-female ratio. The mean follow-up was 41.8 months. SC was found to affect various intra- and extra-articular locations of the shoulder. Overall, arthroscopic treatment of shoulder SC was successful in 70.8%. Treatment failure was common in SC involving the bicipital tendon sheath. Disease recurrence was seen in 14.7%., Conclusion: Literature on arthroscopic management of shoulder SC is limited, and significant heterogeneity in arthroscopic techniques was observed. Although arthroscopic management of shoulder SC is effective, further optimization is necessary to minimize treatment failure and disease recurrence., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2020 The British Elbow & Shoulder Society.)

Caspase-3, a cysteine-dependent protease, is considered a reliable molecular biomarker for the diagnosis and prognosis of apoptosis-related diseases. In this study, we demonstrated a phage-based electrochemical biosensor for the evaluation of cell apoptosis by the sensitive and specific detection of caspase-3. Specifically, for screening of affinity peptide-displayed phages, phage display was performed using M13 phage libraries (cyclic forms of peptides), and we identified potential affinity peptide-displayed phage clones with the sequence CPTTMWRYC. After characterization of its binding affinity using enzyme-linked immunosorbent assay, whole phage particles were covalently attached to a gold surface using coupling chemistry (MUA-EDC/NHS). The developed phage sensor was characterized by X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), scanning electron microscopy (SEM), electrochemical analysis using cyclic voltammetry (CV), and square wave voltammetry (SWV). Under optimal conditions, the affinity peptide-displayed phage sensor showed a good binding affinity (K d  = 0.13 ± 0.56 μM) and limit of detection (0.39 μM) for caspase-3 detection. Furthermore, developed phage sensor could be monitored the response of apoptotic HeLa cells by detecting caspase-3 activity. This work should stimulate the development of efficient alternative caspase-3 detection methods for the diagnosis and prognosis of apoptosis-related diseases., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Whole peptide-displayed phage particles are promising alternatives to antibodies in sensor development; however, greater control and functionalization of these particles are required. In this study, we aimed to identify and create highly sensitive and selective phage-based electrochemical biosensors for detecting ovomucoid, a known food allergen. Phage display was performed using two different phage libraries (cyclic and linear form of peptides), which displayed affinity peptides capable of binding specifically to ovomucoid. Throughout the biopanning, two phage clones that displayed both peptides (CTDKASSSC and WWQPYSSAPRWL) were selected. After the characterization of their binding affinities, both whole phage particles were covalently attached to a gold electrode using crosslinking chemistry (MUA-EDC/NHS and Sulfo-LC/SPDP); the developed phage sensor was characterized using cyclic voltammetry (CV), square wave voltammetry (SWV), and electrochemical impedance spectroscopy (EIS). The cyclic peptide-displayed phage sensor modified using EDC/NHS chemistry exhibited significantly better binding affinity (K d  = 2.36 ± 0.44 μg/mL) and limit of detection (LOD, 0.12 μg/mL) for ovomucoid than the linear phage sensor, resulting in good reproducibility and recovery, even in an actual egg and white wine samples. This approach may provide an alternative and more efficient way of sensing food allergens with desirable sensitivity, selectivity, and feasibility in food diagnostic applications., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Graphene is an intriguing two-dimensional honeycomb-like carbon material with a unique basal plane structure, charge carrier mobility, thermal conductivity, wide electrochemical spectrum, and unusual physicochemical properties. Therefore, it has attracted considerable scientific interest in the field of nanoscience and bionanotechnology. The high specific surface area of graphene allows it to support high biomolecule loading for good detection sensitivity. As such, graphene, graphene oxide (GO), and reduced GO are excellent materials for the fabrication of new nanocomposites and electrochemical sensors. Graphene has been widely used as a chemical building block and/or scaffold with various materials to create highly sensitive and selective electrochemical sensing microdevices. Over the past decade, significant advancements have been made by utilizing graphene and graphene-based nanocomposites to design electrochemical sensors with enhanced analytical performance. This review focus on the synthetic strategies, as well as the structure-to-function studies of graphene, electrochemistry, novel multi nanocomposites combining graphene, limit of detection, stability, sensitivity, assay time. Finally, the review describes the challenges, strategies and outlook on the future development of graphene sensors technology that would be usable for the internet of things are also highlighted., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Allergy-causing inflammatory diseases have attracted significant attention because they have emerged as global health problems linked to urbanization. Interleukin-33 (IL-33) plays an important role in producing inflammatory cytokines, and it has been suggested as a target for the diagnosis and treatment of allergy-causing inflammatory diseases. In this work, specific peptides that bind to IL-33 were identified by a phage display technique and their molecular interactions were described. The peptide-displaying phages were selected on the basis of relative binding affinity by using enzyme-linked immunosorbent assay (ELISA) and square wave voltammetry (SWV). The selected IL-33 specific peptide was identified as FGLEPRANLHFT. To investigate the molecular interactions between IL-33 and the affinity peptide, the peptide was separated from the phage particles, chemically synthesized and characterized by SWV, isothermal titration calorimetry (ITC), and microscale thermophoresis (MST). The binding constant (K d ) value with SWV, MST, and ITC was found to be 1.68 ± 0.37 μM, 5.98 ± 1.30 μM, and 2.68 ± 1.37 μM, respectively. Two-dimensional (2D) NMR spectral analysis was performed to elucidate the primary peptide binding site of IL-33, which was near the ST2-D3 and IL1RAcP-D3 binding interfaces. Based on these observations using two different approaches, we conclude that this approach could be applied not only for the design of new peptides or peptide biomimetics for drug development, but also for the creation of unique molecular recognition elements useful for allergy diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Aim: Difucosyllactose (Di-FL) has strong antimicrobial activity against various pathogens, including group B Streptococcus, identified as the leading cause of neonatal sepsis. In this study, we sought to develop Escherichia coli as a microbial cell factory for efficiently producing Di-FL as well as 2'-fucosyllactose (2'-FL), the most abundant fucosylated oligosaccharide in human milk, by utilizing the salvage guanosine 5'-diphosphate (GDP)-l-fucose biosynthetic pathway., Main Methods and Major Results: The biosynthetic pathway for producing fucosylated oligosaccharides via the salvage pathway requires two enzymes, l-fucokinase/GDP-l-fucose phosphorylase (FKP) from Bacteroides fragilis and α-1,2-fucosyltransferase (FucT2) from Helicobacter pylori. To decrease the intracellular accumulation of 2'-FL while increasing substrate accessibility to FKP and FucT2, we evaluated whether extracellular secretion of FKP and FucT2 would enhance the production of fucosylated oligosaccharides. Among various engineered strains constructed in this study, the ΔLFAR-YA/FF+P-PLA 2 strain expressing phospholipase A 2 (PLA 2 ) from Streptomyces violaceoruber, whose native signal peptide was replaced with the PelB signal peptide (P-PLA 2 ), could secrete both FKP and FucT2 into the culture medium. Notably, it was observed that FKP and FucT2 present in the extracellular fraction could catalyze the synthesis of Di-FL from lactose and fucose. As a result, a batch fermentation with the ΔLFAR-YA/FF+P-PLA 2 strain resulted in the production of 1.22 ± 0.01 g L -1 Di-FL and 0.47 ± 0.01 g L -1 2'-FL, whereas the control strain could only produce 0.65 ± 0.01 g L -1 2'-FL., Conclusions and Implications: This study highlights the benefits of extracellular secretion of enzymes to improve biotransformation efficiency, as the transport of substrates and/or products across the cell membrane is limited., (© 2022 Wiley-VCH GmbH.)

Food allergies are abnormal immune responses that typically occur within short period after exposure of certain allergenic proteins in food or food-related resources. Currently, the means to treat food allergies is not clearly understood, and the only known prevention method is avoiding the consumption of allergen-containing foods. From the viewpoint of analytical methods, the effective detection of food allergens is hindered by the effects of various treatment processes and food matrices on trace amounts of allergens. The aim of this effort is to provide the reader with a clear and concise view of new advances for the detection of food allergens. Therefore, the present review explored the development status of various biosensors for the real-time, on-site detection of food allergens with high selectivity and sensitivity. The review also described the analytical consideration for the quantification of food allergens, and global development trends and the future availability of these technologies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In nature, individual cells are compartmentalized by a membrane that protects the cellular elements from the surrounding environment while simultaneously equipped with an antioxidant defense system to alleviate the oxidative stress resulting from light, oxygen, moisture, and temperature. However, this mechanism has not been realized in cellular mimics to effectively encapsulate and retain highly reactive antioxidants. Here, we report cell-inspired hydrogel microcapsules with an interstitial oil layer prepared by utilizing triple emulsion drops as templates to achieve enhanced retention of antioxidants. We employ ionic gelation for the hydrogel shell to prevent exposure of the encapsulated antioxidants to free radicals typically generated during photopolymerization. The interstitial oil layer in the microcapsule serves as an stimulus-responsive diffusion barrier, enabling efficient encapsulation and retention of antioxidants by providing an adequate pH microenvironment until osmotic pressure is applied to release the cargo on-demand. Moreover, addition of a lipophilic reducing agent in the oil layer induces a complementary reaction with the antioxidant, similar to the nonenzymatic antioxidant defense system in cells, leading to enhanced retention of the antioxidant activity. Furthermore, we show the complete recovery and even further enhancement in antioxidant activity by lowering the storage temperature, which decreases the oxidation rate while retaining the complementary reaction with the lipophilic reducing agent.

Bovine diarrhea is a major concern in the global bovine industry because it can cause significant financial damage. Of the many potential infectious agents that can lead to bovine diarrhea, bovine rotavirus (BRV) is a particular problem due to its high transmissibility and infectivity. Therefore, it is important to prevent the proliferation of BRV using an early detection system. This study developed an affinity peptide-based electrochemical method for use as a rapid detection system for BRV. A BRV-specific peptide was identified via the phage display technique and chemically synthesized. The synthetic peptide was immobilized on a gold electrode through thiol-gold interactions. The performance of the BRV specific binding peptides was evaluated using square wave voltammetry. The developed detection system exhibited a low detection limit (5 copies/mL) and limit of quantitation (2.14 × 10 2 copies/mL), indicating that it is a promising sensor platform for the monitoring of BRV., Competing Interests: The authors declare no conflict of interest., (© The Korean Society for Biotechnology and Bioengineering and Springer 2022.)

Herein, we describe a high-performance electrochemical sensor for the detection of regorafenib (REG) using bimetallic Pd-Ru nanoparticles anchored on pomegranate peel extract (PPE) derived reduced graphene oxide (Pd-Ru/rGO). PPE was employed to neutralize the extremely acidic graphene then cast-off along with the metal precursor for the duration of the chemical reduction to accomplish well dispersed Pd-Ru nanoparticles. Bimetallic Pd-Ru/rGO nanocomposites were synthesized using a facile chemical reduction method. Under optimal conditions, based on the differential pulse voltammetric studies it has been confirmed that the fabricated sensors has good electrocatalytic activity toward the detection of REG, spanning over the linear dynamic range of 0.5-300 nM. Moreover, the sensor exhibited a low limit of detection of 1.6 nM and a limit of quantification of 4.8 nM. The electrochemical sensor unveiled admirable selectivity and sensitivity, reproducibility, and repeatability. The fabricated sensor was suitable for real sample analysis (pharmaceutical tablet, human blood plasm, wastewater) with satisfactory recovery. The strategy presented herein can be employed in the development of electrochemical sensors for other target analytes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Although it is one of the core cultural values of Asian American families and an influential determinant of youth development, familism remains under-studied among Asian Americans and, despite crucial within-group heterogeneity, lacks subgroup specificity. This study describes the ways in which two major Asian American subgroups of youth, i.e., Filipino Americans and Korean Americans, maintain traditional familism. Specifically, this study constructed six self-report subscales of familism utilizing underused and new survey items and tested their psychometric properties. Using data collected from Filipino American ( n =150) and Korean American ( n =188) adolescents living in a Midwest metropolitan area, the measures were examined for validity and reliability for each group and, when appropriate, for measurement invariance across the groups. The main findings are that the finalized scales demonstrated solid reliability and validity (e.g., content and construct) in each group and some invariance and that core traditions, in the form of familism values and behaviors, persevere among second-generation Asian Americans, although familism was more evident among Filipino American youth than in Korean American youth. In both groups, subdomains of familism were not as discrete as found among their parents, who were predominantly foreign-born first-generation immigrants. The finalized familism scales were associated differently with several correlates including acculturation variables and youth outcomes. The findings are discussed with a call for further empirical research of diverse ethnic groups and immigrant generations to more accurately account for how family process interacts with cultural origin and acculturation., Competing Interests: Conflicts of Interest The authors report no conflict of interests.

Expression of aberrant microRNA (miRNA) is associated with tumour formation, migration, and invasion. However, there is limited information about the epigenetics of pituitary tumorigenesis. This study investigated the role of miRNA expression during the tumorigenesis of growth hormone (GH)-secreting pituitary tumours. miRNA profiling and real-time PCR were used to analyse the mRNA expression profile in sequential pituitary tissues of a unique animal model with a GH-producing pituitary tumour. Selected miRNAs were further validated in GH-producing cell lines and human pituitary tumour samples. The expression of significantly altered miRNAs and their predicted targets, as detected by microarray, was evaluated by real-time PCR, Western blotting, and immunohistochemistry using samples from mouse models and human pituitary tumours. The effect of miRNAs on tumour proliferation and invasion was examined in GH3 cells using the MTS and Matrigel invasion assays. Among the 14 miRNAs whose expression was significantly changed, miR-216a-5p (fold change = -5.638, P -value = 0.014) and miR-652-3p (fold change = -3.482, P -value = 0.010) were constantly and significantly downregulated. Transfection with mimics of miR-216a-5p and miR-652-3p inhibited GH3 proliferation and invasion, whereas inhibitors promoted them. The direct target genes of miR-216a-5p and miR-652-3p were Jak2 and Prrx1, respectively, which were downregulated in GH3 cells transfected with mimics and in serial pituitary gland tissues, including hyperplasic tissues and tumours of acromegalic animal models and pituitary tumour tissues of acromegalic patients. Downregulated miR-216a-5p and miR-652-3p expression may contribute to tumour progression by targeting JAK2 and PRRX1 on GH-producing pituitary tumours.

Objective: The mechanisms underlying type 2 diabetes resolution after Roux-en-Y gastric bypass (RYGB) are unclear. We suspected that glucose excretion may occur in the small bowel based on observations in humans. The aim of this study was to evaluate the mechanisms underlying serum glucose excretion in the small intestine and its contribution to glucose homeostasis after bariatric surgery., Design: 2-Deoxy-2-[ 18 F]-fluoro-D-glucose (FDG) was measured in RYGB-operated or sham-operated obese diabetic rats. Altered glucose metabolism was targeted and RNA sequencing was performed in areas of high or low FDG uptake in the ileum or common limb. Intestinal glucose metabolism and excretion were confirmed using 14 C-glucose and FDG. Increased glucose metabolism was evaluated in IEC-18 cells and mouse intestinal organoids. Obese or ob/ob mice were treated with amphiregulin (AREG) to correlate intestinal glycolysis changes with changes in serum glucose homeostasis., Results: The AREG/EGFR/mTOR/AKT/GLUT1 signal transduction pathway was activated in areas of increased glycolysis and intestinal glucose excretion in RYGB-operated rats. Intraluminal GLUT1 inhibitor administration offset improved glucose homeostasis in RYGB-operated rats. AREG-induced signal transduction pathway was confirmed using IEC-18 cells and mouse organoids, resulting in a greater capacity for glucose uptake via GLUT1 overexpression and sequestration in apical and basolateral membranes. Systemic and local AREG administration increased GLUT1 expression and small intestinal membrane translocation and prevented hyperglycaemic exacerbation., Conclusion: Bariatric surgery or AREG administration induces apical and basolateral membrane GLUT1 expression in the small intestinal enterocytes, resulting in increased serum glucose excretion in the gut lumen. Our findings suggest a novel, potentially targetable glucose homeostatic mechanism in the small intestine., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Development of drug-delivery systems that allow simultaneous in vivo imaging has gained much interest. We report a novel strategy to encapsulate metal nanoparticles (NPs) within alginate gel for in vivo imaging. The cell lysate of recombinant Escherichia coli strain, expressing Arabidopsis thaliana phytochelatin synthase and Pseudomonas putida metallothionein genes, was encapsulated within the alginate gel. Incubation of alginate gel with metal ion precursors followed by UV irradiation resulted in the synthesis of high concentrations of metal NPs, such as Au, Ag, CdSe, and EuSe NPs, within the gel. The alginate gel with metal NPs was used as a drug-delivery system by further co-encapsulating doxorubicin and rifampicin, the release of which was made to be pH-dependent. This system can be conveniently and safely used for in vitro and in vivo bioimaging, enabled by the metal NPs formed within the gel matrix without using toxic reducing reagents or surfactants.

Background and Aims: Homologous recombination deficiency (HRD) in pancreatic ductal adenocarcinoma (PDAC), remains poorly defined beyond germline (g) alterations in BRCA1, BRCA2, and PALB2., Methods: We interrogated whole genome sequencing (WGS) data on 391 patients, including 49 carriers of pathogenic variants (PVs) in gBRCA and PALB2. HRD classifiers were applied to the dataset and included (1) the genomic instability score (GIS) used by Myriad's MyChoice HRD assay; (2) substitution base signature 3 (SBS3); (3) HRDetect; and (4) structural variant (SV) burden. Clinical outcomes and responses to chemotherapy were correlated with HRD status., Results: Biallelic tumor inactivation of gBRCA or PALB2 was evident in 43 of 49 germline carriers identifying HRD-PDAC. HRDetect (score ≥0.7) predicted gBRCA1/PALB2 deficiency with highest sensitivity (98%) and specificity (100%). HRD genomic tumor classifiers suggested that 7% to 10% of PDACs that do not harbor gBRCA/PALB2 have features of HRD. Of the somatic HRDetect hi cases, 69% were attributed to alterations in BRCA1/2, PALB2, RAD51C/D, and XRCC2, and a tandem duplicator phenotype. TP53 loss was more common in BRCA1- compared with BRCA2-associated HRD-PDAC. HRD status was not prognostic in resected PDAC; however in advanced disease the GIS (P = .02), SBS3 (P = .03), and HRDetect score (P = .005) were predictive of platinum response and superior survival. PVs in gATM (n = 6) or gCHEK2 (n = 2) did not result in HRD-PDAC by any of the classifiers. In 4 patients, BRCA2 reversion mutations associated with platinum resistance., Conclusions: Germline and parallel somatic profiling of PDAC outperforms germline testing alone in identifying HRD-PDAC. An additional 7% to 10% of patients without gBRCA/PALB2 mutations may benefit from DNA damage response agents., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Since the first report of underwater adhesive proteins of marine mussels in 1981, numerous studies have reported mussel-inspired synthetic adhesive polymers. However, none of them have developed up to human-level translational studies. Here, we report a sticky polysaccharide that effectively promotes hemostasis from animal bleeding models to first-in-human hepatectomy. We found that the hemostatic material instantly generates a barrier layer that seals hemorrhaging sites. The barrier is created within a few seconds by in situ interactions with abundant plasma proteins. Therefore, as long as patient blood contains proper levels of plasma proteins, hemostasis should always occur even in coagulopathic conditions. To date, insufficient tools have been developed to arrest coagulopathic bleedings originated from genetic disorders, chronic diseases, or surgical settings such as organ transplantations. Mussel-inspired adhesion chemistry described here provides a useful alternative to the use of fibrin glues up to a human-level biomedical application., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)