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Aquaculture is notably vulnerable to diseases, with Edwardsiella tarda causing significant mortality across various commercially important fish species in both freshwater and marine environments. In the aquaculture industry, sustainable disease control hinges on the effective development of vaccines. Oral vaccines present an appealing approach to immunization in fish due to their ease of antigen administration, reduced stress compared to non-oral delivery methods, and their potential applicability to both small and large finfish species. In mammals, the exposure of mucosal surfaces to antigens results in the secretion of antigen-specific IgA at these locations. Mammals have a common mucosal immune system, in which stimulation of one epithelium can also give rise to specific IgA or IgM responses in other mucosal organs. Mucosal immunoglobulins are particularly important in developing vaccines that provide mucosal immunity. However, it remains unclear whether fish share a common mucosal system. Moreover, neither Peyer's patches nor intestinal lymph nodes were identified. Nevertheless, oral vaccination remains an attractive method for inducing immunity. We investigated whether the activation of the mucosal immune response was induced by direct injection of the antigen. After oral antigen administration, antigen-specific antibody titers increased in the experimental group (E. tarda FKC vaccine). In the challenge experiment, the cumulative survival rate was 72% (E. tarda). This suggests that oral administration of antigens can activate intestinal mucosal immunity in flounders. Additionally, these results help understand the intestinal mucosal immune system of teleost fish. In the future, research on the signaling mechanisms of these genes is expected to provide helpful information for developing vaccine adjuvants., (Copyright © 2024. Published by Elsevier Ltd.)

Infectious hematopoietic necrosis virus (IHNV) severely and lethally infects salmonid fish, including Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss) worldwide. Rapid and accurate viral detection is crucial for preventing pathogen spread and minimizing damage. Although several IHNV detection assays have been developed, their analytical and diagnostic performances have not been evaluated and field usability assessments have not been completely validated. Here, we developed a reverse-transcription cross-priming amplification-based lateral flow assay (RT-CPA-LFA) and validated its diagnostic performance. To detect the IHNV, primers were designed based on the consensus sequence of the nucleocapsid (N) gene. Notably, when combined with a lateral flow dipstick, it could visualize the IHNV amplification products within 5 min and the detection limit of the developed RT-CPA-LFA was 3.28×10 5 copies/μL. The diagnostic sensitivity and specificity in fish samples (n=140) were 98.88 % and 96.08 %, respectively. Moreover, the IHNV detection rate by RT-CPA-LFA in dead rainbow trout artificially injected with the virus was 100 %, consistent with to the results obtained from second conventional and real-time PCR, indicating its applicability for rapid IHNV detection and presumptive IHN diagnosis during the endemic period., Competing Interests: Declaration of Competing Interest The author declares no conflicts of interest, (Copyright © 2024 Elsevier B.V. All rights reserved.)

The sex-specific differences in the growth and population characteristics of the high-commercial-value sand crab Ovalipes punctatus were investigated in Korea. The estimated allometric growth between the sexes showed significant differences in all morphometric measurements. In the classification of growth types, carapace width-chela length exhibited positive and negative allometric growth in males and females, respectively. Carapace width-abdominal width showed positive relative growth in both sexes, and orbital spine width exhibited negative relative growth in both sexes. Consequently, sexual dimorphism was evident in all measured traits. Growth parameters estimated using the ELEFAN function of the FiSAT II program indicated higher values in males compared to females. Asymptotic length (CW ∞ ) for males was estimated at 139.2 mm, whereas for females it was 116.6 mm. Additionally, the growth coefficient (K) was higher in males (0.65) than in females (0.54), suggesting faster growth in males. The winter point (WP) was 1 for males and 0.7 for females, indicating slower growth in males during the colder December and slower growth in females during the spawning period in August. The modified von Bertalanffy growth curves indicated asymptotic growth in all sexes, and the growth performance index (φ') showed higher values in males (4.10) compared to females (3.87), reflecting differences in growth curves. The steady increase in recruitment rates from July to September was associated with the appearance of larvae and their subsequent growth into juveniles, leading to their recruitment into the population during this period. Therefore, O. punctatus exhibited sex-specific differences in growth parameters, suggesting distinct growth strategies between the sexes., (© 2024. The Author(s).)

Objective: Previous studies indicate that eosinophils are recruited into the allograft following orthotopic liver transplantation and protect from ischaemia reperfusion (IR) injury. In the current studies, we aim to explore whether their protective function could outlast during liver repair., Design: Eosinophil-deficient mice and adoptive transfer of bone marrow-derived eosinophils (bmEos) were employed to investigate the effects of eosinophils on tissue repair and regeneration after hepatic IR injury. Aside from exogenous cytokine or neutralising antibody treatments, mechanistic studies made use of a panel of mouse models of eosinophil-specific IL-4/IL-13-deletion, cell-specific IL-4rα-deletion in liver macrophages and hepatocytes and macrophage-specific deletion of heparin-binding epidermal growth factor-like growth factor (hb-egf)., Result: We observed that eosinophils persisted over a week following hepatic IR injury. Their peak accumulation coincided with that of hepatocyte proliferation. Functional studies showed that eosinophil deficiency was associated with a dramatic delay in liver repair, which was normalised by the adoptive transfer of bmEos. Mechanistic studies demonstrated that eosinophil-derived IL-4, but not IL-13, was critically involved in the reparative function of these cells. The data further revealed a selective role of macrophage-dependent IL-4 signalling in liver regeneration. Eosinophil-derived IL-4 stimulated macrophages to produce HB-EGF. Moreover, macrophage-specific hb-egf deletion impaired hepatocyte regeneration after IR injury., Conclusion: Together, these studies uncovered an indispensable role of eosinophils in liver repair after acute injury and identified a novel crosstalk between eosinophils and macrophages through the IL-4/HB-EGF axis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: HSCs contribute to HCC progression by regulating multiple factors. However, the entire immunoregulatory functions of HSCs are still obscure. Here, we aim to investigate whether HSCs impose CX 3 CR1 + macrophages to protumorigenic properties in the peritumoral area., Approach and Results: In single-cell RNA-sequencing analysis of patients with HCC, a subpopulation of macrophages specifically expressed Arg1 and Cx3cr1 in the peritumoral area and were highly enriched with retinol metabolism-related genes. Flow cytometry analysis showed significantly increased frequencies of CD14 + CD11b + HLA-DR - macrophages with CX 3 CR1 in the HCC adjacent region where α-smooth muscle actin-expressing activated hepatic stellate cells (aHSCs) showed colocalized expression of CX 3 CL1. Accordingly, in tumor-bearing mice, Cx3cl1 mRNA expression was notably increased in aHSCs within the adjacent HCC, where infiltration of CX 3 CR1 + Ly6C + macrophages was mostly observed with decreased CD8 + T cells. In adoptive transfer and in vitro coculture of myeloid cells, we demonstrated that CX 3 CR1 + Ly6C + macrophages migrated and highly expressed arginase-1 by interacting with retinoid-enriched aHSCs in the adjacent HCC. Direct treatment of retinoids or coculturing with retinol-storing mouse aHSCs or human LX-2 cells significantly increased arginase-1 expression in CX 3 CR1 + Ly6C + macrophages and human blood CD14 + cells, leading to the suppression of CD8 + T-cell proliferation. Moreover, genetic deficiency of CX 3 CR1 in myeloid cells or pharmacological inhibition of retinol metabolism remarkably attenuated HCC development., Conclusions: We showed that CX 3 CR1 + Ly6C + macrophages migrate and interact with aHSCs in the peritumoral region where retinoids induce arginase-1 expression in CX 3 CR1 + Ly6C + macrophages, subsequently depriving CD8 + T cells of arginine and promoting HCC., (Copyright © The Author(s). Published by Wolters Kluwer Health, Inc.)

An 8-month-old, 3.4 kg, castrated male Toy Poodle was referred for progressive tetraparesis and respiratory disorder without a history of trauma. Repeated computed tomography (CT) and magnetic resonance imaging (MRI) with different positions of the neck revealed concurrent atlanto-occipital dislocation (AOD) and atlantoaxial instability (AAI) with spinal cord compression. This case was unique due to its congenital nature and the absence of trauma. The surgical treatment involved precise removal of the C1 vertebra's ventral articular facet, which was compressing on the spinal cord, attributed to its fixed and malaligned position within the atlantooccipital joint. Following facetectomy, the stabilization of the occipital bone to the C2 vertebra was achieved by screws, wire, and polymethyl methacrylate. Two days after surgery, the dog recovered ambulation and showed gradual improvement in gait, despite mild residual ataxia. Postoperative CT and radiographs showed successful decompression of the spinal cord. The screw loosening was confirmed at 114 days, which was managed successfully by extracting the affected screws. Through the 21-month monitoring period, the dog showed a normal gait with a wide-based stance of the pelvic limbs when standing and experienced no pain. This case represents the first report of concurrent congenital AOD and AAI treated with a ventral surgical approach, contributing new insights to the understanding and management of such complex cranio-cervical junction disorders in veterinary neurosurgery.

A deep convolutional neural network (DCNN) architecture ResNet has been tested to verify its ability to handle selected area electron diffraction pattern (SADP) datasets carrying information on lattice defects including strains, thermal lattice vibrations, point defects, dislocations, and twin boundaries. The disordered states of the crystal lattices in the presence of these defects were predicted by ab initio molecular dynamics simulations, first principles geometry optimizations, and lattice manipulation operations in an effort to establish a possible dataset augmentation strategy for the improvement of classification performance of the ResNet. Using the disordered lattice information originating from the defects, test dataset SADPs were generated by simulating electron diffraction in transmission electron microscopy. The ResNet, pre-trained using SADPs from defect-free materials, showed decreasing but acceptable classification accuracies with increasing degrees of lattice disorder regarding the lattice vibrations and point defects. When tested using the diffraction patterns for strained lattices, the ResNet responded to the changing lattice symmetry when strain levels are relatively high suggesting that it has capability to discern different symmetries induced by large strains. However, the ResNet failed to recognize lattice structure when dislocations and twin boundaries were considered. It is suggested that DCNN architectures be trained over various scenarios including changes in the image feature characteristics in the diffraction patterns related to defects in future developments for improved general classification performances., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A 2-year-old, intact female Pomeranian presented with bilateral forelimb lameness, characterized by the olecranon making contact with the ground. The patient experienced two separate incidents of falling, occurring four and three weeks before admission, respectively. Following each episode, non-weight-bearing lameness was initially observed in the left forelimb, followed by the development of crouch gait. Based on the physical examination, radiographic, and ultrasonographic findings, bilateral triceps brachii tendon disruption was diagnosed. Intraoperatively, excessive granulation tissue at the distal end of the tendon was excised. The footprint region of each triceps brachii tendon was decorticated with a high-speed burr until bleeding was observed. The triceps brachii tendon was reattached to completely cover its footprint on the olecranon using the Krackow suture technique. This method involves anchoring the suture through bone tunnels in the ulna. Trans-articular external skeletal fixation was applied to both forelimbs to immobile and stabilize the elbow joints for nine weeks. Subsequently, the dog gradually increased its walking activities while on a leash over a six-week period. At the three-year follow-up, the patient exhibited improved forelimb function and maintained a normal gait without signs of lameness. Suture-mediated anatomic footprint repair proved useful in this single case and may be an effective surgical alternative for the management of chronic triceps brachii tendon disruption in dogs.

Periodontal disease represents a condition that exhibits substantial global morbidity, and is characterized by the infection and inflammation of the periodontal tissue effectuated by bacterial pathogens. The present study aimed at evaluating the therapeutic efficacy of BenTooth, an edible natural product mixture comprising burdock root extract, persimmon leaf extract and quercetin, against periodontitis both in vitro and in vivo . BenTooth was examined for antimicrobial properties and its impact on cellular responses related to inflammation and bone resorption. Its effects were also assessed in a rat model of ligature-induced periodontitis. BenTooth demonstrated potent antimicrobial activity against P. gingivalis and S. mutans . In RAW264.7 cells, it notably diminished the expression of inducible nitric oxide synthase and cyclooxygenase-2, as well as reduced interleukin-6 and tumor necrosis factor-α levels triggered by P. gingivalis -derived lipopolysaccharide. Furthermore, BenTooth inhibited osteoclastogenesis mediated by the receptor activator of nuclear factor κB ligand. In the rat model, BenTooth consumption mitigated the ligature-induced expansion in distance between the cementoenamel junction and the alveolar bone crest and bolstered the bone volume fraction. These results present BenTooth as a potential therapeutic candidate for the prevention and remediation of periodontal diseases., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:The authors declare the following competing interests: M.H.D., H.L., S.Y.S., S.Y.C., S.O., and J-M.J. are employees of Ben's Lab Co., Ltd. BenTooth is related to products of Ben's Lab Co., Ltd. that are in development. However, this does not alter our adherence to Heliyon policies on sharing data and materials. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Metastructures, artificial arrangements of micro/macrostructures, possess unique properties and are of significant interest in aerospace, stealth technology, and various other applications. Recent studies have focused on quasi-zero stiffness metastructures, providing an outstanding vibration isolation capability. However, existing methods are constrained to low preloads and lack the consideration of structural analysis, despite their intended use in practical structures. This study introduces metastructures with quasi-zero stiffness characteristics under high preloads by inducing local buckling. An optimization framework combining deep reinforcement learning and finite-element analysis is employed to derive an optimal model that considers both structural safety and quasi-zero stiffness characteristics. To validate the optimization results, quasi-zero stiffness metastructures are fabricated via 3D printing, and compression and vibration experiments are conducted. The fabricated metastructures exhibit quasi-zero stiffness characteristics under a high target preload along with outstanding vibration reduction performance, even in the low-frequency range.

Background: Under conditions of hypoxia, cancer cells with hypoxia inducible factor-1α (HIF-1α) from heterogeneous tumor cells show greater aggression and progression in an effort to compensate for harsh environmental conditions. Extensive study on the stability of HIF-1α under conditions of acute hypoxia in cancer progression has been conducted, however, understanding of its involvement during the chronic phase is limited., Methods: In this study, we investigated the effect of SIRT1 on HIF1 stability in a typical chronic hypoxic conditon that maintains cells for 24 h under hypoxia using Western blotting, co-IP, measurement of intracellular NAD + and NADH levels, semi-quantitative RT-PCR analysis, invasion assay, gene knockdown., Results: Here we demonstrated that the high concentration of pyruvate in the medium, which can be easily overlooked, has an effect on the stability of HIF-1α. We also demonstrated that NADH functions as a signal for conveyance of HIF-1α degradation via the SIRT1 and VHL signaling pathway under conditions of chronic hypoxia, which in turn leads to attenuation of hypoxically strengthened invasion and angiogenic activities. A steep increase in the level of NADH occurs during chronic hypoxia, leading to upregulation of acetylation and degradation of HIF-1α via inactivation of SIRT1. Of particular interest, p300-mediated acetylation at lysine 709 of HIF-1α is recogonized by VHL, which leads to degradation of HIF-1α via ubiquitin/proteasome machinary under conditions of chronic hypoxia. In addition, we demonstrated that NADH-elevation-induced acetylation and subsequent degradation of HIF-1α was independent of proline hydroxylation., Conclusions: Our findings suggest a critical role of SIRT1 as a metabolic sensor in coordination of hypoxic status via regulation of HIF-1α stability. These results also demonstrate the involvement of VHL in degradation of HIF-1α through recognition of PHD-mediated hydroxylation in normoxia and p300-mediated HIF-1α acetylation in hypoxia., (© 2023. Society of Chinese Bioscientists in America (SCBA).)

In a short time, several types of injectable and oral therapeutics have been developed and used to effectively manage patients with coronavirus disease 2019 (COVID-19). BEN815 is an improved mixture of three extracts (Psidium guajava, Camellia sinensis, and Rosa hybrida) recognized by the Ministry of Food and Drug Safety of Korea as a health food ingredient that alleviates allergic rhinitis. The current animal efficacy study was performed to assess its probability of improving COVID-19 symptoms. BEN815 treatment significantly increased the survival of K18-hACE2 transgenic mice and reduced viral titers in the lungs at 5 days post infection (DPI). Furthermore, the lungs of the treated mice showed mild tissue damage at 5 DPI and nearly complete recovery from COVID-19 at 14 DPI. BEN815 appears to be an effective and minimally toxic anti-SARS-CoV-2 agent in mice and has potential for clinical applications., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Do et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Recent research suggests that persimmon leaf extract (PLE) has an effect on inflammatory skin diseases. Previously, PLE is revealed to inhibit not only nitric oxide production but also inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression levels in mouse macrophages in vitro. Moreover, it significantly reduced IL-6 production and 5α-reductase expression in human follicle dermal papilla cells (HFDPCs). This study aimed to determine whether the PLE-containing BLH308 complex improves hair growth in clinical trials., Materials and Methods: A total of 88 participants were recruited, and were instructed to orally take BLH308 or the placebo twice a day for 24 weeks. The mean age of the test group was 38.52 ± 7.98 years and that of placebo group was 38.98 ± 8.80 years. The study was conducted for 24 weeks, and hair density, thickness, and gloss were evaluated. All participants completed a satisfaction survey questionnaire., Results: The test group showed significantly increased hair density and hair diameter at week 24 compared with the placebo group (p = 0.0015 and p = 0.0001, respectively). Although not statistically significant, the degree of gloss also showed higher improvement in the test group compared to the placebo group., Conclusions: Our data demonstrated that oral consumption of the BLH308 complex containing PLE significantly increased hair density and thickness compared to the placebo group, showing its possible role in promoting hair growth., (© 2023 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)

A fast and straightforward fabrication process for producing a robust, flexible, and transparent conductive film was demonstrated using nanowelding of Ag nanowires through pressure-assisted microwave irradiation. This innovative process effectively reduces the sheet resistance of the Ag nanowire transparent conductive film without causing any thermal distortion to the PET substrate. The microwave irradiation induces nanowelding between Ag nanowires, leading to a decrease in sheet resistance by forming nanowelding junctions. This selective heating of Ag nanowires further enhances the reduction in sheet resistance. Additionally, the application of pressure-assisted microwave irradiation allows the Ag nanowires to be embedded into the PET substrate, resulting in the formation of a robust film capable of withstanding cycling bending stress. The pressure-assisted microwave irradiation process proves to be a strong fabrication method for creating Ag nanowire transparent conductive films, especially when dealing with thermally weak substrate materials., (© 2023. Springer Nature Limited.)

Shape memory polymer composite (SMPC) actuators have received significant attention for applications in space deployable structures because of their light weight and simple actuating process without any additional components. However, conventional SMPC actuators exhibit limited deformation owing to damages caused by the slight elongation of fibers and microbuckling. In this study, we designed a sandwich-structured SMPC bending actuator to increase deformability and the recovery moment with two novel features: multiple neutral axis (MNA) skins and a deployable core. The MNA skins were fabricated as layered structures of a soft layer (the polydimethylsiloxane/ethoxylated polyethylenimine layer) and hard layers (the SMPC layer) based on the MNA effect derived from the large modulus difference between the soft and hard layers. Under the bending deformation, the large shear strain in the soft layer significantly decreases the axial strain in SMPC layers and increases deformability. Applying the deployable core on the sandwich-structured SMPC bending actuator increases the recovery moment owing to the deploying force of the core. To the best of our knowledge, the sandwich-structured SMPC bending actuator composed of two MNA skins and a deployable core yielded the world's largest width-normalized recovery moment of 51.2 N·m/m with the smallest bending radius of 15 mm.

The globally accepted evaluation method for facial palsy is the House-Brackmann facial grading system; however, it does not reflect minute changes. Several methods have been attempted, but there is no universally accepted evaluation method that is non-time-consuming and quantitative. Recently, Emotrics, a two-dimensional analysis that incorporates machine-learning techniques, has been used in various clinical fields. However, its reliability and validity have not yet been determined. Therefore, this study aimed to examine and establish the reliability and validity of Emotrics. All patients had previously received speech therapy for facial palsy at our hospital between January and November 2022. In speech therapy at our hospital, Emotrics was routinely used to measure the state of the patient's facial palsy. A frame was created to standardize and overcome the limitation of the two-dimensional analysis. Interrater, intrarater, and intrasubject reliability were evaluated with intraclass correlation coefficients (ICC) by measuring the indicators that reflect eye and mouth functions. Validity was evaluated using Spearman's correlation for each Emotrics parameter and the House-Brackmann facial grading system. A total of 23 patients were included in this study. For all parameters, there was significant interrater and intrarater reliability (ICC, 0.61 to 0.99). Intrasubject reliability showed significant reliability in most parameters (ICC, 0.68 to 0.88). Validity showed a significant correlation in two parameters ( p -value < 0.001). This single-center study suggests that Emotrics could be a quantitative and efficient facial-palsy evaluation method with good reliability. Therefore, Emotrics is expected to play a key role in assessing facial palsy and in monitoring treatment effects more accurately and precisely.

Background: Among the four genicular nerves innervating the anterior aspect of the knee, the inferior lateral genicular nerve has been omitted as a target of blocking. Some authors have suggested that the inferior lateral genicular nerve of the knee might pass beneath the lateral collateral ligament of knee. The authors aimed to study the location of the inferior lateral genicular nerve and the spread of injectate during the inferior lateral genicular nerve block., Methods: In ten knees from fresh frozen cadavers, the authors performed on each an ultrasound-guided block of the inferior lateral genicular nerve of the knee just below the lateral collateral ligament. The needle was inserted below the lateral collateral ligament, and 2 mL of blue dye was injected. A week later, the cadavers were dissected, and the existence of the inferior lateral genicular nerve and the spread of dye around it was investigated., Results: The proportion of inferior lateral genicular nerves branching from the common peroneal nerve was found in 8 of 10 (80.0%) cadavers. Of these eight cadavers with inferior lateral genicular nerve, five specimens (62.5%) were stained with blue dye. The common peroneal nerve was not infiltrated with dye in any specimens., Conclusions: When 2 mL of dye was inserted inferiorly to the lateral collateral ligament, the inferior lateral genicular nerve could be blocked in 62.5% of specimens. Because the common peroneal nerve was not involved in any specimen, motor weakness would be avoided with this method.

Background and Aims: Insufficient liver regeneration causes post-hepatectomy liver failure and small-for-size syndrome. Identifying therapeutic targets to enhance hepatic regenerative capacity remains urgent. Recently, increased IL-33 was observed in patients undergoing liver resection and in mice after partial hepatectomy (PHx). The present study aims to investigate the role of IL-33 in liver regeneration after PHx and to elucidate its underlying mechanisms., Approach and Results: We performed PHx in IL-33 -/- , suppression of tumorigenicity 2 (ST2) -/- , and wild-type control mice, and found deficiency of IL-33 or its receptor ST2 delayed liver regeneration. The insufficient liver regeneration could be normalized in IL-33 -/- but not ST2 -/- mice by recombinant murine IL-33 administration. Furthermore, we observed an increased level of serotonin in portal blood from wild-type mice, but not IL-33 -/- or ST2 -/- mice, after PHx. ST2 deficiency specifically in enterochromaffin cells recapitulated the phenotype of delayed liver regeneration observed in ST2 -/- mice. Moreover, the impeded liver regeneration in IL-33 -/- and ST2 -/- mice was restored to normal levels by the treatment with (±)-2,5-dimethoxy-4-iodoamphetamine, which is an agonist of the 5-hydroxytrytamine receptor (HTR)2A. Notably, in vitro experiments demonstrated that serotonin/HTR2A-induced hepatocyte proliferation is dependent on p70S6K activation., Conclusions: Our study identified that IL-33 is pro-regenerative in a noninjurious model of liver resection. The underlying mechanism involved IL-33/ST2-induced increase of serotonin release from enterochromaffin cells to portal blood and subsequent HTR2A/p70S6K activation in hepatocytes by serotonin. The findings implicate the potential of targeting the IL-33/ST2/serotonin pathway to reduce the risk of post-hepatectomy liver failure and small-for-size syndrome., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Efficient water disinfection is vitally needed in rural and disaster-stricken areas lacking power supplies. However, conventional water disinfection methods strongly rely on external chemical input and reliable electricity. Herein, we present a self-powered water disinfection system using synergistic hydrogen peroxide (H 2 O 2 ) assisted electroporation mechanisms driven by triboelectric nanogenerators (TENGs) that harvest electricity from the flow of water. The flow-driven TENG, assisted by power management systems, generates a controlled output with aimed voltages to drive a conductive metal-organic framework nanowire array for effective H 2 O 2 generation and electroporation. The injured bacteria caused by electroporation can be further damaged by facile diffused H 2 O 2 molecules at high throughput. A self-powered disinfection prototype enables complete disinfection (>99.9999% removal) over a wide range of flows up to 3.0 × 10 4 L/(m 2 h) with low water flow thresholds (200 mL/min; ∼20 rpm). This rapid, self-powered water disinfection method is promising for pathogen control.

Background and Aims: A better understanding of the underlying mechanism of acetaminophen (APAP)-induced liver injury (AILI) remains an important endeavor to develop therapeutic approaches. Eosinophils have been detected in liver biopsies of patients with APAP overdose. We recently demonstrated a profound protective role of eosinophils against AILI; however, the molecular mechanism had not been elucidated., Approach and Results: In agreement with our previous data from experiments using genetic deletion of eosinophils, we found that depletion of eosinophils in wild-type (WT) mice by an anti-IL-15 antibody resulted in exacerbated AILI. Moreover, adoptive transfer of eosinophils significantly reduced liver injury and mortality rate in WT mice. Mechanistic studies using eosinophil-specific IL-4/IL-13 knockout mice demonstrated that these cytokines, through inhibiting interferon-γ, mediated the hepatoprotective function of eosinophils. Reverse phase protein array analyses and in vitro experiments using various inhibitors demonstrated that IL-33 stimulation of eosinophils activated p38 mitogen-activated protein kinase (MAPK), and in turn, cyclooxygenases (COX), which triggered NF-κB-mediated IL-4/IL-13 production. In vivo adoptive transfer experiments showed that in contrast to naive eosinophils, those pretreated with COX inhibitors failed to attenuate AILI., Conclusions: The current study revealed that eosinophil-derived IL-4/IL-13 accounted for the hepatoprotective effect of eosinophils during AILI. The data demonstrated that the p38 MAPK/COX/NF-κB signaling cascade played a critical role in inducing IL-4/IL-13 production by eosinophils in response to IL-33., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Graphene inks have recently attracted attention for the development of printed wearable and flexible electronics and sensors not only because of their high conductivity and low cost but also because they are suitable for high-speed printing. Although reliable and scalable printing technologies are well established, further improvement in graphene inks in terms of electrical conductivity, stretchability/flexibility, and mass production is necessary for sensors for real-time monitoring. Herein, highly stretchable and conductive graphene inks were prepared by an efficient and scalable fluid dynamics-assisted exfoliation of graphite and a mixing process with elastomeric Ecoflex. After printing inks onto textile substrates, the serpentine-patterned conductors exhibited high conductivity and stable resistance even under a mechanically stretched state (a strain of 150%). Electrochemical sensors that detect sodium ions were fabricated on this conducting platform. These sensors indicated high potentiometric sensing ability under different mechanical deformations. To demonstrate the on-body performance of the developed sensors, real-time monitoring of sodium-ion concentration in the sweat of a human subject was carried out during an indoor stationary cycling exercise.

Objective: 68 Ga-NGUL is a novel prostate-specific membrane antigen (PSMA)-targeting tracer based on Glu-Urea-Lys derivatives conjugated to a 1,4,7-triazacyclononane- N , N ', N ″-triacetic acid (NOTA) chelator via a thiourea-type short linker. This phase I clinical trial of 68 Ga-NGUL was conducted to evaluate the safety and radiation dosimetry of 68 Ga-NGUL in healthy volunteers and the lesion detection rate of 68 Ga-NGUL in patients with prostate cancer., Materials and Methods: We designed a prospective, open-label, single-arm clinical trial with two cohorts comprising six healthy adult men and six patients with metastatic prostate cancer. Safety and blood test-based toxicities were monitored throughout the study. PET/CT scans were acquired at multiple time points after administering 68 Ga-NGUL (2 MBq/kg; 96-165 MBq). In healthy adults, absorbed organ doses and effective doses were calculated using the OLINDA/EXM software. In patients with prostate cancer, the rates of detecting suspicious lesions by 68 Ga-NGUL PET/CT and conventional imaging (CT and bone scintigraphy) during the screening period, within one month after recruitment, were compared., Results: All 12 participants (six healthy adults aged 31-32 years and six prostate cancer patients aged 57-81 years) completed the clinical trial. No drug-related adverse events were observed. In the healthy adult group, 68 Ga-NGUL was rapidly distributed, with the highest uptake in the kidneys. The median effective dose coefficient was calculated as 0.025 mSv/MBq, and cumulative activity in the bladder had the highest contribution. In patients with metastatic prostate cancer, 229 suspicious lesions were detected using either 68 Ga-NGUL PET/CT or conventional imaging. Among them, 68 Ga-NGUL PET/CT detected 199 (86.9%) lesions and CT or bone scintigraphy detected 114 (49.8%) lesions., Conclusion: 68 Ga-NGUL can be safely applied clinically and has shown a higher detection rate for the localization of metastatic lesions in prostate cancer than conventional imaging. Therefore, 68 Ga-NGUL is a valuable option for prostate cancer imaging., Competing Interests: Gi Jeong Cheon who is on the editorial board of the Korean Journal of Radiology was not involved in the editorial evaluation or decision to publish this article. All remaining authors have declared no conflicts of interest., (Copyright © 2022 The Korean Society of Radiology.)

Background & Aims: Beyond the classical description of eosinophil functions in parasite infections and allergic diseases, emerging evidence supports a critical role of eosinophils in resolving inflammation and promoting tissue remodeling. However, the role of eosinophils in liver injury and the underlying mechanism of their recruitment into the liver remain unclear., Methods: Hepatic eosinophils were detected and quantified using flow cytometry and immunohistochemical staining. Eosinophil-deficient (ΔdblGata1) mice were used to investigate the role of eosinophils in 3 models of acute liver injury. In vivo experiments using Il33 -/- mice and macrophage-depleted mice, as well as in vitro cultures of eosinophils and macrophages, were performed to interrogate the mechanism of eotaxin-2 (CCL24) production., Results: Hepatic accumulation of eosinophils was observed in patients with acetaminophen (APAP)-induced liver failure, whereas few eosinophils were detectable in healthy liver tissues. In mice treated with APAP, carbon tetrachloride or concanavalin A, eosinophils were recruited into the liver and played a profound protective role. Mice deficient of macrophages or IL-33 exhibited impaired hepatic eosinophil recruitment during acute liver injury. CCL24, but not CCL11, was increased after treatment of each hepatotoxin in an IL-33 and macrophage-dependent manner. In vitro experiments demonstrated that IL-33, by stimulating IL-4 release from eosinophils, promoted the production of CCL24 by macrophages., Conclusions: This is the first study to demonstrate that hepatic recruitment of and protection by eosinophils occur commonly in various models of acute liver injury. Our findings support further exploration of eosinophils as a therapeutic target to treat APAP-induced acute liver injury., Lay Summary: The current study unveils that eosinophils are recruited into the liver and play a protective function during acute liver injury caused by acetaminophen overdose. The data demonstrate that IL-33-activated eosinophils trigger macrophages to release high amounts of CCL24, which promotes hepatic eosinophil recruitment. Our findings suggest that eosinophils could be an effective cell-based therapy for the treatment of acetaminophen-induced acute liver injury., Competing Interests: Conflict of interest The authors declare that they have no competing interests. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

A number of researchers in Korea have tried to set-up the production of radionuclides and develop new radiopharmaceuticals for several decades. Thanks to their 60-year endeavor to advance the field of radiopharmaceutical sciences, now we have a lot of research units and facilities in Korea. Still, there are huge number of issues to be solved in radiopharmaceutical sciences; however, our efforts will be continued to develop new radiopharmaceuticals and to apply the new radiopharmaceuticals into nuclear medicine field., Competing Interests: Conflict of InterestRan Ji Yoo, Yun-Sang Lee, Kyo Chu Lee, Dong Wook Kim, Dong-Yeon Kim, Yearn Seong Choe, and Jae Min Jeong declare no conflict of interests., (© The Author(s), under exclusive licence to Korean Society of Nuclear Medicine 2022.)

Background: Smad4 and p53 mutations are the most common mutations in human colorectal cancers (CRCs). We evaluated whether and how they are synergistic in intestinal carcinogenesis using novel autochthonous mouse models., Method: To recapitulate human CRCs, we generated Villin-Cre;Smad4 F / F ;Trp53 F / F mice. We then compared the intestinal phenotype of Villin-Cre;Smad4 F / F ;Trp53 F / F mice (n = 40) with Villin-Cre;Smad4 F / F (n = 30) and Villin-Cre;Trp53 F / F mice (n = 45)., Results: Twenty-week-old Villin-Cre;Smad4 F / F ;Trp53 F / F mice displayed spontaneous highly proliferative intestinal tumors, and 85% of mice developed adenocarcinomas. p21 was downregulated in the intestinal mucosa in Villin-Cre;Smad4 F / F ;Trp53 F / F mice than in Villin-Cre;Smad4 F / F and Villin-Cre;Trp53 F / F mice. Villin-Cre;Smad4 F / F ;Trp53 F / F mice displayed multistep intestinal tumorigenesis and Wnt activation. Long-term CWP232291 (small-molecule Wnt inhibitor) treatment of Villin-Cre;Smad4 F / F ;Trp53 F / F mice suppressed intestinal tumorigenesis and progression. CWP232291 treatment downregulated cancer stem cell (CSC) tumor markers including CD133, Lgr-5, and Sca-1. CWP232291 treatment reduced the CSC frequency. Small-molecule Wnt inhibitors reduced intestinal CSC populations and inhibited their growth, along with Bcl-X L downregulation. Furthermore, BH3I-1, a Bcl-X L antagonist, increasingly inhibited intestinal CSCs than bulk tumor cells., Conclusion: Smad4 loss and p53 loss are synergistic in autochthonous intestinal carcinogenesis, by downregulating p21 and activating Wnt/β-catenin pathway., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Hypoxia in cervical cancer has been associated with a poor prognosis. Over the years 68 Ga labelled nitroimidazoles have been studied and have shown improved kinetics. We present our initial experience of hypoxia Positron Emission Tomography (PET) imaging in cervical cancer with 68 Ga-Nitroimidazole derivative and the correlation with 18 F-FDG PET/CT and immunohistochemistry. Twenty women with cervical cancer underwent both 18 F-FDG and 68 Ga-Nitroimidazole PET/CT imaging. Dual-point imaging was performed for 68 Ga-Nitroimidazole PET. Immunohistochemical analysis was performed with hypoxia inducible factor-1α (HIF-1α). We documented SUVmax, SUVmean of the primary lesions as well as tumor to muscle ratio (TMR), tumor to blood (TBR), metabolic tumor volume (MTV) and hypoxic tumor volume (HTV). There was no significant difference in the uptake of 68 Ga-Nitroimidazole between early and delayed imaging. Twelve patients had uptake on 68 Ga-Nitroimidazole PET. Ten patients demonstrated varying intensities of HIF-1α expression and six of these also had uptake on 68 Ga-Nitroimidazole PET. We found a strong negative correlation between HTV and immunohistochemical staining (r = -0.660; p = 0.019). There was no correlation between uptake on PET imaging and immunohistochemical analysis with HIF-1α. Two-thirds of the patients demonstrated hypoxia on 68 Ga-Nitroimidazole PET imaging.

Investigations have been made to explore the applicability of an off-the-shelf deep convolutional neural network (DCNN) architecture, residual neural network (ResNet), to the classification of the crystal structure of materials using electron diffraction patterns without prior knowledge of the material systems under consideration. The dataset required for training and validating the ResNet architectures was obtained by the computer simulation of the selected area electron diffraction (SAD) in transmission electron microscopy. Acceleration voltages, zone axes, and camera lengths were used as variables and crystal information format (CIF) files obtained from open crystal data repositories were used as inputs. The cubic crystal system was chosen as a model system and five space groups of 213, 221, 225, 227, and 229 in the cubic system were selected for the test and validation, based on the distinguishability of the SAD patterns. The simulated diffraction patterns were regrouped and labeled from the viewpoint of computer vision, i.e. , the way how the neural network recognizes the two-dimensional representation of three-dimensional lattice structure of crystals, for improved training and classification efficiency. Comparison of the various ResNet architectures with varying number of layers demonstrated that the ResNet101 architecture could classify the space groups with the validation accuracy of 92.607%., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: The corona virus disease 2019 (COVID-19) pandemic has highlighted the fact that there are few effective antiviral agents for treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Although the very recent development of vaccines is an extremely important breakthrough, it remains unclear how long-lived such vaccines will be. The development of new agents therefore remains an important goal., Purpose: Given the multifaceted pathology of COVID-19, a combinatorial formulation may provide an effective treatment. BEN815, a natural nutraceutical composed of extracts from guava leaves ( Psidium guajava ), green tea leaves ( Camellia sinensis ), and rose petals ( Rosa hybrida ), had previously shown to have a therapeutic effect on allergic rhinitis. We investigated whether BEN815 possesses anti-inflammatory, antiviral and antioxidant activities, since the combination of these effects could be useful for the treatment of COVID-19., Study Design: We examined the anti-inflammatory effects of BEN815 and its principal active components quercetin and epigallocatechin gallate (EGCG) in lipopolysaccharide (LPS)-induced RAW264.7 cells and in an LPS-challenged mouse model of endotoxemia. We also assessed the antioxidant activity, and antiviral effect of BEN815, quercetin, and EGCG in SARS-CoV-2-infected Vero cells., Methods: The principal active ingredients in BEN815 were determined and quantified using HPLC. Changes in the levels of LPS-induced pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured by ELISA. Changes in the expression levels of cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) were analyzed using western blotting. Antioxidant assay was performed using DPPH and ABTS assay. SARS-CoV-2 replication was measured by immunofluorescence staining., Results: BEN815 significantly suppressed the induction of IL-6 and TNF-α as well as COX-2 and iNOS in LPS-induced RAW264.7 cells. In addition, BEN815 protected against LPS-challenged endotoxic shock in mice. Two major constituents of BEN815, quercetin and EGCG, reduced the induction of IL-6 and TNF-α as well as COX-2 and iNOS synthase in LPS-induced RAW264.7 cells. BEN815, quercetin, and EGCG were also found to have antioxidant effects. Importantly, BEN815 and EGCG could inhibit SARS-CoV-2 replications in Vero cells., Conclusion: BEN815 is an anti-inflammatory, antiviral, and antioxidant natural agent that can be used to prevent and improve inflammation-related diseases, COVID-19., Competing Interests: We confirm that there are no conflicts of interest associated with this publication and there has no significant financial support for this work that could have influenced its outcome., (© 2021 The Authors. Published by Elsevier B.V.)

68 Ga-NOTA Glu-Urea-Lys (NGUL) is a novel prostate-specific membrane antigen (PSMA)-targeting tracer used for PET/CT imaging. This study aimed to compare performance in the detection of primary and metastatic lesions and to compare biodistribution between 68 Ga-NGUL and 68 Ga-PSMA-11 in the same patients with prostate cancer. Methods: Eleven patients with metastatic prostate cancer were prospectively recruited. The quantitative tracer uptake was determined in normal organs and in primary and metastatic lesions. Results: 68 Ga-NGUL showed significantly lower normal-organ uptake and rapid urinary clearance. The number and sites of detected PSMA-positive primary and metastatic lesions were identical, and no significant quantitative uptake difference was observed. 68 Ga-NGUL showed a relatively lower tumor-to-background ratio than 68 Ga-PSMA-11. Conclusion: In a head-to-head comparison with 68 Ga-PSMA-11, 68 Ga-NGUL showed lower uptake in normal organs and similar performance in detecting PSMA-avid primary and metastatic lesions. 68 Ga-NGUL could be a valuable option for PSMA imaging., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

Cancer of the cervix is the fourth commonest malignancy in women worldwide and it also ranks fourth as the cause of cancer related mortality in women. Hypoxia is a common characteristic of solid tumours and cervical cancer is no exception. Hypoxia is associated with increased aggressiveness, risk of invasion and metastasis. Tumour hypoxia also results in resistance to both radiation therapy and chemotherapy leading to a poorer prognosis. In-vivo measurement of tumour hypoxia is vital in oncologic practice because it can predict outcome and identify patients with a worse prognosis. Mapping of tumour hypoxia may also help select patients that may benefit from applicable treatments. While traditional methods of measuring hypoxia such as the Eppendorf probe is considered the gold standard, it is invasive and technically demanding. Non-invasive methods of measuring tumourhypoxia are ideal. Positron emission tomography/computed tomography (PET/CT) imaging with nitro-imidazole-based tracers is a highly sensitive nuclear imaging technique that is suited for non-invasive in vivo monitoring of hypoxia. Over the years various hypoxia specific PET tracers have been investigated in various malignancies including cancer of the cervix. Several fluorine-18 ( 18 F)-based tracers have been studied and although most had small patient numbers, the results are promising and generally demonstrate an associate between the presence of hypoxia and treatment outcome. The need for an onsite cyclotron and specialized radiopharmacy skills make these tracers unattractive and largely unavailable for routine clinical applications. With the increase in availability of the gallium-68 ( 68 Ga) generator this makes the 68 Ga-labelled nitroimidazole derivatives attractive because 68 Ga is available from a generator with a shelf life of almost a year. The chemistry of 68 Ga makes for easy labelling with several peptides and molecules. Pre-clinical work has demonstrated the feasibility of using these tracers for imaging hypoxia and has laid the groundwork for further human studies with these tracers.The aim of this review is to discuss hypoxia and its impact in cancer of the cervix as well as to look into the progress made in hypoxia imaging in cancer of the cervix. This will focus on the tracers studied thus far and some of the challenges of hypoxia imaging.

Fisheries activities for supplying marine productions were excessively overwhelming. Furthermore in the competitive industrialization, the impact on marine ecosystems and fisheries resources are severe due to the increase of various seabed litter such as plastic materials, styrofoam and plastic bottles and the deterioration of the marine environment. Despite these seriously situation, very few studies of some sea of Korea have been carried out on sedimentary waste fishing. Also some fisheries and there are few reports on plastics present on the seabed of around Korea. This study investigated the distribution of seabed litter collected from the seabed and characteristics of each area by using the trawl gear of the survey vessel from February to November 2018. The weight of all seabed litter collected during the investigation was 62,541.5 kg km -2 , with a range of 0.2-15,019.7 kg km -2 . The most amount of seabed litter was collected from sea block 106 in the South Sea, followed by sea blocks 76 and 82 in the East Sea. Through this study, which was conducted for the first time in all sea in around Korea, it can be used as basic data to understand the current status of seabed litter in the seabed and to establish effective policies at the led by the government., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Non-invasive imaging techniques (especially single-photon emission tomography and positron emission tomography) apply several RGD-based imaging ligands developed during a vast number of preclinical and clinical investigations. The RGD (Arg-Gly-Asp) sequence is a binding moiety for a large selection of adhesive extracellular matrix and cell surface proteins. Since the first identification of this sequence as the shortest sequence required for recognition in fibronectin during the 1980s, fundamental research regarding the molecular mechanisms of integrin action have paved the way for development of several pharmaceuticals and radiopharmaceuticals with clinical applications. Ligands recognizing RGD may be developed for use in the monitoring of these interactions (benign or pathological). Although RGD-based molecular imaging has been actively investigated for oncological purposes, their utilization towards non-oncology applications remains relatively under-exploited., Methods and Scope: This review highlights the new non-oncologic applications of RGD-based tracers (with the focus on single-photon emission tomography and positron emission tomography). The focus is on the last 10 years of scientific literature (2009-2020). It is proposed that these imaging agents will be used for off-label indications that may provide options for disease monitoring where there are no approved tracers available, for instance Crohn's disease or osteoporosis. Fundamental science investigations have made progress in elucidating the involvement of integrin in various diseases not pertaining to oncology. Furthermore, RGD-based radiopharmaceuticals have been evaluated extensively for safety during clinical evaluations of various natures., Conclusion: Clinical translation of non-oncological applications for RGD-based radiopharmaceuticals and other imaging tracers without going through time-consuming extensive development is therefore highly plausible. Graphical abstract.

Prior studies have demonstrated the utility of microRNA assays for predicting some cancer tissue origins, but these assays need to be further optimized for predicting the tissue origins of adenocarcinomas of the liver. We performed microRNA profiling on 195 frozen primary tumor samples using 14 types of tumors that were either adenocarcinomas or differentiated from adenocarcinomas. The 1-nearest neighbor method predicted tissue-of-origin in 33 samples of a test set, with an accuracy of 93.9% at feature selection p values ranging from 10-4 to 10-10. According to binary decision tree analyses, the overexpression of miR-30a and the underexpression of miR-200 family members (miR-200c and miR-141) differentiated intrahepatic cholangiocarcinomas from extrahepatic adenocarcinomas. When binary decision tree analyses were performed using the test set, the prediction accuracy was 84.8%. The overexpression of miR-30a and the reduced expressions of miR-200c, miR-141, and miR-425 could distinguish intrahepatic cholangiocarcinomas from liver metastases from the gastrointestinal tract., Competing Interests: The authors have declared that no competing interests exist.

Highlights: Ultrathin and defect-free graphene ink is prepared through a high-throughput fluid dynamics process, resulting in a high exfoliation yield (53.5%) and a high concentration (47.5 mg mL -1 ). A screen-printed graphene conductor exhibits a high electrical conductivity of 1.49 × 10 4 S m -1 and good mechanical flexibility. An electrochemical sodium ion sensor based on graphene ink exhibits an excellent potentiometric sensing performance in a mechanically bent state. Real-time monitoring of sodium ion concentration in sweat is demonstrated. Conductive inks based on graphene materials have received significant attention for the fabrication of a wide range of printed and flexible devices. However, the application of graphene fillers is limited by their restricted mass production and the low concentration of their suspensions. In this study, a highly concentrated and conductive ink based on defect-free graphene was developed by a scalable fluid dynamics process. A high shear exfoliation and mixing process enabled the production of graphene at a high concentration of 47.5 mg mL -1 for graphene ink. The screen-printed graphene conductor exhibits a high electrical conductivity of 1.49 × 10 4 S m -1 and maintains high conductivity under mechanical bending, compressing, and fatigue tests. Based on the as-prepared graphene ink, a printed electrochemical sodium ion (Na + ) sensor that shows high potentiometric sensing performance was fabricated. Further, by integrating a wireless electronic module, a prototype Na + -sensing watch is demonstrated for the real-time monitoring of the sodium ion concentration in human sweat during the indoor exercise of a volunteer. The scalable and efficient procedure for the preparation of graphene ink presented in this work is very promising for the low-cost, reproducible, and large-scale printing of flexible and wearable electronic devices.

Objectives: Whilst reduced signalling and gene expression related to gamma-aminobutyric acid (GABA) play a role in the presumed pathophysiology of schizophrenia, its origin is unclear. Studying asymptomatic individuals with high genetic liability to schizophrenia (AIs) would provide insights. Therefore, this study aimed to investigate the role of genetic liability in GABAergic dysfunction of schizophrenia by exploring in vivo GABA-A/benzodiazepine receptor (GABAR) availability in AIs., Methods: A total of 10 AIs with multiple relatives diagnosed as schizophrenia and 11 healthy controls underwent [11C]flumazenil positron emission tomography and neurocognitive function tests., Results: There was no significant difference in [11C]flumazenil availability based on the groups. GABAR availability in caudate nuclei had positive correlations with genetic liability of AIs. GABAR availability in caudate nuclei and verbal memory measures of AIs revealed positive correlations. Only the correlation between right caudate and short-term verbal memory survived multiple-comparison correction (p = 0.030)., Conclusions: This study, for the first time, reports correlations between the genetic liability of schizophrenia and GABAR availability. Correlations between [11C]flumazenil binding in caudate of individuals with high genetic liability to schizophrenia suggests that the GABAergic dysfunction may arise from shared genetic factors and also that it may be responsible for cognitive impairment of AIs., (© 2020 John Wiley & Sons Ltd.)

Eosinophils are a myeloid cell subpopulation that mediates type 2 T helper cell immune responses. Unexpectedly, we identified a rapid accumulation of eosinophils in 22 human liver grafts after hepatic transplantation. In contrast, no eosinophils were detectable in healthy liver tissues before transplantation. Studies with two genetic mouse models of eosinophil deficiency and a mouse model of antibody-mediated eosinophil depletion revealed exacerbated liver injury after hepatic ischemia and reperfusion. Adoptive transfer of bone marrow-derived eosinophils normalized liver injury of eosinophil-deficient mice and reduced hepatic ischemia and reperfusion injury in wild-type mice. Mechanistic studies combining genetic and adoptive transfer approaches identified a critical role of suppression of tumorigenicity (ST2)-dependent production of interleukin-13 by eosinophils in the hepatoprotection against ischemia-reperfusion-induced injury. Together, these data provide insight into a mechanism of eosinophil-mediated liver protection that could serve as a therapeutic target to improve outcomes of patients undergoing liver transplantation., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Viral hemorrhagic septicemia virus (VHSV) is a rhabdovirus that causes high mortality in cultured flounder. Naturally occurring VHSV strains vary greatly in virulence. Until now, little has been known about genetic alterations that affect the virulence of VHSV in flounder. We recently reported the full-genome sequences of 18 VHSV strains. In this study, we determined the virulence of these 18 VHSV strains in flounder and then the assessed relationships between differences in the amino acid sequences of the 18 VHSV strains and their virulence to flounder. We identified one amino acid substitution in the phosphoprotein (P) (Pro55-to-Leu substitution in the P protein; PP55L) that is specific to highly virulent strains. This PP55L substitution was maintained stably after 30 cell passages. To investigate the effects of the PP55L substitution on VHSV virulence in flounder, we generated a recombinant VHSV carrying PP55L (rVHSV-P) from rVHSV carrying P55 in the P protein (rVHSV-wild). The rVHSV-P produced high level of viral RNA in cells and showed increased growth in cultured cells and virulence in flounder compared to the rVHSV-wild. In addition, rVHSV-P significantly inhibited the induction of the IFN1 gene in both cells and fish at 6 h post-infection. An RNA-seq analysis confirmed that rVHSV-P infection blocked the induction of several IFN-related genes in virus-infected cells at 6 h post-infection compared to rVHSV-wild. Ectopic expression of PP55L protein resulted in a decrease in IFN induction and an increase in viral RNA synthesis in rVHSV-wild-infected cells. Taken together, our results are the first to identify that the P55L substitution in the P protein enhances VHSV virulence in flounder. The data from this study add to the knowledge of VHSV virulence in flounder and could benefit VHSV surveillance efforts and the generation of a VHSV vaccine., Competing Interests: The authors have declared that no competing interests exist.

Based on a decade of voluntary work and a year of intensive ethnographic fieldwork in an orthodox Jewish care home in London, I demonstrate the ways in which an individual's loss of cognition, language and memory is challenged, rethought and facilitated in everyday life. Drawing on Ingold's idea of dwelling, I examine how loss is constantly negotiated and distributed in ways of becoming that are radically contingent, profoundly relational and potentially generative during an art activity in the context of co-dwelling. I refer to this as dementia-becoming . I suggest a more inclusive understanding of loss as a way of life, constitutive of life, and appreciated as a potential co-creative affordance.

Viral hemorrhagic septicemia virus (VHSV) is a rhabdovirus that causes high mortality in cultured flounder. Viral growth and virulence rely on the ability to inhibit the cellular innate immune response. In this study, we investigated differences in the modulation of innate immune responses of HINAE flounder cells infected with low- and high-virulence VHSV strains at a multiplicity of infection of 1 for 12 h and 24 h and performed RNA sequencing (RNA-seq)-based transcriptome analysis. A total of 193 and 170 innate immune response genes were differentially expressed by the two VHSV strains at 12 and 24 h postinfection (hpi), respectively. Of these, 73 and 77 genes showed more than a twofold change in their expression at 12 and 24 hpi, respectively. Of the genes with more than twofold changes, 22 and 11 genes showed high-virulence VHSV specificity at 12 and 24 hpi, respectively. In particular, IL-16 levels were more than two time higher and CCL20a.3, CCR6b, CCL36.1, Casp8L2, CCR7, and Trim46 levels were more than two times lower in high-virulence-VHSV-infected cells than in low-virulence-VHSV-infected cells at both 12 and 24 hpi. Quantitative PCR (qRT-PCR) confirmed the changes in expression of the ten mRNAs with the most significantly altered expression. This is the first study describing the genome-wide analysis of the innate immune response in VHSV-infected flounder cells, and we have identified innate immune response genes that are specific to a high-virulence VHSV strain. The data from this study can contribute to a greater understanding of the molecular basis of VHSV virulence in flounder.

Hydrogen sulfide (H 2 S) is the third gasotransmitter and is generated endogenously in hypoxic or inflammatory tissues and various cancers. We have recently demonstrated that endogenous H 2 S can be imaged with [ 99m Tc]Tc-gluconate. In the present study, we detected H 2 S generated in hypoxic tissue, both in vitro and in vivo, using [ 99m Tc]Tc-gluconate. In vitro uptake of [ 99m Tc]Tc-gluconate was measured under hypoxic and normoxic conditions, using the colon carcinoma cell line CT26, and was higher in hypoxic cells than that in normoxic cells. An acute hindlimb ischemia-reperfusion model was established in BALB/c mice by exposing the animals to 3 h of ischemia and 3 h of reperfusion prior to in vivo imaging. [ 99m Tc]Tc-gluconate (12.5 MBq) was intravenously injected through the tail vein, and uptake in the lower limb was analyzed by single-photon emission computed tomography/computed tomography (SPECT/CT). SPECT/CT images showed five times higher uptake in the ischemic limb than that in the normal limb. The standard uptake value (SUVmean) of the ischemic limb was 0.39 ± 0.03, while that of the normal limb was 0.07 ± 0.01. [ 99m Tc]Tc-gluconate is a novel imaging agent that can be used both in vitro and in vivo for the detection of endogenous H 2 S generated in hypoxic tissue.

In the present study, we demonstrated that borage (Borago officinalis L.) seed oil subjected to immobilized lipase pretreatment are enriched with linoleic acid (LNA, 18:2n-6), γ-linolenic acid (GLA, 18:3n-6), and oleic acid (OLA, 18:1n-9). We further showed that lipase-treated borage oil (LT-BOL) regulates the activity and degradation of tyrosinase, an important enzyme implicated in the synthesis of melanin in murine melanocytes, B16F10. LT-BOL and its free fatty acid components reduced the levels of melanin and tyrosinase in melanocytes with GLA exerting similar or stronger effects compared with LNA and OLA. The brightening efficacy of LT-BOL on melanin metabolism in humans was tested by an 8-week, double-blind, randomized clinical trial, which enrolled 21 Korean female adults (mean age 48.57 ± 3.28). Visual evaluation showed that cream containing 1% LT-BOL significantly decreased (p < 0.05) melasma on the treated skin area after 6 and 8 weeks. The analysis of the skin brightness using Chromameter CR-400 confirmed that the brightness of the treated area was significantly increased (p < 0.01) after 4, 6, and 8 weeks. Together, our results suggest that LT-BOL may be suitable as a natural skin whitening cosmeceutical product., (© 2020 AOCS.)

Background: Recently, beneficial roles of ginsenoside F2 (GF2), a minor constituent of Panax ginseng , have been demonstrated in diverse inflammatory diseases. However, its roles in alcoholic liver inflammation and injury have not been clearly understood. Here, we investigated the underlying mechanism by which GF2 ameliorated alcoholic liver injury., Methods: To induce alcoholic liver injury, C57BL/6J wild type (WT) or interleukin (IL)-10 knockout (KO) mice were orally administered with ethanol (3 g/kg) or ethanol-containing GF2 (50 mg/kg) for 2 wk. Liver injury and infiltration of macrophages and neutrophils were evaluated by serum biochemistry and immunohistochemistry, respectively. The changes of hepatic immune cells were assessed by flow cytometry and polymerase chain reaction analysis. In vitro differentiation of naïve T cells was performed., Results: GF2 treatment significantly attenuated alcoholic liver injury, in which infiltrations of inflammatory macrophages and neutrophils were decreased. Moreover, the frequencies of Foxp3 + regulatory T cells (Tregs) increased but IL-17-producing T (Th17) cells decreased in GF2-treated mice compared to controls. Furthermore, the mRNA expression of IL-10 and Foxp3 was significantly increased, whereas IL-17 mRNA expression was suppressed in GF2-treated mice. However, these beneficial roles of GF2 were not observed in GF2-treated IL-10 KO mice, suggesting a critical role of IL-10. Similarly, GF2 treatment suppressed differentiation of naïve T cells into Th17 cells by inhibiting RORγt expression and stimulating Foxp3 expression., Conclusion: The present study suggests that GF2 treatment attenuates alcoholic liver injury by increasing IL-10 expression and Tregs and decreasing IL-17 expression and Th17 cells., Competing Interests: All authors have no conflicts of interest to declare., (© 2020 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)

Prosaposin (PSAP) is a precursor of saposin (SAP), which is present in lysosomal and secreted proteins. PSAP is a member of the SAP-like protein families, which comprise multifunctional proteins. In particular, their antimicrobial activity has been reported. We identified PSAP-like (PsPSAPL) sequences from starry flounder and analysed their expression and antimicrobial activity based on cDNA and amino acid sequences. PsPSAPL showed conservation of three saposin B type domains at high levels, and PsPSAPL mRNA was relatively abundantly distributed in the brain and gills of healthy starry founders. PsPSAPL mRNA showed significant expression changes in response to viral haemorrhagic septicaemia virus and Streptococcus parauberis. Synthetic peptides (PsPSAPL-1 and -2), prepared based on amino acid sequences, were used to confirm as well as analyse the antimicrobial activity against bacteria and parasites. Consequently, PsPSAPL-1 and -2 were found to significantly inhibit the growth of various bacteria and kill the Miamiensis avidus. In addition, bacterial biofilm formation was significantly inhibited. Safety was also confirmed by analysing cell haemolysis. These results indicate the immunological function of PsPSAP and the potential antimicrobial activity of the AMPs PsPSAPL-1 and -2., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The noninvasive early detection of biomarkers for Alzheimer's disease (AD) is essential for the development of specific treatment strategies. This paper proposes an advanced method for fabricating highly ordered and flexible nanopillar-based electrochemical biosensors by the combination of soft/photolithography and metal evaporation. The nanopillar array (NPA) exhibits high surface area containing 1500 nm height and 500 nm diameter with 3:1 ratio. In regard with physical properties of polyurethane (PU) substrate, the developed NPA is sustainable and durable to external pressure such as bending and twisting. To manipulate the NPA surface to biocompatible, the gold was uniformly deposited on the PU substrate. The thiol chemistry which is stably modified on the gold surface as a form of self-assembled monolayer was employed for fabricating the NPA as a biocompatible chip by covalently immobilize the antibodies. The proposed nanopillar-based immunoelectrochemical biosensor exhibited good and stable electrochemical performance in β-amyloid (Aβ) detection. Moreover, we successfully confirmed the performance of the as-developed sensor using the artificial injection of Aβ in human tear, with sensitivity of 0.14 ng/mL and high reproducibility (as a standard deviation below 10%). Our findings show that the developed nanopillar-based sensor exhibits reliable electrochemical characteristics and prove its potential for application as a biosensor platform for testing at the point of care.