Synthetic ShK-like Peptide from the Jellyfish Nemopilema nomurai Has Human Voltage-Gated Potassium-Channel-Blocking Activity.

We identified a new human voltage-gated potassium channel blocker, NnK-1, in the jellyfish Nemopilema nomurai based on its genomic information. The gene sequence encoding NnK-1 contains 5408 base pairs, with five introns and six exons. The coding sequence of the NnK-1 precursor is 894 nucleotides long and encodes 297 amino acids containing five presumptive ShK-like peptides. An electrophysiological assay demonstrated that the fifth peptide, NnK-1, which was chemically synthesized, is an effective blocker of hKv1.3, hKv1.4, and hKv1.5. Multiple-sequence alignment with cnidarian Shk-like peptides, which have Kv1.3-blocking activity, revealed that three residues (3Asp, 25Lys, and 34Thr) of NnK-1, together with six cysteine residues, were conserved. Therefore, we hypothesized that these three residues are crucial for the binding of the toxin to voltage-gated potassium channels. This notion was confirmed by an electrophysiological assay with a synthetic peptide (NnK-1 mu) where these three peptides were substituted with 3Glu, 25Arg, and 34Met. In conclusion, we successfully identified and characterized a new voltage-gated potassium channel blocker in jellyfish that interacts with three different voltage-gated potassium channels. A peptide that interacts with multiple voltage-gated potassium channels has many therapeutic applications in various physiological and pathophysiological contexts.

Ghrelin Represses Thymic Stromal Lymphopoietin Gene Expression through Activation of Glucocorticoid Receptor and Protein Kinase C Delta in Inflamed Skin Keratinocytes.

Ghrelin, a peptide hormone secreted from enteroendocrine cells of the gastrointestinal tract, has anti-inflammatory activity in skin diseases, including dermatitis and psoriasis. However, the molecular mechanism underlying the beneficial effect of ghrelin on skin inflammation is not clear. In this study, we found that ghrelin alleviates atopic dermatitis (AD)-phenotypes through suppression of thymic stromal lymphopoietin (TSLP) gene activation. Knockdown or antagonist treatment of growth hormone secretagogue receptor 1a (GHSR1a), the receptor for ghrelin, suppressed ghrelin-induced alleviation of AD-like phenotypes and suppression of TSLP gene activation. We further found that ghrelin induces activation of the glucocorticoid receptor (GR), leading to the binding of GR with histone deacetylase 3 (HDAC3) and nuclear receptor corepressor (NCoR) NCoR corepressor to negative glucocorticoid response element (nGRE) on the TSLP gene promoter. In addition, ghrelin-induced protein kinase C δ (PKCδ)-mediated phosphorylation of p300 at serine 89 (S89), which decreased the acetylation and DNA binding activity of nuclear factor- κB (NF-κB) p65 to the TSLP gene promoter. Knockdown of PKCδ abolished ghrelin-induced suppression of TSLP gene activation. Our study suggests that ghrelin may help to reduce skin inflammation through GR and PKCδ-p300-NF-κB-mediated suppression of TSLP gene activation.

Fluoxetine in the environment may interfere with the neurotransmission or endocrine systems of aquatic animals.

Antidepressants are extensively used to treat the symptoms of depression in humans, and the environmentally discharged drugs potentially threaten aquatic organisms. In this study, the acute toxic effects of fluoxetine (FLX) were investigated in two aquatic organisms, the freshwater polyp (Hydra magnipapillata) and Javanese medaka (Oryzias javanicus). The median lethal concentration (LC50) of FLX in H. magnipapillata was 3.678, 3.082, and 2.901 mg/L after 24, 48, and 72 h, respectively. Morphological observations of the FLX-exposed H. magnipapillata showed that 1.5 mg/L FLX induced the contraction of the tentacles and body column. The LC50 of FLX in O. javanicus was 2.046, 1.936, 1.532, and 1.237 mg/L after 24, 48, 72, and 96 h, respectively. Observation of the behavior of the FLX-exposed fish showed that FLX reduced their swimming performance at a minimum concentration of 10 µg/L. The half-maximal effective concentration (EC50) of FLX for swimming behavior in O. javanicus was 0.135, 0.108, and 0.011 mg/L after 12, 24, and 96 h, respectively. Transcriptomic analyses indicated that FLX affects various physiological and metabolic processes in both species. FLX exposure induced oxidative stress, reproductive deficiency, abnormal pattern formation, DNA damage, and neurotransmission disturbance in H. magnipapillata, whereas it adversely affected O. javanicus by inducing oxidative stress, DNA damage, endoplasmic reticulum stress, and mRNA instability. Neurotransmission-based behavioral changes and endocrine disruption were strongly suspected in the FLX-exposed fish. These results suggest that FLX affects the behavior and metabolic regulation of aquatic organisms.

Identification of a novel anti-apoptotic E3 ubiquitin ligase that ubiquitinates antagonists of inhibitor of apoptosis proteins SMAC, HtrA2, and ARTS.

Identification of new anti-apoptotic genes is important for understanding the molecular mechanisms underlying apoptosis and tumorigenesis. The present study identified a novel anti-apoptotic gene named AREL1, which encodes a HECT (homologous to E6-AP carboxyl terminus) family E3 ubiquitin ligase. AREL1 interacted with and ubiquitinated IAP antagonists such as SMAC, HtrA2, and ARTS. However, AREL1 was cytosolic and did not localize to nuclei or mitochondria. The interactions between AREL1 and the IAP antagonists were specific for apoptosis-stimulated cells, in which the IAP antagonists were released into the cytosol from mitochondria. Furthermore, the ubiquitination and degradation of SMAC, HtrA2, and ARTS were significantly enhanced in AREL1-expressing cells following apoptotic stimulation, indicating that AREL1 binds to and ubiquitinates cytosolic but not mitochondria-associated forms of IAP antagonists. Furthermore, the anti-apoptotic role of AREL1-mediated degradation of SMAC, HtrA2, and ARTS was shown by simultaneous knockdown of three IAP antagonists, which caused the inhibition of caspase-3 cleavage, XIAP degradation, and induction of apoptosis. Therefore, the present study suggests that AREL1-mediated ubiquitination and degradation of cytosolic forms of three IAP antagonists plays an important role in the regulation of apoptosis.

Improving Prenatal Diagnosis Precision for Congenital Clubfoot by Using Three-Dimensional Ultrasonography.

Prenatal diagnosis of clubfoot traditionally relied on two-dimensional ultrasonography. To enhance diagnosis and predict postnatal outcomes, we examined the parameters that differentiate pathological clubfoot using three-dimensional ultrasonography. In our retrospective study, we examined the findings of prenatal ultrasound and the postnatal outcomes of pregnancies with suspected congenital clubfoot between 2018 and 2021. Based on the three-dimensional perspective, we measured the angles of varus, equinus, calcaneopedal block, and forefoot adduction and compared the sonographic variables between the postnatal treated and non-treated groups. We evaluated 31 pregnancies (47 feet) with suspected clubfoot using three-dimensional ultrasonography. After delivery, a total of 37 feet (78.7%) underwent treatment involving serial casting only or additional Achilles tenotomy. The treated group showed significantly greater hindfoot varus deviation (60.5° vs. 46.6°, p = 0.026) and calcaneopedal block deviation (65.6° vs. 26.6°, p < 0.05) compared to the non-treated group. The calcaneopedal block had an area under the curve of 0.98 with a diagnostic threshold of 46.2 degrees (sensitivity of 97%, specificity of 90%, positive predictive value of 97%, and negative predictive value of 90%). During prenatal evaluation of clubfoot using three-dimensional ultrasonography, the calcaneopedal block deviation has the potential to predict postnatal treatment.

Topical Nanoliposomal Collagen Delivery for Targeted Fibril Formation by Electrical Stimulation.

Collagen is a complex, large protein molecule that presents a challenge in delivering it to the skin due to its size and intricate structure. However, conventional collagen delivery methods are either invasive or may affect the protein's structural integrity. This study introduces a novel approach involving the encapsulation of collagen monomers within zwitterionic nanoliposomes, termed Lip-Cols, and the controlled formation of collagen fibrils through electric fields (EF) stimulation. The results reveal the self-assembly process of Lip-Cols through electroporation and a pH gradient change uniquely triggered by EF, leading to the alignment and aggregation of Lip-Cols on the electrode interface. Notably, Lip-Cols exhibit the capability to direct the orientation of collagen fibrils within human dermal fibroblasts. In conjunction with EF, Lip-Cols can deliver collagen into the dermal layer and increase the collagen amount in the skin. The findings provide novel insights into the directed formation of collagen fibrils via electrical stimulation and the potential of Lip-Cols as a non-invasive drug delivery system for anti-aging applications.

Long-term dispersion stability and adhesion promotion of aqueous Cu nano-ink for flexible printed electronics.

Aqueous Cu nanoparticles are synthesized using a reducing agent and surface capping molecule which prevents the interparticular agglomeration and surface oxidation. Aqueous conductive nano ink is prepared using the resulting Cu nanoparticles and conductive Cu layers are prepared via a wet coating process. The conductive Cu layers, metalized by annealing at 300 degrees C under vacuum atmosphere, exhibit excellent electrical resistivity, showing values as low as 12 microomega cm. The long-term dispersion stability for three months is monitored through an investigation on the rheological behavior of the conductive nano ink and the resistivity variation of the conductive Cu layer. The adhesion property of the conductive Cu layer is dramatically improved when using a primer-treated polyimide film, whereas the conductive Cu layer completely peels off on a pristine polyimide film. The epoxy-contained primer plays a critical role as an intermediary between the aqueous Cu nano ink and the polyimide film.

Lubricant skin on diverse biomaterials with complex shapes via polydopamine-mediated surface functionalization for biomedical applications.

Implantable biomedical devices require an anti-biofouling, mechanically robust, low friction surface for a prolonged lifespan and improved performance. However, there exist no methods that could provide uniform and effective coatings for medical devices with complex shapes and materials to prevent immune-related side effects and thrombosis when they encounter biological tissues. Here, we report a lubricant skin (L-skin), a coating method based on the application of thin layers of bio-adhesive and lubricant-swellable perfluoropolymer that impart anti-biofouling, frictionless, robust, and heat-mediated self-healing properties. We demonstrate biocompatible, mechanically robust, and sterilization-safe L-skin in applications of bioprinting, microfluidics, catheter, and long and narrow medical tubing. We envision that diverse applications of L-skin improve device longevity, as well as anti-biofouling attributes in biomedical devices with complex shapes and material compositions.

3D printing of mechanically tough and self-healing hydrogels with carbon nanotube fillers.

Hydrogels have the potential to play a crucial role in bioelectronics, as they share many properties with human tissues. However, to effectively bridge the gap between electronics and biological systems, hydrogels must possess multiple functionalities, including toughness, stretchability, self-healing ability, three-dimensional (3D) printability, and electrical conductivity. Fabricating such tough and self-healing materials has been reported, but it still remains a challenge to fulfill all of those features, and in particular, 3D printing of hydrogel is in the early stage of the research. In this paper, we present a 3D printable, tough, and self-healing multi-functional hydrogel in one platform made from a blend of poly(vinyl alcohol) (PVA), tannic acid (TA), and poly(acrylic acid) (PAA) hydrogel ink (PVA/TA/PAA hydrogel ink). Based on a reversible hydrogen-bond (H-bond)-based double network, the developed 3D printable hydrogel ink showed excellent printability via shear-thinning behavior, allowing high printing resolution (~100 µm) and successful fabrication of 3D-printed structure by layer-by-layer printing. Moreover, the PVA/TA/PAA hydrogel ink exhibited high toughness (tensile loading of up to ~45.6 kPa), stretchability (elongation of approximately 650%), tissue-like Young's modulus (~15 kPa), and self-healing ability within 5 min. Furthermore, carbon nanotube (CNT) fillers were successfully added to enhance the electrical conductivity of the hydrogel. We confirmed the practicality of the hydrogel inks for bioelectronics by demonstrating biocompatibility, tissue adhesiveness, and strain sensing ability through PVA/TA/PAA/CNT hydrogel ink.

Rapid discovery and classification of inhibitors of coronavirus infection by pseudovirus screen and amplified luminescence proximity homogeneous assay.

To identify potent antiviral compounds, we introduced a high-throughput screen platform that can rapidly classify hit compounds according to their target. In our platform, we performed a compound screen using a lentivirus-based pseudovirus presenting a spike protein of coronavirus, and we evaluated the hit compounds using an amplified luminescence proximity homogeneous assay (alpha) test with purified host receptor protein and the receptor binding domain of the viral spike. With our screen platform, we were able to identify both spike-specific compounds (class I) and broad-spectrum antiviral compounds (class II). Among the hit compounds, thiosemicarbazide was identified to be selective to the interaction between the viral spike and its host cell receptor, and we further optimized the binding potency of thiosemicarbazide through modification of the pyridine group. Among the class II compounds, we found raloxifene and amiodarone to be highly potent against human coronaviruses including Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and SARS-CoV-2. In particular, using analogs of the benzothiophene moiety, which is also present in raloxifene, we have identified benzothiophene as a novel structural scaffold for broad-spectrum antivirals. This work highlights the strong utility of our screen platform using a pseudovirus assay and an alpha test for rapid identification of potential antiviral compounds and their mechanism of action, which can lead to the accelerated development of therapeutics against newly emerging viral infections.

Chromosome-Level Genome Assembly of the Butter Clam Saxidomus purpuratus.

Herein, we provide the first whole-genome sequence of the purple butter clam (Saxidomus purpuratus), an economically important bivalve shellfish. Specifically, we sequenced and de novo assembled the genome of Sa. purpuratus based on PromethION long reads and Hi-C data. The 978-Mb genome of Sa. purpuratus comprises 19 chromosomes with 36,591 predicted protein-coding genes. The N50 length of Sa. purpuratus genome is 52 Mb, showing the highest continuous assembly among bivalve genomes. The Benchmarking by Universal Single-Copy Orthologs assessment indicated that 95.07% of complete metazoan universal single-copy orthologs (n = 954) were present in the assembly. Approximately 51% of Sa. purpuratus genome comprises repetitive sequences. Based on the high-quality Sa. purpuratus genome, we resolved half of the immune-associated genes, namely, scavenger receptor (SR) proteins, which are collinear to those in the closely related Cyclina sinensis genome. This finding suggested a high degree of conservation among immune-associated genes. Twenty-two (19%) SR proteins are tandemly duplicated in Sa. purpuratus genome, suggesting putative convergence evolution. Overall, Sa. purpuratus genome provides a new resource for the discovery of economically important traits and immune-response genes.

Printable Self-Activated Liquid Metal Stretchable Conductors from Polyvinylpyrrolidone-Functionalized Eutectic Gallium Indium Composites.

Stretchable electronic circuits are critical in a variety of next-generation electronics applications, including soft robots, wearable technologies, and biomedical applications. To date, printable composite conductors comprising various types of conductive fillers have been suggested to achieve high electrical conductance and excellent stretchability. Among them, liquid metal particles have been considered as a viable candidate filler that can meet the necessary prerequisites. However, a mechanical activation process is needed to generate interconnected liquid channels inside elastomeric polymers. In this study, we have developed a chemical strategy of surface-functionalizing liquid metal particles to eliminate the necessity of additional mechanical activation processes. We found that the characteristic conformations of the polyvinylpyrrolidone surrounding eutectic gallium indium particles are highly dependent on the molecular weight of polyvinylpyrrolidone. By virtue of the specific chemical roles of polyvinylpyrrolidone, the as-printed composite layers are highly conductive and stretchable, exhibiting an electrical conductivity approaching 8372 S/cm at 100% strain and an invariant resistance change of 0.92 even at 75% strain after a 60,000 cycle test. The results demonstrate that the self-activated liquid metal-based composite conductors are applicable to traditional stretchable electronics, healable stretchable electronics, and shape-morphable applications.

Comparative Genome and Evolution Analyses of an Endangered Stony Coral Species Dendrophyllia cribrosa Near Dokdo Islands in the East Sea.

Stony corals often harbor intracellular photosynthetic dinoflagellate algae that receive dissolved inorganic nutrients. However, Dendrophyllia cribrosa is a nonsymbiotic stony coral distributed in the western Pacific. We assembled a chromosome-level D. cribrosa genome using PacBio and Hi-C technologies. The final assembly was 625 Mb, distributed on 14 chromosomes, and contained 30,493 protein-coding genes. The Benchmarking Universal Single-Copy Orthologs analysis revealed a percentage of 96.8 of the metazoan genome. A comparative phylogenetic analysis revealed that D. cribrosa, which lacks symbionts, evolved to acquire cellular energy by expanding genes related to acyl-CoA metabolism and carbohydrate transporters. This species also has expanded immune-related genes involved in the receptor protein tyrosine kinase signaling pathway. In addition, we observed a specific expansion of calcification genes, such as coral acid-rich proteins and carbonic anhydrase, in D. cribrosa. This high-quality reference genome and comparative analysis provides insights into the ecology and evolution of nonsymbiotic stony corals.

Three-Dimensional Multistack-Printed, Self-Powered Flexible Pressure Sensor Arrays: Piezoelectric Composites with Chemically Anchored Heterogeneous Interfaces.

Recently, the development of pressure sensor devices composed of mechanically flexible materials has gained a tremendous attention for emerging wearable electronics applications. Compared with various sensing materials, piezoelectric composite materials provide a characteristic advantage of enabling energy unit-free integration of sensor compartments. In this study, we develop a new chemical method of synthesizing highly functioning piezoelectric composite materials with electrostatically reinforced heterogeneous interfaces to improve the voltage output signal in all-printed sensor arrays. The surfaces of piezoelectric oxide nanoparticles are decorated subsequently with a cationic polyelectrolyte, polyethyleneimine, and a tri-block copolymer, styrene-ethylene/butylene-styrene grafted with maleic anhydride. To elucidate the factors determining the performance of pressure sensor devices, both the electrical properties and piezoelectric characteristics are investigated comprehensively for various compositional composite materials prepared from chemical and physical rubbers. The resulting device exhibits a sensitivity of 0.28 V·kPa-1 with a linear increment of output voltage in a pressure range up to 30 kPa. It is also demonstrated that the all-printed sensor array is fabricated successfully by a multistack-printing process of conductive, insulating, and piezoelectric composite materials in an additive manufacturing fashion.

The complete mitochondrial genome of a Dokdo shrimp, Lebbeus groenlandicus.

Lebbeus groenlandicus is a shrimp species indigenous to the Dokdo islands in the East Sea of Korea. We report the 17,399 bp mitochondrial genome (mitogenome) of the species that consists of 13 protein-coding genes, 22 transfer RNAs (tRNAs), 2 ribosomal RNAs (rRNAs), and a control region (CR). A maximum-likelihood tree, constructed with 18 prawn and 45 shrimp mitogenomes, confirmed that L. groenlandicus occupies the most basal position within the Caridea infra-order and is closely related to Pandalidae shrimps.

Printable Thick Copper Conductors from Optically Modulated Multidimensional Particle Mixtures.

Printing techniques that enable the formation of arbitrarily designed architectures have been implemented in various research fields owing to their characteristic advantages in processing over other techniques. In particular, low-cost, printable conductors are of paramount importance in the production of highly functioning printed electronics. Among various candidates, copper (Cu) particle-based printable fluid has been regarded as the most promising constituent material in conjunction with the use of the flash-light-sintering (FLS) process in air. In this study, we synthesized surface-oxidation-suppressed Cu nanoparticles, sub-micronparticles, and flakes to regulate the optical absorption characteristics in FLS-processed, Cu-based printed conductors. Our results revealed clearly that the critical issues in FLS-processed conductors, namely, undesirable crack formation and a limitation of thickness, are resolved by adjusting the optical behaviors of particulate layers by variation of the composition of multidimensional mixture particles. It is suggested that crack-free, 13.2 µm thick printed Cu conductors can be generated with a resistivity of 11.4 µΩ cm by printing and FLS processes in air. The proposed alternative approach is demonstrated with electrical circuits comprising electrodes and interconnections.

Three-dimensionally printed pressure sensor arrays from hysteresis-less stretchable piezoresistive composites.

In this study, we formulate three-dimensionally (3D) printable composite pastes employing electrostatically assembled-hybrid carbon and a polystyrene-polyisoprene-polystyrene tri-block copolymer elastomer for the fabrication of multi-stack printed piezoresistive pressure sensor arrays. To address a critical drawback of piezoresistive composite materials, we have developed a previously unrecognized strategy of incorporating a non-ionic amphiphilic surfactant, sorbitan trioleate, into composite materials. It is revealed that the surfactant with an appropriate amphiphilic property, represented by the hydrophilic-lipophilic balance (HLB) index of 1.8, allows for a reversible piezoresistive characteristic under a wide pressure range up to 30 kPa as well as a significant reduction of elastomer viscoelastic behavior. The 3D-printed pressure sensor arrays exhibit a sensitivity of 0.31 kPa-1 in a linear trend, and it is demonstrated successfully that the position-addressable array device is capable of spatially detecting objects up to a pressure level of 22.1 kPa.

Three-Dimensionally Printed Stretchable Conductors from Surfactant-Mediated Composite Pastes.

A stretchable conductor is a critical prerequisite to achieve various forms of stretchable electronics. In particular, directly printable stretchable conductors have gathered considerable attention with recent growing interest in a variety of large-area, deformable electronics. In this study, we have developed a chemical pathway of incorporating a surfactant with a moderate hydrophilic-lipophilic balance in formulating composite pastes for printed stretchable conductors, with a possibility of a vertically stackable, three-dimensional printing process. We demonstrate that the addition of a nonionic surfactant, sorbitane monooleate (commonly called SPAN 80) in Ag flake-based composite pastes, allows a critical reduction in resistance variation under an external strain. The four-layer stacked, surfactant-added composite conductors show a resistance variation of merely 1.6 at a strain of 0.6 and excellent cycling durability over 1000 cycles. The effectiveness of the methods suggested in this study is demonstrated with basic light-emitting diode circuits and the thermal heating characteristics of stretchable conductors.

The Draft Genome of an Octocoral, Dendronephthya gigantea.

Coral reefs composed of stony corals are threatened by global marine environmental changes. However, soft coral communities of octocorallian species, appear more resilient. The genomes of several cnidarians species have been published, including from stony corals, sea anemones, and hydra. To fill the phylogenetic gap for octocoral species of cnidarians, we sequenced the octocoral, Dendronephthya gigantea, a nonsymbiotic soft coral, commonly known as the carnation coral. The D. gigantea genome size is ∼276 Mb. A high-quality genome assembly was constructed from PacBio long reads (29.85 Gb with 108× coverage) and Illumina short paired-end reads (35.54 Gb with 128× coverage) resulting in the highest N50 value (1.4 Mb) reported thus far among cnidarian genomes. About 12% of the genome is repetitive elements and contained 28,879 predicted protein-coding genes. This gene set is composed of 94% complete BUSCO ortholog benchmark genes, which is the second highest value among the cnidarians, indicating high quality. Based on molecular phylogenetic analysis, octocoral and hexacoral divergence times were estimated at 544 MYA. There is a clear difference in Hox gene composition between these species: unlike hexacorals, the Antp superclass Evx gene was absent in D. gigantea. Here, we present the first genome assembly of a nonsymbiotic octocoral, D. gigantea to aid in the comparative genomic analysis of cnidarians, including stony and soft corals, both symbiotic and nonsymbiotic. The D. gigantea genome may also provide clues to mechanisms of differential coping between the soft and stony corals in response to scenarios of global warming.

3D-printed origami electronics using percolative conductors.

Recently, three-dimensional (3D) printing has garnered tremendous amounts of attention in various applications. In this study, we suggest a facile means of creating 3D-printed foldable electrodes on paper via the direct printing of composite pastes consisting of conductive fillers and a thermoplastic elastomer. The 3D-printability of the prepared composite pastes is investigated depending on the rheological properties. It is revealed that the composite paste with a high storage modulus would enable the formation of highly conductive features with a resistance of 0.4 Ω cm-1 on three-dimensional paper structures. The mechanical bending/folding stability levels of the printed electrodes are evaluated to judge the possibility of realizing 3D-printed origami electronics. The resistance is changed slightly with a normalized resistance value of 2.3, when the printed electrodes are folded with a folding angle of 150°. It is demonstrated that the 3D-printed composite electrodes are applicable to various origami electronics, including electrical circuits, strain sensors and electrochemical sensors.