Do red tide events promote an increase in zooplankton biodiversity?

Red tides occurring off the southern coast of Korea impact the marine ecosystem and aquaculture industries. Zooplankton are crucial in the food web, connecting primary producers to higher predators and interact diversely with red tide organisms. This study explores dynamics of the zooplankton community over seven years including three red tide and four non-red tide years in Tongyeong using metabarcoding. In non-red tide years, zooplankton diversity showed typical seasonal patterns, increasing from June to early October. However, during red tide years, diversity remained high, with a shift in species composition-decreased Copepoda and increased Branchiopoda, Echinodermata, Malacostraca, and Annelida. Diversity indices were significantly higher in red tide years across all periods except for the richness in "after" that showed an insignificant higher value. The differences in zooplankton assemblages across periods were influenced by surface temperatures and the density of the red tide-causing alga Margalefidinium polykrikoides. Eight species emerged as indicator species and showed direct correlations with M. polykrikoides and among them, seven species were indicator species for red tide occurrence years. The ecological characteristics of M. polykrikoides blooms and their recurrent occurrences over several decades suggest that zooplankton may adapt to the toxins and use these blooms as spawning cues. Overall, this study provides comprehensive understanding on changes in zooplankton communities during red tide events, offering novel insights into their ecology.

The Role and Future Tasks of the National Assembly Suicide Prevention Forum - Focusing on the Legislative Content of Suicide Prevention Laws.

OBJECTIVE: In South Korea, there were 12,906 suicides in 2022. This number is 4.7 times higher than the number of traffic accident deaths-i.e., 2,753-in the same year. Suicide is so serious that it is the fifth leading cause of death in South Korea. We would like to discuss how the National Assembly Suicide Prevention Forum was established, what role it has played in preventing suicide, and what role it should play in the future. METHODS: We will look into the representatives and lawmakers who made up the National Assembly Suicide Prevention and summarize the topics of seminars conducted in each period. RESULTS: Through the establishment of the National Assembly Suicide Prevention Forum in 2018, which is referred to hereafter as the "Forum," various efforts have been made to garner the attention of government ministries, which has led to an increase of 6.7 times in the budget for suicide prevention compared to 2017. With the launch of the forum, private organizations that had previously been working independently in their own fields were able to come together and speak with a unified voice. The formation of the Forum has brought the issue of suicide, which had previously been buried in the dark corners of our society, to the forefront as a social problem, and it has provided an impetus for seeking solutions. CONCLUSION: In the 22nd National Assembly of South Korea, the National Assembly Suicide Prevention Forum is expected to play a more prominent role, which is expected to lead to substantial achievements in suicide prevention.

Anticancer Evaluation of Novel Benzofuran-Indole Hybrids as Epidermal Growth Factor Receptor Inhibitors against Non-Small-Cell Lung Cancer Cells.

The epidermal growth factor receptor (EGFR), also known as ErbB1 and HER1, belongs to the receptor tyrosine kinase family. EGFR serves as the primary driver in non-small-cell lung cancer (NSCLC) and is a promising therapeutic target for NSCLC. In this study, we synthesized a novel chemical library based on a benzofuran-indole hybrid scaffold and identified 8aa as a potent and selective EGFR inhibitor. Interestingly, 8aa not only showed selective anticancer effects against NSCLC cell lines, PC9, and A549, but it also showed significant inhibitory effects against the double mutant L858R/T790M EGFR, which frequently occurs in NSCLC. In addition, in PC9 and A549 cells, 8aa potently blocked the EGFR signaling pathway, cell viability, and cell migration. These findings suggest that 8aa, a benzofuran-indole hybrid derivative, is a novel EGFR inhibitor that may be a potential candidate for the treatment of NSCLC patients with EGFR mutations.

A Study on the Interoperability Technology of Digital Identification Based on WACI Protocol with Multiparty Distributed Signature.

In digital identity authentication, credentials are typically stored in a digital wallet and authenticated through a single key-based signature and public key verification. However, ensuring compatibility between systems and credentials can be challenging and the existing architecture can create a single point of failure, which can hinder system stability and prevent data interchange. To address this problem, we propose a multiparty distributed signature structure using FROST, a Schnorr signature-based threshold signature algorithm, applied to the WACI protocol framework for credential interaction. This approach eliminates a single point of failure and secures the signer's anonymity. Additionally, by following standard interoperability protocol procedures, we can ensure interoperability during the exchange of digital wallets and credentials. This paper presents a method that combines a multiparty distributed signature algorithm and an interoperability protocol, and discusses the implementation results.

p21-activated kinase 4 inhibition protects against liver ischemia/reperfusion injury: Role of nuclear factor erythroid 2-related factor 2 phosphorylation.

BACKGROUND AND AIMS: p21-activated kinase 4 (PAK4), an oncogenic protein, has emerged as a promising target for anticancer drug development. Its role in oxidative stress conditions, however, remains elusive. We investigated the effects of PAK4 signaling on hepatic ischemia/reperfusion (I/R) injury. APPROACH AND RESULTS: Hepatocyte- and myeloid-specific Pak4 knockout (KO) mice and their littermate controls were subjected to a partial hepatic I/R (HIR) injury. We manipulated the catalytic activity of PAK4, either through genetic engineering (gene knockout, overexpression of wild-type [WT] or dominant-negative kinase) or pharmacological inhibitor, coupled with a readout of nuclear factor erythroid 2-related factor 2 (Nrf2) activity, to test the potential function of PAK4 on HIR injury. PAK4 expression was markedly up-regulated in liver during HIR injury in mice and humans. Deletion of PAK4 in hepatocytes, but not in myeloid cells, ameliorated liver damages, as demonstrated in the decrease in hepatocellular necrosis and inflammatory responses. Conversely, the forced expression of WT PAK4 aggravated the pathological changes. PAK4 directly phosphorylated Nrf2 at T369, and it led to its nuclear export and proteasomal degradation, all of which impaired antioxidant responses in hepatocytes. Nrf2 silencing in liver abolished the protective effects of PAK4 deficiency. A PAK4 inhibitor protected mice from HIR injury. CONCLUSIONS: PAK4 phosphorylates Nrf2 and suppresses its transcriptional activity. Genetic or pharmacological suppression of PAK4 alleviates HIR injury. Thus, PAK4 inhibition may represent a promising intervention against I/R-induced liver injury.

Zooplankton diversity monitoring strategy for the urban coastal region using metabarcoding analysis.

Marine ecosystems in urban coastal areas are exposed to many risks due to human activity. Thus, long-term and continuous monitoring of zooplankton diversity is necessary. High-throughput DNA metabarcoding has gained recognition as an efficient and highly sensitive approach to accurately describing the species diversity of marine zooplankton assemblages. In this study, we collected 30 zooplankton samples at about 2-week intervals for 1 year. Zooplankton diversity showing a typical four season pattern. Of the "total" and "common" zooplankton, we assigned 267 and 64 taxa. The cluster structure and seasonal diversity pattern were rough when only the "common" zooplankton was used. Our study examined how to maximize the benefits of metabarcoding for monitoring zooplankton diversity in urban coastal areas. The results suggest that to take full advantage of metabarcoding when monitoring a zooplankton community, it is necessary to carefully investigate potential ecosystem threats (non-indigenous species) through sufficient curation rather than disregarding low-abundance operational taxonomic units.

DNA barcoding of brackish and marine water fishes and shellfishes of Sundarbans, the world's largest mangrove ecosystem.

The present study aims to apply a DNA barcoding tool through amplifying two mitochondrial candidate genes i.e., COI and 16S rRNA for accurate identification of fish, aquatic molluscs and crustaceans of Sundarbans mangrove wetland, to build a reference library of fish and shellfishes of this unique ecosystems. A total of 185 mitochondrial COI barcode sequences and 59 partial sequences of the 16S rRNA gene were obtained from 120 genera, 65 families and 21 orders of fish, crustaceans and molluscs. The collected samples were first identified by examining morphometric characteristics and then assessed by DNA barcoding. The COI and 16S rRNA sequences of fishes and crustaceans were clearly discriminated among genera in their phylogenies. The average Kimura two-parameter (K2P) distances of COI barcode sequences within species, genera, and families of fishes are 1.57±0.06%, 15.16±0.23%, and 17.79±0.02%, respectively, and for 16S rRNA sequences, these values are 1.74±.8%, 0.97±.8%, and 4.29±1.3%, respectively. The minimum and maximum K2P distance based divergences in COI sequences of fishes are 0.19% and 36.27%, respectively. In crustaceans, the K2P distances within genera, families, and orders are 1.4±0.03%, 17.73±0.15%, and 22.81±0.02%, respectively and the minimum and maximum divergences are 0.2% and 33.93%, respectively. Additionally, the present study resolves the misidentification of the mud crab species of the Sundarbans as Scylla olivacea which was previously stated as Scylla serrata. In case of molluscs, values of interspecific divergence ranges from 17.43% to 66.3% in the barcoded species. The present study describes the development of a molecular and morphometric cross-referenced inventory of fish and shellfish of the Sundarbans. This inventory will be useful in future biodiversity studies and in forming future conservation plan.

X-ray Crystal Structure-Guided Design and Optimization of 7H-Pyrrolo[2,3-d]pyrimidine-5-carbonitrile Scaffold as a Potent and Orally Active Monopolar Spindle 1 Inhibitor.

Triple-negative breast cancer (TNBC) is an aggressive breast-cancer subtype associated with poor prognosis and high relapse rates. Monopolar spindle 1 kinase (MPS1) is an apical dual-specificity protein kinase that is over-expressed in TNBC. We herein report a highly selective MPS1 inhibitor based on a 7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile scaffold. Our lead optimization was guided by key X-ray crystal structure analysis. In vivo evaluation of candidate (9) is shown to effectively mitigate human TNBC cell proliferation.

A Password Meter without Password Exposure.

To meet password selection criteria of a server, a user occasionally needs to provide multiple choices of password candidates to an on-line password meter, but such user-chosen candidates tend to be derived from the user's previous passwords-the meter may have a high chance to acquire information about a user's passwords employed for various purposes. A third party password metering service may worsen this threat. In this paper, we first explore a new on-line password meter concept that does not necessitate the exposure of user's passwords for evaluating user-chosen password candidates in the server side. Our basic idea is straightforward; to adapt fully homomorphic encryption (FHE) schemes to build such a system but its performance achievement is greatly challenging. Optimization techniques are necessary for performance achievement in practice. We employ various performance enhancement techniques and implement the NIST (National Institute of Standards and Technology) metering method as seminal work in this field. Our experiment results demonstrate that the running time of the proposed meter is around 60 s in a conventional desktop server, expecting better performance in high-end hardware, with an FHE scheme in HElib library where parameters support at least 80-bit security. We believe the proposed method can be further explored and used for a password metering in case that password secrecy is very important-the user's password candidates should not be exposed to the meter and also an internal mechanism of password metering should not be disclosed to users and any other third parties.

Metabarcoding of Fish Larvae in the Merbok River Reveals Species Diversity and Distribution Along its Mangrove Environment.

The Merbok River (north-west of Peninsular Malaysia) is a mangrove estuary that provides habitat for over 100 species of fish, which are economically and ecologically important. Threats such as habitat loss and overfishing are becoming a great concern for fisheries conservation and management. The identification of larval fish in this estuarine system is important to complement information on the adults. This is because the data could inform the spawning behaviour, reproductive biology, selection of nursery grounds and migration route of fish. Such information is invaluable for fisheries and aquatic environmental monitoring, and thus for their conservation and management. However, identifying fish larvae is a challenging task based only on morphology and even traditional DNA barcoding. To address this, DNA metabarcoding was utilised to detect the diversity of fish in the Merbok River. To complete the study, the fish larvae were collected at six sampling sites of the river. The extracted larval DNA was amplified for the Cytochrome Oxidase subunit 1 (COI) and 12S ribosomal RNA (12S rRNA) genes based on the metabarcoding approach using shotgun sequencing on the next-generation sequencing (NGS) Illumina MiSeq platform. Eighty-nine species from 65 genera and 41 families were detected, with Oryzias javanicus, Oryzias dancena, Lutjanus argentimaculatus and Lutjanus malabaricus among the most common species. The lower diversity observed from previous morphological studies is suggested to be mainly due to seasonal variation over the sampling period between the two methods and limited 12S rRNA sequences in current databases. The metabarcode data and a validation Sanger sequencing step using 15 species-specific primer pairs detected three species in common: Oryzias javanicus, Decapterus maruadsi and Pennahia macrocephalus. Several discrepancies observed between the two molecular approaches could be attributed to contaminants during sampling and DNA extraction, which could mask the presence of target species, especially when DNA from the contaminants is more abundant than the target organisms. In conclusion, this rapid and cost-effective identification method using DNA metabarcoding allowed the detection of numerous fish species from bulk larval samples in the Merbok River. This method can be applied to other sites and other organisms of interest.

Effects of Balneotherapy in Jeju Magma-Seawater on Knee Osteoarthritis Model.

Balneotherapy is a common non-pharmacological treatment for osteoarthritis (OA), however, the efficacy is controversial in knee OA. Jeju magma-seawater (JMS) has high contents of various minerals, which has anti-inflammatory and antioxidant properties via an oral route. Thus, we examined the effects of JMS bathing on knee OA and the combination effects with diclofenac sodium as an anti-inflammatory drug. Knee OA was induced by transection of the anterior cruciate ligament and the partial meniscectomy in rat. The rats were administered subcutaneously saline or diclofenac sodium in saline, followed by bathing in thermal distilled water or JMS for 8 weeks. The model represented the characteristic changes of the cartilage degradation, osteophyte formation and synovial inflammation, and the relevant symptoms of the joint swelling and stiffness. However, the JMS bathing reduced the joint thickness and improved the mobility. It also contributed to a well-preserved tissue supported by increases in bone mineral density of the joint and decreases in Mankin scores in the cartilages. The effects involved anti-inflammation, chondroprotection, anti-apoptosis, and chondrogenesis. Overall, the JMS bathing in combination with diclofenac sodium showed a similar trend associated with synergic effects. It suggests that JMS bathing can be promising for a clinical use in knee OA.

Structure, evolution and phylogenetic informativeness of eelpouts (Cottoidei: Zoarcales) mitochondrial control region sequences.

Control region (CR) is a major non-coding domain of mitochondrial DNA in vertebrates which contains the promoters for replication and transcription of mitochondrial genome along with the binding sites for metabolic machinery and, hence, is a vital element for the integrity of mitochondrial genome as a biological replicator. The origin and diversity of structural elements within CR have been intensively studied in recent years with the involvement of new diverse taxa. In this paper, we provide new data on the nucleotide and structural patterns of CR evolution and phylogenetic suitability among eelpouts (Cottoidei: Zoarcales). To achieve this, we carried out a comparative phylogenetic and structural analysis of 29 CR sequences belonging to the long shanny Stichaeus grigorjewi together with nine sequences of other eelpouts taxa representing four families in contrast to mitochondrial protein-coding fragments. The CR organization within S. grigorjewi, as well as in all other eelpouts, is consistent with the common three-domain structure known from most vertebrates. We found a hidden CR variation constrains on the landscape level and a lack of nucleotide saturation. Finally, our results demonstrate the advantage of the length variation in CR sequences for phylogenetic reconstructions among eelpouts.

Molecular basis of maintaining an oxidizing environment under anaerobiosis by soluble fumarate reductase.

Osm1 and Frd1 are soluble fumarate reductases from yeast that are critical for allowing survival under anaerobic conditions. Although they maintain redox balance during anaerobiosis, the underlying mechanism is not understood. Here, we report the crystal structure of a eukaryotic soluble fumarate reductase, which is unique among soluble fumarate reductases as it lacks a heme domain. Structural and enzymatic analyses indicate that Osm1 has a specific binding pocket for flavin molecules, including FAD, FMN, and riboflavin, catalyzing their oxidation while reducing fumarate to succinate. Moreover, ER-resident Osm1 can transfer electrons from the Ero1 FAD cofactor to fumarate either by free FAD or by a direct interaction, allowing de novo disulfide bond formation in the absence of oxygen. We conclude that soluble eukaryotic fumarate reductases can maintain an oxidizing environment under anaerobic conditions, either by oxidizing cellular flavin cofactors or by a direct interaction with flavoenzymes such as Ero1.

Discovery of a novel potent peptide agonist to adiponectin receptor 1.

Activation of adiponectin receptors (AdipoRs) by its natural ligand, adiponectin has been known to be involved in modulating critical metabolic processes such as glucose metabolism and fatty acid oxidation as demonstrated by a number of in vitro and in vivo studies over last two decades. These findings suggest that AdipoRs' agonists could be developed into a potential therapeutic agent for metabolic diseases, such as diabetes mellitus, especially for type II diabetes, a long-term metabolic disorder characterized by high blood sugar, insulin resistance, and relative lack of insulin. Because of limitations in production of biologically active adiponectin, adiponectin-mimetic AdipoRs' agonists have been suggested as alternative ways to expand the opportunity to develop anti-diabetic agents. Based on crystal structure of AdipoR1, we designed AdipoR1's peptide agonists using protein-peptide docking simulation and screened their receptor binding abilities and biological functions via surface plasmon resonance (SPR) and biological analysis. Three candidate peptides, BHD1028, BHD43, and BHD44 were selected and confirmed to activate AdipoR1-mediated signal pathways. In order to enhance the stability and solubility of peptide agonists, candidate peptides were PEGylated. PEGylated BHD1028 exhibited its biological activity at nano-molar concentration and could be a potential therapeutic agent for the treatment of diabetes. Also, SPR and virtual screening techniques utilized in this study may potentially be applied to other peptide-drug screening processes against membrane receptor proteins.

Energy-Efficient Hosting Rich Content from Mobile Platforms with Relative Proximity Sensing.

In this paper, we present a tiny networked mobile platform, termed Tiny-Web-Thing (T-Wing), which allows the sharing of data-intensive content among objects in cyber physical systems. The object includes mobile platforms like a smartphone, and Internet of Things (IoT) platforms for Human-to-Human (H2H), Human-to-Machine (H2M), Machine-to-Human (M2H), and Machine-to-Machine (M2M) communications. T-Wing makes it possible to host rich web content directly on their objects, which nearby objects can access instantaneously. Using a new mechanism that allows the Wi-Fi interface of the object to be turned on purely on-demand, T-Wing achieves very high energy efficiency. We have implemented T-Wing on an embedded board, and present evaluation results from our testbed. From the evaluation result of T-Wing, we compare our system against alternative approaches to implement this functionality using only the cellular or Wi-Fi (but not both), and show that in typical usage, T-Wing consumes less than 15× the energy and is faster by an order of magnitude.

Bathing effects of east saline groundwater concentrates on allergic (atopic) dermatitis-like skin lesions induced by 2,4-dinitrochlorobenzene in hairless mice.

In the present study, it was evaluated whether east saline groundwater concentration solution (ESGWc) exerted a favorable inhibitory effect on 2,4-dinitrochlorobenzene (DNCB)-induced allergic/atopic-like dermatitis (AD). AD was induced and boosted by sensitization with DNCB via topical application on the dorsal back skins. Mice with DNCB-induced AD were bathed in 100-, 200- and 400-fold diluted ESGWc. After 6 weeks bathing, changes to body weight, clinical skin severity scores, scratching behavior, serum total immunoglobulin (Ig)E levels, submandibular lymph node and spleen weights, splenic cytokine levels, skin cytokine mRNA expressions, antioxidant defense systems and superoxide anion productions were recorded to determine the effects of bathing on the histopathology of dorsal back skin tissues. All DNCB-induced mice demonstrated that the induction of AD through IgE-mediated hypersensitivities, oxidative stresses, activation of MMP and apoptosis of keratinocytes resulted in no significant differences in body weight between the different groups at each time point following initial sensitization. However, markers of DNCB-induced AD were significantly inhibited (P<0.05) in a concentration-dependent manner following bathing in all concentrations of ESGWc. The results obtained in the present study suggest that bathing in ESGWc may have favorable protective effects against DNCB-induced AD due to favorable systemic and local immunomodulatory effects, active cytoprotective anti-apoptotic effects, inhibitory effects of matrix metalloproteinase activity, and anti-inflammatory and antioxidative effects.

Discovery of a potent dual ALK and EGFR T790M inhibitor.

The mutational activations of anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR) are validated oncogenic events and the targets of approved drugs to treat non-small cell lung cancer (NSCLC). Here we report highly potent dual small molecule inhibitors of both ALK and EGFR, particularly the T790M mutant which confers resistance to first generation EGFR inhibitors. Dual ALK/EGFR inhibitors may provide an efficient approach to prevent resistance that arises as a consequence of clinically reported reciprocal activation mechanisms. Our lead compound 7c displayed remarkable inhibitory activities against both ALK and EGFR in enzymatic and cellular assays. We demonstrate that 7c is capable of recapitulating the signaling effects and antiproliferative activity of combined treatment with the approved ALK inhibitor ceritinib and T790M EGFR inhibitor osimertinib against patient-derived non-small cell lung cancer cell line, DFCI032 which harbors both EML4-ALK and activated EGFR.

Genetic and Structural Characterization of a Thermo-Tolerant, Cold-Active, and Acidic Endo-ß-1,4-glucanase from Antarctic Springtail, Cryptopygus antarcticus.

The CaCel gene from Antarctic springtail Cryptopygus antarcticus codes for a cellulase belonging to the glycosyl hydrolase family 45 (GHF45). Phylogenetic, biochemical, and structural analyses revealed that the CaCel gene product (CaCel) is closely related to fungal GHF45 endo-ß-1,4-glucanases. The organization of five introns within the open reading frame of the CaCel gene indicates its endogenous origin in the genome of the species, which suggests the horizontal transfer of the gene from fungi to the springtail. CaCel exhibited optimal activity at pH 3.5, retained 80% of its activity at 0-10 °C, and maintained a half-life of 4 h at 70 °C. Based on the structural comparison between CaCel and a fungal homologue, we deduced the structural basis for the unusual characteristics of CaCel. Under acidic conditions at 50 °C, CaCel was effective to digest the green algae (Ulva pertusa), suggesting that it could be exploited for biofuel production from seaweeds.

Inter-molecular crosslinking activity is engendered by the dimeric form of transglutaminase 2.

Transglutaminase 2 (TGase 2) catalyzes a crosslink between protein bound-glutamine and -lysine. We proposed the mechanism of TGase 2 activation depends on conformation change from unfolded monomer to unfolded dimer. We found that TGase 2 has temperature-sensitive conformation change system at 30 °C. Small-angle X-ray scattering analysis showed that the enzyme was maintained as an unfolded monomer at temperatures below 30 °C, but changed to an unfolded dimer at over 30 °C. Mass analysis revealed that the C-terminus of TGase 2 was the critical region for dimerization. Furthermore, this conformational switch creates new biochemical reactivity that catalyzed inter-molecular crosslink at above 30 °C as an unfolded dimer of TGase 2 while catalyzed intra-molecular crosslink at below 30 °C as an unfolded monomer of TGase 2. The mechanism of TGase 2 activation depends on temperature-sensitive conformation change from unfolded monomer to unfolded dimer at over 30 °C. Furthermore, inter-molecular crosslinking activity is generated by the dimeric form of TGase 2. TGase 2 switches its conformation from a monomer to a dimer following a change in temperature, which engendered unique catalytic function of enzyme as inter-molecular crosslinking activity with calcium.

Leukemic infiltration presenting as myocardial hypertrophy after complete remission of acute myeloid leukemia.

Here, we report a rare case of isolated leukemic infiltrate of the myocardium (extramedullary involvement) presenting as restrictive cardiomyopathy in a patient in complete remission of acute myeloid leukemia. It was evaluated with multimodality imaging studies (echocardiography and cardiac MRI) and further confirmed by pathology. The present case highlights the importance of maintaining a high degree of clinical suspicion when evaluating patients with progressive ventricular hypertrophy of unknown cause, including recognition of the potential involvement by recurrent hematologic malignancy.