CCR8 as a Therapeutic Novel Target: Omics-Integrated Comprehensive Analysis for Systematically Prioritizing Indications.

Target identification is a crucial process in drug development, aiming to identify key proteins, genes, and signal pathways involved in disease progression and their relevance in potential therapeutic interventions. While C-C chemokine receptor 8 (CCR8) has been investigated as a candidate anti-cancer target, comprehensive multi-omics analyzes across various indications are limited. In this study, we conducted an extensive bioinformatics analysis integrating genomics, proteomics, and transcriptomics data to establish CCR8 as a promising anti-cancer drug target. Our approach encompassed data collection from diverse knowledge resources, gene function analysis, differential gene expression profiling, immune cell infiltration assessment, and strategic prioritization of target indications. Our findings revealed strong correlations between CCR8 and specific cancers, notably Breast Invasive Carcinoma (BRCA), Colon Adenocarcinoma (COAD), Head and Neck Squamous Cell Carcinoma (HNSC), Rectum adenocarcinoma (READ), Stomach adenocarcinoma (STAD), and Thyroid carcinoma (THCA). This research advances our understanding of CCR8 as a potential target for anti-cancer drug development, bridging the gap between molecular insights and creating opportunities for personalized treatment of solid tumors.

Chromosome-level genome assembly of Korean native cattle and pangenome graph of 14 Bos taurus assemblies.

This study presents the first chromosome-level genome assembly of Hanwoo, an indigenous Korean breed of Bos taurus taurus. This is the first genome assembly of Asian taurus breed. Also, we constructed a pangenome graph of 14 B. taurus genome assemblies. The contig N50 was over 55 Mb, the scaffold N50 was over 89 Mb and a genome completeness of 95.8%, as estimated by BUSCO using the mammalian set, indicated a high-quality assembly. 48.7% of the genome comprised various repetitive elements, including DNAs, tandem repeats, long interspersed nuclear elements, and simple repeats. A total of 27,314 protein-coding genes were identified, including 25,302 proteins with inferred gene names and 2,012 unknown proteins. The pangenome graph of 14 B. taurus autosomes revealed 528.47 Mb non-reference regions in total and 61.87 Mb Hanwoo-specific regions. Our Hanwoo assembly and pangenome graph provide valuable resources for studying B. taurus populations.

The QPLEX™ Plus Assay Kit for the Early Clinical Diagnosis of Alzheimer's Disease.

We recently developed a multiplex diagnostic kit, QPLEX™ Alz plus assay kit, which captures amyloid-ß1-40, galectin-3 binding protein, angiotensin-converting enzyme, and periostin simultaneously using microliters of peripheral blood and utilizes an optimized algorithm for screening Alzheimer's disease (AD) by correlating with cerebral amyloid deposition. Owing to the demand for early AD detection, we investigate the potential of our kit for the early clinical diagnosis of AD. A total of 1395 participants were recruited, and their blood samples were analyzed with the QPLEX™ kit. The average of QPLEX™ algorithm values in each group increased gradually in the order of the clinical progression continuum of AD: cognitively normal (0.382 ± 0.150), subjective cognitive decline (0.452 ± 0.130), mild cognitive impairment (0.484 ± 0.129), and AD (0.513 ± 0.136). The algorithm values between each group showed statistically significant differences among groups divided by Mini-Mental State Examination and Clinical Dementia Rating. The QPLEX™ algorithm values could be used to distinguish the clinical continuum of AD or cognitive function. Because blood-based diagnosis is more accessible, convenient, and cost- and time-effective than cerebral spinal fluid or positron emission tomography imaging-based diagnosis, the QPLEX™ kit can potentially be used for health checkups and the early clinical diagnosis of AD.

Population differentiated copy number variation between Eurasian wild boar and domesticated pig populations.

Sus scrofa is a globally distributed livestock species that still maintains two different ways of life: wild and domesticated. Herein, we detected copy number variation (CNV) of 328 animals using short read alignment on Sscrofa11.1. We compared CNV among five groups of porcine populations: Asian domesticated (AD), European domesticated (ED), Asian wild (AW), European wild (EW), and Near Eastern wild (NEW). In total, 21,673 genes were identified on 154,872 copy number variation region (CNVR). Differences in gene copy numbers between populations were measured by considering the variance-based value [Formula: see text] and the one-way ANOVA test followed by Scheffe test. As a result, 111 genes were suggested as copy number variable genes. Abnormally gained copy number on EEA1 in all populations was suggested the presence of minor CNV in the reference genome assembly, Sscrofa11.1. Copy number variable genes were related to meat quality, immune response, and reproduction traits. Hierarchical clustering of all individuals and mean pairwise [Formula: see text] in breed level were visualized genetic relationship of 328 individuals and 56 populations separately. Our findings have shown how the complex history of pig evolution appears in genome-wide CNV of various populations with different regions and lifestyles.

Novel conformation of hyaluronic acid with improved cosmetic efficacy.

BACKGROUND: Hyaluronic acid presents a valuable cosmetic ingredient that occurs naturally. Its direct links to skin aging has led to its broad application. The aim of this study was to improve the cosmetic efficacy of high molecular weight hyaluronic acid (HMWHA) without chemical modifications and evaluate such improvements through clinical and in vitro studies. METHODS: A novel formulation of HMWHA (SCAI-HA) was prepared and investigated to comparatively assess 6 clinical and 2 in vitro parameters concerning its dermatological cosmetic efficacy and biological properties. The dermatological and cellular parameters examined in this study include skin hydration, transepidermal water loss (TEWL), skin elasticity, wrinkles, facial sagging, dermal density, cytotoxicity, and collagen synthesis. RESULTS: SCAI-HA exhibited the ability to improve the tested dermatological parameters (hydration, elasticity, wrinkles, and density) to magnitudes comparable to those of HMWHA. In addition, SCAI-HA showed notably improved capacities for attenuating facial sagging and TEWL and promoting cellular collagen synthesis in normal human dermal fibroblasts. CONCLUSION: SCAI-HA presents a novel conformation of HMWHA with improved cosmetic efficacy in mitigating (i) facial sagging, (ii) TEWL, and promoting, and (iii) collagen synthesis. These findings denote the enhancement of SCAI-HA as a cosmetic ingredient with potential anti-aging properties.

Accurate Diagnosis of COVID-19 from Self-Collectable Biospecimens Using Synthetic Apolipoprotein H Peptide-Coated Nanoparticle Assay.

A high-throughput, accurate screening is crucial for the prevention and control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current methods, which involve sampling from the nasopharyngeal (NP) area by medical staffs, constitute a fundamental bottleneck in expanding the testing capacity. To meet the scales required for population-level surveillance, self-collectable specimens can be used; however, its low viral load has hindered its clinical adoption. Here, we describe a magnetic nanoparticle functionalized with synthetic apolipoprotein H (ApoH) peptides to capture, concentrate, and purify viruses. The ApoH assay demonstrates a viral enrichment efficiency of >90% for both SARS-CoV-2 and its variants, leading to an order of magnitude improvement in analytical sensitivity. For validation, we apply the assay to a total of 84 clinical specimens including nasal, oral, and mouth gargles obtained from COVID-19 patients. As a result, a 100% positivity rate is achieved from the patient-collected nasal and gargle samples, which exceeds that of the traditional NP swab method. The simple 12 min pre-enrichment assay enabling the use of self-collectable samples will be a practical solution to overcome the overwhelming diagnostic capacity. Furthermore, the methodology can easily be built on various clinical protocols, allowing its broad applicability to various disease diagnoses.

One-step assembly of barcoded planar microparticles for efficient readout of multiplexed immunoassay.

Barcoded planar microparticles are suitable for developing cost-efficient multiplexed assays, but the robustness and efficiency of the readout process still needs improvement. Here, we designed a one-step microparticle assembling chip that produces efficient and accurate multiplex immunoassay readout results. Our design was also compatible with injection molding for mass production.

Population differentiated copy number variation of Bos taurus, Bos indicus and their African hybrids.

BACKGROUND: CNV comprises a large proportion in cattle genome and is associated with various traits. However, there were few population-scale comparison studies on cattle CNV. RESULTS: Here, autosome-wide CNVs were called by read depth of NGS alignment result and copy number variation regions (CNVRs) defined from 102 Eurasian taurine (EAT) of 14 breeds, 28 Asian indicine (ASI) of 6 breeds, 22 African taurine (AFT) of 2 breeds, and 184 African humped cattle (AFH) of 17 breeds. The copy number of every CNVRs were compared between populations and CNVRs with population differentiated copy numbers were sorted out using the pairwise statistics VST and Kruskal-Wallis test. Three hundred sixty-two of CNVRs were significantly differentiated in both statistics and 313 genes were located on the population differentiated CNVRs. CONCLUSION: For some of these genes, the averages of copy numbers were also different between populations and these may be candidate genes under selection. These include olfactory receptors, pathogen-resistance, parasite-resistance, heat tolerance and productivity related genes. Furthermore, breed- and individual-level comparison was performed using the presence or copy number of the autosomal CNVRs. Our findings were based on identification of CNVs from short Illumina reads of 336 individuals and 39 breeds, which to our knowledge is the largest dataset for this type of analysis and revealed important CNVs that may play a role in cattle adaption to various environments.

The mosaic genome of indigenous African cattle as a unique genetic resource for African pastoralism.

Cattle pastoralism plays a central role in human livelihood in Africa. However, the genetic history of its success remains unknown. Here, through whole-genome sequence analysis of 172 indigenous African cattle from 16 breeds representative of the main cattle groups, we identify a major taurine × indicine cattle admixture event dated to circa 750-1,050 yr ago, which has shaped the genome of today's cattle in the Horn of Africa. We identify 16 loci linked to African environmental adaptations across crossbred animals showing an excess of taurine or indicine ancestry. These include immune-, heat-tolerance- and reproduction-related genes. Moreover, we identify one highly divergent locus in African taurine cattle, which is putatively linked to trypanotolerance and present in crossbred cattle living in trypanosomosis-infested areas. Our findings indicate that a combination of past taurine and recent indicine admixture-derived genetic resources is at the root of the present success of African pastoralism.

Recombinant adenovirus carrying a core neutralizing epitope of porcine epidemic diarrhea virus and heat-labile enterotoxin B of Escherichia coli as a mucosal vaccine.

Porcine epidemic diarrhea virus (PEDV) targets the intestinal mucosa in pigs. To protect against PEDV invasion, a mucosal vaccine is utilized effectively. In this study, we generated a recombinant adenovirus vaccine encoding the heat-labile enterotoxin B (LTB) and the core neutralizing epitope (COE) of PEDV (rAd-LTB-COE). The fusion protein LTB-COE was successfully expressed by the recombinant adenovirus in HEK293 cells, and the immunogenicity of the vaccine candidate was assessed in BALB/c mice and piglets. Three intramuscular or oral vaccinations with rAd-LTB-COE at two-week intervals induced robust humoral and mucosal immune responses. Moreover, a cell-mediated immune response was promoted in immunized mice, and the neutralizing antibody inhibited both the vaccine strain and the emerging PEDV isolate. Immunization experiments in piglets revealed that rAd-LTB-COE was immunogenic and induced good immune responses in piglets. Further studies are required to evaluate the efficacy of rAd-LTB-COE against a highly virulent PEDV challenge.

ELIPatch, a thumbnail-size patch with immunospot array for multiplexed protein detection from human skin surface.

Proteins secreted by skin have great potential as biomarkers for interpreting skin conditions. However, inconvenience in handling and bulky size of existing methods are existing limitations. Here, we describe a thumb-nail sized patch with the array of microdisks which captures multiple proteins from the skin surface. Microdisks with antibody on the surface enable multiplexed immunoassay. By self-assembly, microdisks are placed into 2-dimensional arrays on adhesive tape. The proposed Enzyme-Linked Immunospot array on a Patch shows sufficient sensitivity for IL-1α, IL1RA, IL-17A, IFN-g, and TNF-α, while IL-6 and IL-1ß are non-detectable in some cases. As demonstrations, we quantified cytokines from different skin regions and volunteers in a high-spatial-resolution.

Microbial community and functions associated with digestion of algal polysaccharides in the visceral tract of Haliotis discus hannai: Insights from metagenome and metatranscriptome analysis.

Haliotis discus hannai, a species of Pacific abalone, is a highly valuable food source throughout Northeast Asia. As H. discus hannai primarily feed on brown algae and largely extract their energy from algal polysaccharides, understanding the mechanisms by which they digest algal polysaccharides is essential for elucidating their energy metabolism. Gut microbes, as well as the host animal, are involved in the process of polysaccharide degradation. To identify algal polysaccharide-digestion mechanisms and their origin, we analyzed the metagenome and metatranscriptome of abalone visceral extracts. Microbial communities were characterized using the 16S rRNA gene sequences in the metagenome and our results differed significantly from those of previous studies using traditional microbiological methods such as bacterial cultivation and cloning. A greater diversity of bacterial taxa was identified here than was previously identified using cultivation methods. Furthermore, the most abundant bacterial taxa also differed from previous studies, which is not common when comparing the results of bacterial culturing with those of molecular methodologies. Based on the metatranscriptome, overall functions were identified and additional analyses were performed on the coding sequences of algal polysaccharide-digestive enzymes, including alginate lyase. Results of the transcriptomic analyses suggest that alginate lyase in the visceral extracts of H. discus hannai was produced by the host itself, not by visceral bacteria. This is the first next-generation sequencing study performed on abalone to characterize the visceral microbiota and the source of the ability to digest algal polysaccharides by analyzing the metagenome and metatranscriptome together.

Time-calibrated phylogenomics of the porcine epidemic diarrhea virus: genome-wide insights into the spatio-temporal dynamics.

Porcine epidemic diarrhea virus (PEDV), the causative agent of porcine epidemic diarrhea (PED), has led to tremendous economic losses in the global swine industry. Although the phylogeny of PEDV has been investigated extensively at the molecular level, there was no time-calibrated phylogenomic study on the virus. To improve insight into this topic, we analyzed 138 published genome sequences using the Bayesian coalescent analyses as well as Bayesian inferences and maximum likelihood methods. All of the global PEDV isolates were divided into six groups, except for one unclassified isolate. Of the six groups, Groups 1-5 comprised pandemic viruses while the remaining Group 6 contained classical isolates. Interestingly, the two clades, both pandemic and classical, consisted of clade-specific amino acid sequences in five genes: ORF1a, ORF1b, S, ORF3, and N. Within the pandemic clade, Group 1 and Group 2 originated from North America, whereas Group 3-Group 5 were derived from Asia. In Group 2, there was a common origin of S INDEL isolates. Within each group, there was no apparent association between temporal or geographic origin and heterogeneity of PEDVs. Our findings also showed that the PEDV virus evolved at a rate of 3.38 × 10-4 substitutions/site/year, and the most recent common ancestor of the virus emerged 75.9 years ago. Our Bayesian skyline plot analysis indicated that the PEDV had maintained constant effective population size excluding only a short period, around 2012, when a valley shaped decline in the effective number of infections occurred.

Towards encoded particles for highly multiplexed colorimetric point of care autoantibody detection.

Highly multiplexed point of care tests could improve diagnostic accuracy and differential diagnostic capacity in for instance emergency medicine and low resource environments. Available technology platforms for POC biomarker detection are typically simplex or low-plexed, whereas common lab-based microarray systems allow for the simultaneous detection of thousands of DNA or protein biomarkers. In this study, we demonstrate a novel suspension particle array platform that utilizes 900 µm bricks for POC amenable colorimetric biomarker detection with an encoding capacity of over two million. Due to the mm-scale size, both the lithographic codes and colorimetric signals of individual particles can be visualized using a consumer grade office flatbed scanner, with a potential for simultaneous imaging of around 19 000 particles per scan. The analytical sensitivity of the assay was determined to be 4 ng ml-1 using an antibody model system. As a proof of concept, autoantibodies toward anoctamin 2 were detected in order to discriminate between multiple sclerosis plasma samples and healthy controls with p < 0.0001 and an inter-assay % CV of 9.44%.

Shape-encoded silica microparticles for multiplexed bioassays.

Shape-encoded silica microparticles for use in multiplexed bioassays were fabricated by using optofluidic maskless lithography (OFML) and tetraethylorthosilicate (TEOS) polymerization. These encoded silica microparticles exhibit excellent bioconjugation properties and negligible non-specific analyte adsorption. Encoded silica microparticles could be useful in a wide variety of applications, including DNA- and protein-based diagnostics.