Early Stages Of Development Research Articles

Entrepreneurial alertness, international performance, and the role of effectuation in SME internationalization

ABSTRACT By shedding light on the often-overlooked early stages of opportunity development initiated by entrepreneurial alertness and its performance outcomes in an international setting, this study examines the interplay between alertness and two decision-making logics, effectual flexibility and causal prediction, in the context of small- and medium-sized enterprises (SMEs) internationalization. Leveraging structural equation modeling on a data set of 680 manufacturing SMEs across five countries, this study uncovers distinct effects: effectual flexibility moderates, while causal prediction mediates, the positive relationship between alertness and the international performance of SMEs. The research makes noteworthy contributions to international entrepreneurship literature by linking alertness with performance in the international context and disentangling the nuanced pathways through which SMEs can achieve success in the global arena.

The Interplay between von Hippel-Lindau Tumor Suppressor Gene, Lon Protease, ROS Accumulation, and Inflammation in Clear Cell Renal Cell Carcinoma.

This study explores the role of the von Hippel-Lindau (VHL) tumor suppressor gene and Lon protease in the development of clear cell renal carcinoma (ccRCC) through mechanisms involving inflammation and reactive oxygen species (ROS) accumulation in kidney cells. By examining the impact of VHL on the early stages of kidney cancer development, this research highlights the contributions of inflammation and ROS, as well as the involvement of Lon protease. The findings reveal increased Lon expression and ROS levels in VHL-knockdown HK-2 cells, along with elevated phospho-c-Jun N-terminal kinase (JNK) levels, emphasizing the complex interplay between VHL, Lon protease, inflammation, and ROS in kidney cell models. These insights point to potential therapeutic pathways for ccRCC.

Development and expert inspections of the user interface for a primary care decision support system

BackgroundGeneral practitioners play a unique key role in diagnosing patients with unclear diseases. Decision support systems in primary care can assist with diagnosis provided that they are efficient and user-friendly. ObjectivesThe objective of this study is to develop a high-fidelity prototype of the user interface of a clinical decision support system for primary care, particularly for diagnosis support in unclear diseases, using expert inspections at an early stage of development to ensure a high level of usability. MethodsThe user interface prototype was iteratively developed based on previous research, design principles, and usability guidelines. During the development phase, three usability inspections were carried out by all experts at four-week intervals as heuristic walkthrough. Each inspection consisted of two parts: 1) Task-based inspection 2) Free exploration and evaluation based on usability heuristics. Five domain experts assessed the current status of development.The tasks in the inspections were based on the task model derived in the requirements analysis: perform data entry, review and discuss results, schedule further diagnostics, refer to specialists and close case. ResultsAs a result of this iterative development, a high-fidelity, clickable user interface prototype was created that is able to fulfil all six tasks of our task model. The usability inspections identified a total of 196 usability issues (for all 3 inspections; Part 1: 90 issues, Part 2: 106 issues), ranging in severity from minor to severe. These served the continuous adjustment and improvement of the prototype. All main tasks were completed successfully despite these problems. ConclusionUsability inspections through heuristic walkthroughs can support and optimise the development of a user-centred decision support system in order to ensure its suitability for performing relevant tasks.

Impact of heterogenous capabilities on export performance amid the digital transformation

We investigate the effects of adopting digital technology on export performance of Korean manufacturing firms amidst the digital transformation. We recognize firm-level capabilities should be closely associated with adoption of rapidly progressing digital technology but also with export performance. And our data indicates that the most common purpose of digital technology adoption is to launch new products to the market. Hence, we consider that technology adoption is a strategic and purposeful decision to gain competitive edge mostly by producing new product, and treating technology adoption exogenous can be misleading. Due to the endogeneity and selection issues in technology adoption, the endogenous switching regression is applied to this study as Coad et al. (2020). On technology adoption decision, we find external innovative resources from strategic alliance in addition to internal innovative capabilities stand out. Given technology adoption decision, internal capabilities like patent rights and international affiliation are complementary factors to export growth. The treatment effect analysis has implications as follows: the result on contribution of technology adoption to export growth for actually adopting firms is rather small, and shows heterogenous innovation, organizational, and external capabilities are still critical factors as much as new products embedding high-end digital technology; the result on non-adopting firms indicates potential of advanced digital technology to improve export performance by helping to produce such new products if they were actually capable to do it. In sum, our findings provide another evidence that structurally positive interaction between innovative activities and export performance as Aw et al. (2011), since adoption of digital technology to products itself is innovative in the digital transformation. Furthermore, the result is consistent with the capability theory in that heterogenous innovative and complementary capabilities determine strategic technology adoption and export performance simultaneously. Finally, our findings indicate that the digital transformation might be still at the early stage. The fact that Korean firms have adopted advanced digital technology mainly for new products can be interpreted as an indicator of early development stage of transformation, since firms concentrate on product innovation than process innovation to gain competitive edge at the early stage (Utterback and Abernathy, 1975). Thus, we expect that further evolution of digital transformation can facilitate process innovation, then contribute to firm performance by improving cost efficiency that should be tackled in the upcoming study.

Relative Tumour Volume in Canine Oral Melanoma Staging and Prognosis.

Melanoma is one of the most common canine oral malignant tumours and is highly aggressive and metastatic, even at the early stages of development. Surgery relies on wide excision of the primary tumour and regional lymphadenectomy, with or without adjuvant therapy. Tumour location and size are important when considering staging, which ultimately affects the curative intent of surgery. Nevertheless, absolute tumour volume (TV) is not related to the vast phenotypic variability within canine breeds. This study aimed to determine the cutoff values of two ratios-tumour-to-head volume (THR) and tumour-to-body volume (TBR)-and assess whether they could be associated with the odds of finding metastasis at presentation and/or the likelihood of achieving tumour-free excision margins. A retrospective case series involving 51 dogs was used to evaluate the preoperative head/neck and chest computed tomography and histopathology of the primary mass and excised lymph nodes. Higher TV, THR% and TBR% values were associated with bone lysis and mitotic count (MC). The Ki67 index was significantly associated with local and distant metastases at presentation, whereas MC was associated with local metastasis alone. Tumour-infiltrated surgical margins were associated with caudally located tumours, regardless of the tumour size. Dogs with lymph node metastasis at presentation were seven times more prone to have local relapse. TV, THR% and TBR% values were positively associated with local lymph node metastasis at presentation. Cutoff values for both TV and TBR% were proposed to predict lymph node metastasis at presentation (TV = 6.423 cm3 and TBR% = 0.043), being supported by post-surgical survival analysis.

RESULTS OF ARCHAEOLOGICAL FIELDWORK IN THE DISTRICTS OF DAK SONG AND DAK MIL, DAK NONG PROVINCE, IN 2018

This study investigates the archaeological potential of Dak Nong Province, Vietnam, as revealed by fieldwork in the Dak Song and Dak Mil districts. We conducted field surveys at various sites, resulting in the discovery of a rich prehistoric heritage in the region, despite challenges posed by complex natural conditions. While artifact distribution and concentration vary across sites, we identified significant concentrations in areas near lakes, rivers, and streams. We find that at locations such as Village 9A, volcanic Lake Dak Mil, and Tay Son Village, traces of concentration are faint. In contrast, at sites such as Dak Peur Border Gate and Tan Lap Village, there are traces of a dense population and long occupation by prehistoric people. The prehistoric inhabitants of Dak Mil and Dak Song districts often lived along lakes, rivers, and streams that did not dry up in the dry season; they lived in a large area and were highly mobile. Our preliminary research highlights the value of Dak Nong Province in studying the early stages of prehistory and cultural development in the Central Highlands region of Vietnam. This also underscores the importance of preserving and promoting archaeological heritage in Dak Mil and Dak Song districts.

Quantitative prediction of drug-drug interactions caused by CYP3A induction using endogenous biomarker 4β-hydroxycholesterol.

Evaluation of the CYP3A induction risk is important in early drug development stages. This study focused on 4β-hydroxycholesterol (4β-HC) as an endogenous biomarker of drug-drug interactions (DDIs) caused by CYP3A induction. We investigated a new approach using 4β-HC for quantitative prediction of DDIs caused by CYP3A induction based on the mechanistic static pharmacokinetic (MSPK) model. The induction ratio, i.e., the ratio of plasma 4β-HC or 4β-HC/cholesterol (4β-HC/C) with and without a co-administered CYP3A inducer, and the ratio of the area under the plasma concentration-time curve (AUCR), i.e., the ratio of the AUC of plasma CYP3A substrate drugs with and without a co-administered CYP3A inducer, were collected. The scaling factor d in the MSPK model was calculated from the induction ratio of 4β-HC or 4β-HC/C based on the systemic term in the MSPK model. The AUCR of 18 CYP3A substrates with and without co-administration of 7 CYP3A inducers were then predicted by substituting the calculated d value into the MSPK model. This approach showed that approximately 84% of the predicted AUCR values were within a two-fold range of the observed values, showing that this approach can be a good tool to quantitatively predict DDIs caused by CYP3A induction. Significance Statement A concise approach to predict drug interactions with adequate accuracy is preferable in the early drug development stage. In this study, a new approach using 4β-hydroxycholesterol for quantitative prediction of DDIs caused by CYP3A induction was investigated. The predictability was verified using 7 CYP3A inducers and 18 substrates.

Innovations in cancer diagnosis and treatment: prospects and challenges

The research relevance of cancer diagnostics and treatment is determined by its widespread occurrence and the lack of adequate modern diagnostic methods. The study aims to characterise new diagnostic methods, namely screenings in detecting cancer at early stages of development. To achieve this goal, the bibliosemantic and bibliographic methods were used. Main results. Cancer is the leading cause of morbidity and mortality after cardiovascular diseases and injuries in many countries around the world. Various diagnostic and treatment methods are used to combat this problem, including computed tomography, magnetic resonance imaging and positron emission tomography. In addition, modern diagnostic methods such as polymerase chain reaction, mass spectrometry and genomic sequencing play an important role in determining the types of cancer cells and their sensitivity to treatment. These advanced methods can be used to diagnose cancer more accurately and efficiently and choose the most appropriate treatment strategies for each patient. The practical significance of this topic is to ensure appropriate care for patients with cancer: providing high-quality, efficient, fast and minimally invasive diagnostics using the latest methods, as well as implementing a screening system.

WaSPred: A reliable AI-based water solubility predictor for small molecules

A rapid and reliable evaluation of the aqueous solubility of small molecules is a hot topic for the scientific community and represents a field of particular interest in drug discovery. In fact, aqueous solubility significantly impacts various aspects that collectively influence a drug’s overall pharmacokinetics, including absorption, distribution and metabolism. For this reason, in silico approaches that provide fast and cost-effective solubility predictions, can serve as invaluable tools in the early stages of drug development. Although additional molecular features should be considered, accurate solubility predictions can help medicinal chemists rationally planning the synthesis of compounds more likely to exhibit desirable pharmacokinetic properties and in selecting the most promising candidates for further biological testing (e.g., cellular assays) from an initial pool of hit compounds with detected preliminary bioactivity. In this context, we herein report the development and evaluation of WaSPred, our AI-based water solubility predictor for small molecules. WaSPred not only showed high reliability in water solubility predictions performed on structurally heterogeneous compounds, belonging to multiple external datasets, but also demonstrated superior performance compared to a set of other commonly used water solubility predictors, thus confirming its state-of the-art robustness and its usefulness as an in silico approach for water solubility evaluations..

Genome-Wide Characterization and Expression Profiling of Phytosulfokine Receptor Genes (PSKRs) in Triticum aestivum with Docking Simulations of Their Interactions with Phytosulfokine (PSK): A Bioinformatics Study.

Background/Objectives: The phytosulfokine receptor (PSKR) gene family plays a crucial role in regulating plant growth, development, and stress response. Here, the PSKR gene family was characterized in Triticum aestivum L. The study aimed to bridge knowledge gaps and clarify the functional roles of TaPSKRs to create a solid foundation for examining the structure, functions, and regulatory aspects. Methods: The investigation involved genome-wide identification of PSKRs through collection and chromosomal assignment, followed by phylogenetic analysis and gene expression profiling. Additionally, interactions with their interactors were stimulated and analyzed to elucidate their function. Results: The wide-genome inspection of all TaPSKRs led to 25 genes with various homeologs, resulting in 57 TaPSKR members distributed among the A, B, and D subgenomes. Investigating the expression of 61 TaPSKR cDNAs in RNA-seq datasets generated from different growth stages at 14, 21, and 60 days old and diverse tissues such as leaves, shoots, and roots provided further insight into their functional purposes. The expression profile of the TaPSKRs resulted in three key clusters. Gene cluster 1 (GC 1) is partially associated with root growth, suggesting that specific TaPSKRs control root development. The GC 2 cluster targeted genes that show high levels of expression in all tested leaf growth stages and the early developmental stage of the shoots and roots. Furthermore, the GC 3 cluster was composed of genes that are constantly expressed, highlighting their crucial role in regulating various processes during the entire life cycle of wheat. Molecular docking simulations showed that phytosulfokine type α (PSK-α) interacted with all TaPSKRs and had a strong binding affinity with certain TaPSKR proteins, encompassing TaPSKR1A, TaPSKR3B, and TaPSKR13A, that support their involvement in PSK signaling pathways. The crucial arbitration of the affinity may depend on interactions between wheat PSK-α and PSKRs, especially in the LRR domain region. Conclusions: These discoveries deepened our knowledge of the role of the TaPSKR gene family in wheat growth and development, opening up possibilities for further studies to enhance wheat durability and yield via focused innovation approaches.

Digital assessments for children and adolescents with ADHD: a scoping review.

In spite of rapid advances in evidence-based treatments for attention deficit hyperactivity disorder (ADHD), community access to rigorous gold-standard diagnostic assessments has lagged far behind due to barriers such as the costs and limited availability of comprehensive diagnostic evaluations. Digital assessment of attention and behavior has the potential to lead to scalable approaches that could be used to screen large numbers of children and/or increase access to high-quality, scalable diagnostic evaluations, especially if designed using user-centered participatory and ability-based frameworks. Current research on assessment has begun to take a user-centered approach by actively involving participants to ensure the development of assessments that meet the needs of users (e.g., clinicians, teachers, patients). The objective of this mapping review was to identify and categorize digital mental health assessments designed to aid in the initial diagnosis of ADHD as well as ongoing monitoring of symptoms following diagnosis. Results suggested that the assessment tools currently described in the literature target both cognition and motor behaviors. These assessments were conducted using a variety of technological platforms, including telemedicine, wearables/sensors, the web, virtual reality, serious games, robots, and computer applications/software. Although it is evident that there is growing interest in the design of digital assessment tools, research involving tools with the potential for widespread deployment is still in the early stages of development. As these and other tools are developed and evaluated, it is critical that researchers engage patients and key stakeholders early in the design process.

Modeling the pre-symptomatic stage of hemi-parkinsonian state in animals (rodents and monkeys)

The behavioral and functional states preceding the onset specific parkinsonian symptoms were studied at an early (pre-symptomatic) stage of hemi-parkinsonian syndrome development in rodents and monkeys. The pre-symptomatic stage of the hemi-parkinsonian syndrome was determined in rodents (mice and rats) treated by chronic administration of low doses of rotenone toxin. The consecutive steps of neuropathological traits development in rodents included the cognitive impairment at the 1st-2nd week of exposure to rotenone, minor movement disorders at the 3st-4nd week before the onset of severe motor dysfunction as well as some biochemical indicators. The latencies and amplitudes of visually guided saccades (VGS) while conditioned instrumental task performing were studied in nonhuman primates (Macaca mulatta) chronically treated with low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The elongation of VGS latencies and the decline of their accuracy were revealed with development of MPTP-induces syndrome but conditioned instrumental performance was not affected. The negative behavioral effects manifested in animals at the pre-symptomatic stage of toxins induced disease both in the rotenone model in rodents and in MPTP model in monkeys suggesting them as early markers of a hemi-parkinsonian syndrome.

Generation of human-pig chimeric renal organoids using iPSC technology

Porcine organs and human induced pluripotent stem cell (iPSC)-derived organoids as alternative organs for human transplantation have garnered attention, but both face technical challenges. Interspecies chimeric organ production using human iPSCs shows promise in overcoming these challenges. Our group successfully generated chimeric renal organoids using human iPSC-derived nephron progenitor cells (NPCs) and fetal mouse kidneys. However, the current technology is limited to rodents. Therefore, this study focused on producing human-pig chimeric renal organoids, as pigs are the most promising species for xenotransplantation. Modification of existing culture systems enables continuous renal development in both species, resulting in the successful creation of human-pig chimeric renal organoids. Moreover, this method can be applied to generate humanized xenogeneic kidneys for future clinical applications. This study provides evidence that optimizing culture conditions enables the early-stage kidney development beyond species barriers, thus laying the foundation for accelerating research on humanized xenogeneic kidney fabrication for clinical purposes.

Bacteria as potential biocontrol agents for managing purple witchweed (Striga hermonthica) in grain sorghum

Abstract Purple witchweed [Striga hermonthica (Delile) Benth.], a highly destructive parasitic weed, poses a significant threat to sorghum [Sorghum bicolor (L.) Moench] cultivation. This hemiparasitic plant intrudes its root system into the host plant, leading to substantial yield losses, particularly in susceptible genotypes. In the pursuit of eco-friendly solutions, the biocontrol approach has gained attention as a potential management strategy for Striga. In this study, 13 bacterial strains belonging to the genera Bacillus, Gluconobacter, Pseudomonas, and Streptomyces were investigated in vitro for their efficiency in controlling the early-stage development of Striga. Among the tested strains, Streptomyces morookaensis NRRL B-12429 demonstrated significant inhibition of Striga seed germination and radicle elongation at 54.36% and 61.84%, respectively, when applied to preconditioned seeds with a synthetic germination stimulant. The effect of S. morookaensis on the inhibition of Striga seed germination was more pronounced in the presence of the host plant, sorghum, at 62.35%. However, biopriming of sorghum seeds with S. morookaensis did not enhance the inhibitory effects on Striga seed germination but resulted in a greater reduction in radicle elongation at 74.64% compared with non-primed seeds. Additionally, the biopriming with S. morookaensis promoted the growth of shoots and roots of germinating sorghum, regardless of the presence of Striga seeds. These findings highlight the potential of S. morookaensis strain NRRL B-12429 as a viable candidate for biocontrol agent applications in sorghum cultivation. Further exploration and investigation of its biocontrol capabilities can provide valuable insights for sustainable management practices against Striga infestations.

A PROSPECTIVE OBSERVATIONAL STUDY OF MONITORING AND REPORTING OF ANTIMICROBIAL DRUGS ASSOCIATED ADVERSE DRUG REACTIONS AND THEIR SIGNIFICANCE ON PATIENTS SAFETY AND HEALTH-CARE OUTCOMES

Objective: Adverse drug reaction (ADR) surveillance and reporting practices are at an early stage of development within the Indian context. The pharmacovigilance rate in India falls below 1%, which is notably lower compared to the global average of 5%. India holds the position of being the fourth most significant contributor to the pharmaceutical industry worldwide. Therefore, there exists a pressing demand to enhance the pharmacovigilance framework for safeguarding the health of the Indian population. ADR is defined as the unintended, obnoxious, and unwanted reaction due to the use of a drug. The administration of antimicrobial agents causes various ADR that has been analyzed throughout the study. The main objective of the research is to monitor and report the adverse drug reaction caused by antimicrobial drugs Methods: A prospective observational study was carried out in the various departments of the hospital with duration of 3 months including 100 patients using patient profile form and ADR reporting forms and analyzing with the scales for causality, severity, and preventability assessment. Results: During the study, 29 ADRs were found among 100 patients, with an incidence rate of 9.6%, more common in females (52%) than in males (48%). ADRs were most frequently reported in the age group of 35–51 years (34%), then 18–34 years (28%), and 1–17 years (24%). The general medicine department reported the highest number of ADRs (66%), followed by the pediatric department (24%). Cephalosporins caused the most ADRs (35%). Common ADRs included constipation, diarrhea (34%) and rashes, nausea, and vomiting (34%). Naranjo scale indicated that the causality of ADRs was probable (52%). Hartwig severity scale showed 55% ADRS to be mild. Schumock and Thornton method found that 76% of ADRs were preventable.Management of most of ADRs included drug withdrawal (52%). Conclusion: The majority of cephalosporin-related side effects, which included constipation, diarrhoea, and rashes, were observed. Most of the patients got better with the help of ADR monitoring and management. Finding and treating drug-related problems early make patients feel better and keep them safe. This study shows health-care system why it is important to monitor and report ADR caused by drugs.

Fugazi regulation for AI: strategic tolerance for ethics washing

AbstractRegulation theory offers a unique perspective on the institutional aspects of digital capitalism’s accumulation regime. However, a gap exists in examining the associated mode of regulation. Based on the analysis of AI ethics washing phenomenon, we suggest the state is delicately balancing between fueling innovation and reducing uncertainty in emerging technologies. This balance leads to a unique mode of regulation, "Fugazi regulation," characterized by vaguely defined, non-enforceable moral principles with no specific implementation mechanisms. We propose a microeconomic model that rationalizes this approach and shows that it is justifiable when the government struggles to differentiate between benign and harmful technology use due to capacity constraints. The potential for private companies to adopt ethical practices under Fugazi regulation supports the government’s preference for this method. This regulation mode is particularly attractive to the government during technology’s early development stages, marked by governmental optimism and uncertainty about the technology. Implications for greenwashing are also derived from the analysis.

Toxicity of Nitrite to Juvenile Sunray Surf Clam (Mactra chinensis Philippi)

Nitrite is a common pollutant in marine environments and can cause mortality in crustaceans and bivalves. The purpose of the current study is to understand nitrate’s toxicity to juvenile clams due to its potential impact on aquaculture and marine ecosystems. Juvenile sunray surf clams (Mactra chinensis Philippi) (1.00 ± 0.10 cm shell length, 0.75 ± 0.04 cm shell height) were exposed to varying concentrations of nitrite for 96 h and 20 days, respectively. The LC50 for survival at 96 h was 37 mg/L NO2-N. Histological evaluations were made on juvenile clams exposed at 30 mg/L after 20 d of exposure. Epithelial cells and digestive diverticulum are the best sub-lethal effect indicators. Shell length and antioxidant enzyme activities were measured at the beginning of the experiment and then observed 10 and 20 days after exposure. A logarithmic relationship was obtained between the relative growth rate (based on the shell length) of juvenile M. chinensis and the nitrite concentration. Compared to the control, activity suppression of superoxide dismutase and catalase activity was detected from the concentration of 1 mg/L NO2-N. It is recommended that nitrite concentrations remain below 1 mg/L to prevent stress during the early developmental stages of clams.

A molecular approach to identify parrotfish (Sparisoma) species during early ontogeny.

Sparisoma species (parrotfish) comprise an important functional group contributing to coral-reef resilience. The morphological diagnostic characteristics for species identification are clearly described for adult forms but not for the early stages. Consequently, many taxonomical listings of Sparisoma larvae are restricted to the genus level. The aims of this study are to determine whether the morphological and molecular identification techniques are useful to assign the species taxonomic level to Sparisoma larvae occurring in the Gulf of Mexico and whether there is a set of diagnostic features that could be used to discriminate between species in larvae of different developmental stages. Morphological assignment of Sparisoma was performed based on morphological and meristic features for 30 larvae collected in the Gulf of Mexico from late August to mid-September 2015. To corroborate and complement the morphological assignments, molecular identification was carried out using DNA sequences from regions of two mitochondrial genes, mitochondrial cytochrome oxidase I (mtDNA COI) and mitochondrial 16S rRNA (mtDNA 16S rRNA). COI and 16S gene trees for Sparisoma and related fish taxa were constructed using sequences available in the NCBI (National Center for Biotechnology Information) GenBank and BOLD (Barcode of Life Data) databases. Two morphotypes were identified based on morphology, but no diagnostic characteristics for species discrimination were found. Molecular identification, in contrast, successfully discriminated four early development stages of Sparisoma atomarium, three stages of Sparisoma radians, and two stages of Sparisoma chrysopterum and Sparisoma aurofrenatum, therefore demonstrating the successful and necessary application of molecular taxonomic approaches for species-level identifications of Sparisoma larvae.

Molecular interactions of plant-derived inhibitors from Euphorbia hirta against binding sites of HPV E6 and E7 oncoproteins - An in-silico analysis

Although no cure for Human Papilloma virus (HPV) exists at the moment, effective vaccines are present that can prevent the most harmful strains of the virus from infecting people. While potential cures like therapeutic vaccines, immunotherapy, and gene therapy are still in the early stages of development and may take years to become widely available, we focussed on using traditional Siddha-based medicines (phytochemicals of Euphorbia hirta L.) as a prospect through in-silico docking studies. Twelve phytochemicals from Euphorbia hirta L. were selected to investigate the antiviral properties against HPV. These ligand structures were obtained from PubChem database, prepared for docking with two major HPV targets i.e., E6 and E7 oncoproteins obtained from PDB, using AutoDock tools. The analysis revealed the potential of lobeline and euphol ligands effectively binding to the active sites of E6 and E7 proteins respectively. Using the ADMET lab 2.0 server, the ligands were evaluated for their commercial drug potential by considering their absorption, distribution, metabolism, excretion, and toxicity properties.

Detection and Localization of IL-8 and CXCR1 in Rainbow Trout Larvae in Response to Pseudomonas aeruginosa Lipopolysaccharide

The salmonid industry faces challenges due to the susceptibility of fish to opportunistic pathogens, particularly in early developmental stages. Understanding the immunological capacity during these stages is crucial for developing effective disease control strategies. IL-8R, a member of the G-protein-coupled receptor family, acts as a receptor for Interleukin 8 (IL-8). The binding of IL-8 to IL-8R plays a major role in the pathophysiology of a wide spectrum of inflammatory conditions. This study focused on the immune response capacity of rainbow trout (Oncorhynchus mykiss) larvae by analyzing IL-8/CXCR1 response to lipopolysaccharide (LPS) from Pseudomonas aeruginosa. Previous research demonstrated that LPS from P. aeruginosa acts as a potent immunostimulant in teleost, enhancing pro-inflammatory cytokines. The methodology included in silico analysis and the synthesis and characterization of an omCXCR1-derived epitope peptide, which was used to produce omCXCR1-specific anti98 serum in mice. The research revealed that rainbow trout larvae 19 days post-hatching (dph) exhibited pronounced immune responses post-stimulation with 1 µg/mL of LPS. This was evidenced by the upregulated protein expression of IL-8 and omCXCR1 in trout larvae 2 and 8 h after LPS challenge, as analyzed by ELISA and immunohistochemistry. Furthermore, fluorescence microscopy successfully revealed the colocalization of IL-8 and its receptor in cells from mucosal tissues after LPS challenge in larvae 19 dph. These findings underscore the efficacy of LPS immersion as a method to activate the innate immune system in trout larvae. Furthermore, we propose IL-8 and its receptor as molecular markers for evaluating immunostimulation in the early developmental stages of salmonids.