Synthesis of 2,4-dihydroxyacetophenone derivatives as potent PDE-1 and -3 inhibitors: in vitro and in silico insights.

Aim: Synthesis of novel bis-Schiff bases having potent inhibitory activity against phosphodiesterase (PDE-1 and -3) enzymes, potentially offering therapeutic implications for various conditions. Methods: Bis-Schiff bases were synthesized by refluxing 2,4-dihydroxyacetophenone with hydrazine hydrate, followed by treatment of substituted aldehydes with the resulting hydrazone to obtain the product compounds. After structural confirmation, the compounds were screened for their in vitro PDE-1 and -3 inhibitory activities. Results: The prepared compounds exhibited noteworthy inhibitory efficacy against PDE-1 and -3 enzymes by comparing with suramin standard. To clarify the binding interactions between the drugs, PDE-1 and -3 active sites, molecular docking studies were carried out. Conclusion: The potent compounds discovered in this study may be good candidates for drug development.

[Box: see text].

Enhancing Human Health and Wellbeing through Sustainably and Equitably Unlocking a Healthy Ocean's Potential.

A healthy ocean is essential for human health, and yet the links between the ocean and human health are often overlooked. By providing new medicines, technologies, energy, foods, recreation, and inspiration, the ocean has the potential to enhance human health and wellbeing. However, climate change, pollution, biodiversity loss, and inequity threaten both ocean and human health. Sustainable realisation of the ocean's health benefits will require overcoming these challenges through equitable partnerships, enforcement of laws and treaties, robust monitoring, and use of metrics that assess both the ocean's natural capital and human wellbeing. Achieving this will require an explicit focus on human rights, equity, sustainability, and social justice. In addition to highlighting the potential unique role of the healthcare sector, we offer science-based recommendations to protect both ocean health and human health, and we highlight the unique potential of the healthcare sector tolead this effort.

Study of MoS2 as an Electric Field Sensor and the Role of Layer Thickness on the Sensitivity.

In this study, we investigate the scope of molybdenum disulfide (MoS2) as an electric field sensor. We show that MoS2 sensors can be used to identify the polarity as well as to detect the magnitude of the electric field. The response of the sensor is recorded as the change in the drain current when the electric field is applied. The sensitivity, defined as the percentage change in the drain current, reveals that it has a linear relation with the magnitude of the electric field. Furthermore, the sensitivity is highly dependent on the layer thickness, with the single-layer device being highly sensitive and the sensitivity decreasing with the thickness. We have also compared the electric field sensitivity of MoS2 devices to that of previously studied graphene devices and found the former to be exceptionally sensitive than the latter for a given electric field magnitude.

Impact of ALDH1A1 and NQO1 gene polymorphisms on the response and toxicity of chemotherapy in Bangladeshi breast cancer patients.

PURPOSE: Cyclophosphamide, Epirubicin/Doxorubicin, 5-fluorouracil (CEF or CAF) chemotherapy has long been a standard first-line treatment for breast cancer. The genetic variations of enzymes that are responsible for the metabolism of these drugs have been linked to altered treatment response and toxicity. Two drug-metabolizing enzymes ALDH1A1 and NQO1 are critically involved in the pathways of CEF/CAF metabolism. This study aimed to evaluate the effect of ALDH1A1 (rs13959) and NQO1 (rs1800566) polymorphisms on treatment response and toxicities caused by adjuvant (ACT) and neoadjuvant chemotherapy (NACT) where CEF/CAF combination was used to treat Bangladeshi breast cancer patients. METHODS: A total of 330 patients were recruited from various hospitals, with 150 receiving neoadjuvant chemotherapy and 180 receiving adjuvant chemotherapy. To extract genomic DNA, a non-enzymatic simple salting out approach was adopted. The polymerase chain reaction-restriction fragment length polymorphism method was used to detect genetic polymorphisms. Unconditional logistic regression was used to derive odds ratios (ORs) with 95% confidence intervals (CIs) to study the association between genetic polymorphisms and clinical outcome and toxicity. RESULTS: A statistically significant association was observed between ALDH1A1 (rs13959) polymorphism and treatment response (TT vs. CC: aOR = 6.40, p = 0.007; recessive model: aOR = 6.38, p = 0.002; allele model: p = 0.032). Patients with the genotypes TT and CT + TT of the NQO1 (rs1800566) polymorphism had a significantly higher risk of toxicities such as anemia (aOR = 0.34, p = 0.006 and aOR = 0.58, p = 0.021), neutropenia (aOR = 0.42, p = 0.044 and aOR = 0.57, p = 0.027), leukopenia (aOR = 0.33, p = 0.010 and aOR = 0.46, p = 0.005), and gastrointestinal toxicity (aOR = 0.30, p = 0.02 and aOR = 0.38, p = 0.006) when compared to the wild CC genotype, while patients with the genotype CT had a significant association with gastrointestinal toxicity (aOR = 0.42, p = 0.02) and leukopenia (aOR = 0.52, p = 0.010). The TT and CT + TT genotypes of rs13959 had a significantly higher risk of anemia (aOR = 2.00, p = 0.037 and aOR = 1.68, p = 0.029). There was no significant association between rs1800566 polymorphism and treatment response. CONCLUSION: Polymorphisms in ALDH1A1 (rs13959) and NQO1 (rs1800566) may be useful in predicting the probability of treatment response and adverse effects from CEF or CAF-based chemotherapy in breast cancer patients.

Evolving Concepts of Pain Management in Elderly Patients.

PURPOSE OF REVIEW: The elderly population typically suffer from a variety of diseases that mostly reflect the degenerative changes linked with the aging process. These diseases may be exacerbated by acute pain or by an abrupt aggravation of previously stable chronic pain. RECENT FINDINGS: Physical and psychological changes associated with aging may influence one's experience of pain and, as a result, the severity of pain. Pain treatment in the elderly can be complex and is often a budgetary burden on the nation's health care system. These difficulties arise, in part, because of unanticipated pharmacodynamics, changed pharmacokinetics, and polypharmacy interactions. Therefore, it is critical to integrate a multidisciplinary team to develop a management strategy that incorporates medical, psychological, and surgical methods to control persistent pain conditions. It is in this critical process that pain prediction models can be of great use. The purpose of pain prediction models for the elderly is the use of mathematical models to predict the occurrence and intensity of pain and pain-related conditions. These mathematical models employ a vast quantity of data to ascertain the many risk factors for the development of pain problems in the elderly, whether said risks are adjustable or not. These models will pave the way for more informed medical decision making that are based on the findings of thousands of patients who have previously experienced the same illness and related pain conditions. However, future additional research needs to be undertaken to build prediction models that are not constrained by substantial legal or methodological limitations.

Investigating the Anticancer Effects of Pleurotus Ostreatus Polysaccharide on G0/G1 Cell Cycle Arrest and Apoptosis in Ehrlich Ascites Carcinoma Cells.

Cancer is one of the leading causes of mortality worldwide. Despite the advancement of cancer treatment by various means including surgery, chemotherapy, etc., cancer is still a challenging disease to manage. This study was undertaken to investigate extraction, purification, structural elucidation, and the potential anti-cancer effects of Pleurotus ostreatus polysaccharide (POP). The anti-cancer activities were performed on the Ehrlich Ascites Carcinoma Cell Line. The results demonstrated that the MW of  POP was154649.8 Da with homopolysaccharide composed of D-glucose units, featuring (1→6)-α-D-Glcp backbone with O-6 branches and T-α-D-Glcp terminations. and the yield was 6.27%. was 6.27%, The antitumor activity assessment demonstrated significant cytotoxicity of POP against Ehrlich Ascites Carcinoma (EAC) cells, with an IC50 of 121.801 µg/mL, supported by LDH release analysis. POP inhibited cell migration, invasion, and colony formation, indicating its potential as an anti-cancer agent. POP elicited the apoptotic activity with the upregulation of Caspase-9 and Bax, and downregulation of Bcl-2. The DNA fragmentation assay further confirmed apoptosis-mediated DNA degradations. Additionally, POP-induced cell cycle arrest at the G0/G1 phase, by altering the expression of p53, Cyclin D, and Cdk4 proteins. So, Pleurotus ostreatus polysaccharide (POP) showed significant cytotoxicity on Ehrlich Ascites Carcinoma cells, indicating potential as an anti-cancer agent.

Maternal betel quid use during pregnancy and child growth: a cohort study from rural Bangladesh.

BACKGROUND: Chewing betel quid (BQ) - a preparation commonly containing areca nut and slaked lime wrapped in betel leaf - is entrenched in South Asia. Although BQ consumption during pregnancy has been linked to adverse birth outcomes, its effect on postnatal growth remains largely unexplored. OBJECTIVE: We examined the associations of BQ use during pregnancy with children's height-for-age and body mass index-for-age z-scores (HAZ and BAZ, respectively) and fat and fat-free mass along with sex-based differences in association in rural Bangladesh. METHODS: With a prospective cohort design, we assessed BQ use among mothers enrolled in the Preterm and Stillbirth Study, Matlab (n = 3140) with a structured questionnaire around early third trimester. Children born to a subset of 614 women (including 134 daily users) were invited to follow-up between October 2021 and January 2022. HAZ and BAZ were calculated from anthropometric assessment, and fat and fat-free mass were estimated using bioelectric impedance. Overall and sex-specific multiple linear regression models were fitted. RESULTS: Growth data were available for 501 children (mean age 4.9 years): 43.3% of them were born to non-users, 35.3% to those using prior to or less-than-daily during the survey, and 21.3% to daily users. No statistically significant associations were observed after adjusting for sex, parity, maternal height and education, and household wealth. CONCLUSIONS: There was no effect of BQ use during pregnancy on postnatal growth in this study. Longitudinal studies following up those born to heavy users beyond childhood are warranted for capturing long-term implications of prenatal BQ exposure.

Main findings: In this cohort study, no association was observed between maternal betel quid use during pregnancy and children's growth around five years of age.Added knowledge: Although catch-up growth among those born to heavy users may have attenuated any negative impact of prenatal exposure to betel quid on postnatal growth, such catch-up growth often involves greater acquisition and a more centralized distribution of body fat and insulin resistance later in life; leading to a potential heightening of cardiometabolic risk.Global health impact for policy and action: Given that betel quid consumption during pregnancy remains socially acceptable across south and south-east Asia, this study highlights the need for following up those born to betel quid users beyond childhood for capturing long-term health implications of prenatal betel quid exposure.

The HyperPed-COVID international registry: Impact of age of onset, disease presentation and geographical distribution on the final outcome of MIS-C.

OBJECTIVES: The aim of the study was to establish an international multicenter registry to collect data on patients with Multisystem Inflammatory Syndrome in Children (MIS-C), in order to highlight a relationship between clinical presentation, age of onset and geographical distribution on the clinical outcome. STUDY DESIGN: Multicenter retrospective study involving different international societies for rare immunological disorders.1009 patients diagnosed with MIS-C between March and September 2022, from 48 centers and 22 countries were collected. Five age groups (<1, 1-4, 5-11, 12-16, >16 years) and four geographic macro-areas, Western Europe, Central-Eastern Europe, Latin America, Asian-African resource-limited countries (LRC), were identified. RESULTS: Time to referral was significantly higher in LRC. Intensive anti-inflammatory treatment, including biologics, respiratory support and mechanic ventilation were more frequently used in older children and in European countries. The mortality rate was higher in very young children (<1 year), in older patients (>16 years of age) and in LRC. Multivariate analysis identified the residence in LRC, presence of severe cardiac involvement, renal hypertension, lymphopenia and non-use of heparin prophylaxis, as the factors most strongly associated with unfavorable outcomes. CONCLUSIONS: The stratification of patients by age and geographic macro-area provided insights into the clinical presentation, treatment and outcome of MIS-C. The mortality and sequelae rates exhibited a correlation with the age and geographical areas. Patients admitted and treated in LRC displayed more severe outcomes, possibly due to delays in hospital admission and limited access to biologic drugs and to intensive care facilities.

Comparative analysis of essential oil efficacy against the Asian longhorned tick Haemaphysalis longicornis (Acari: Ixodidae).

This study evaluated the potential repellent and acaricidal effects of 4 essential oils (clove, eucalyptus, lavender, and mint) against the Asian longhorned tick Haemaphysalis longicornis, a vector of various tick-borne diseases in medical and veterinary contexts. Selected for their potential repellent and acaricidal properties, the 4 essential oils were tested on adult and nymph H. longicornis ticks at different concentrations. The experiment assessed mortality rates and repellency, particularly during tick attachment to host skin. There was a significant increase (p<0.05) in tick mortality and repellency scores across all groups. At a 1% concentration, adult tick mortality ranged from 36% to 86%, while nymph mortality ranged from 6% to 97%. Clove oil exhibited notable efficacy, demonstrating high mortality rates of nymphs and adults. Clove oil also displayed strong repellency properties, with a repellency index of 0.05, surpassing those of mint, eucalyptus, and lavender oils. Clove oil showed the highest effectiveness in deterring nonattached adult ticks (90%) and nymphs (95%) when applied to skin. Clove oil was the most effective against adult and nymph ticks, achieving mortality rates of 86% and 97%, respectively, and led to the highest nonattachment rates when applied to skin. In conclusion, essential oils such as clove, eucalyptus, lavender, and mint oils present promising results for tick population control.

Molecular cloning, identification, transcriptional analysis, and silencing of enolase on the life cycle of Haemaphysalis longicornis (Acari, Ixodidae) tick.

Ticks, blood-sucking ectoparasites, spread diseases to humans and animals. Haemaphysalis longicornis is a significant vector for tick-borne diseases in medical and veterinary contexts. Identifying protective antigens in H. longicornis for an anti-tick vaccine is a key tick control strategy. Enolase, a multifunctional protein, significantly converts D-2-phosphoglycerate and phosphoenolpyruvate in glycolysis and gluconeogenesis in cell cytoplasm. This study cloned a complete open reading frame (ORF) of enolase from the H. longicornis tick and characterized its transcriptional and silencing effect. We amplified the full-length cDNA of the enolase gene using rapid amplification of cDNA ends. The complete cDNA, with an ORF of 1,297 nucleotides, encoded a 432-amino acid polypeptide. Enolase of the Jeju strain H. longicornis exhibited the highest sequence similarity with H. flava (98%), followed by Dermacentor silvarum (82%). The enolase motifs identified included N-terminal and C-terminal regions, magnesium binding sites, and several phosphorylation sites. Reverse transcription-polymerase chain reaction (RT-PCR) analysis indicated that enolase mRNA transcripts were expressed across all developmental stages of ticks and organs such as salivary gland and midgut. RT-PCR showed higher transcript levels in syn-ganglia, suggesting that synganglion nerves influence enolase,s role in tick salivary glands. We injected enolase double-stranded RNA into adult unfed female ticks, after which they were subsequently fed with normal unfed males until they spontaneously dropped off. RNA interference significantly (P<0.05) reduced feeding and reproduction, along with abnormalities in eggs (no embryos) and hatching. These findings suggest enolase is a promising target for future tick control strategies.

CDK: A novel high-performance transfer feature technique for early detection of osteoarthritis.

Knee osteoarthritis (OA) is a prevalent condition causing significant disability, particularly among the elderly, necessitating advancements in diagnostic methodologies to facilitate early detection and treatment. Traditional OA diagnosis, relying on radiography and physical exams, faces limitations in accuracy and objectivity. This underscores the need for more advanced diagnostic methods, such as machine learning (ML) and deep learning (DL), to improve OA detection and classification. This research introduces a novel ensemble learning approach for image data feature extraction which ingeniously combines the strengths of 2 advanced (ML) models with a (DL) method to substantially improve the accuracy of OA detection from radiographic images. This innovative strategy aims to address the limitations of traditional diagnostic tools by leveraging the enhanced sensitivity and specificity of combined ML and DL models. The methodology deployed in this study encompasses the application of 10 ML models to a comprehensive publicly available Kaggle dataset with a total of 3615 samples of knee X-ray images. Through rigorous k-fold cross-validation and meticulous hyperparameter optimization, we also included evaluation metrics like accuracy, receiver operating characteristic, precision, recall, and F1-score to assess our models' performance effectively. The proposed novel CDK (convolutional neural network, decision tree, K-nearest classifier) ensemble approach for feature extraction is designed to synergize the predictive capabilities of individual models, thereby significantly improving the detection accuracy of OA indicators within radiographic images. We applied several ML and DL approaches to the newly created feature set to evaluate performance. The CDK ensemble model outperformed state-of-the-art studies with a high-performance score of 99.72% accuracy. This remarkable achievement underscores the model's exceptional capability in the early detection of OA, highlighting its superiority in comparison to existing methods.

Response of Bangladesh to the World Health Organization call to eliminate cervical cancer as a public health issue: An observational report.

Background: Despite being preventable, cervical cancer remains a leading cause of mortality among Bangladeshi women. This article addresses the trends in Bangladesh's response to the World Health Organization's (WHO) request for the eradication of cervical cancer within the nation. Discussion: When it comes to cervical cancer, healthcare institutions need to be concerned in terms of protocols for diagnosis and treatment, staff education, and available resources. More than a quarter of all female cancers in Bangladesh are caused by cervical cancer, which can be prevented through better healthcare infrastructure, earlier diagnosis, more qualified healthcare professionals, improved urban and rural hospital infrastructure, community-based clinics, expanded affordable vaccinations, school-based delivery systems, adoption of single-dose vaccine schedules, raising awareness, and compiling a registry of previously affected results. WHO applauds Bangladesh's Ministry of Health and Family Welfare for its efforts to develop the National Strategy for cervical cancer prevention and control, which will guide and strengthen the country's activities to prevent and treat cervical cancer. Conclusion: The endeavor to eradicate this global disease burden should not be limited to Bangladesh; all nations should participate collectively to prevent the malignancy from returning and threatening human civilization.

Understanding patient and family experiences of critical care in Bangladesh and India: What are the priority actions to promote person-centred care?

Patients' experiences in the intensive care unit (ICU) can enhance or impair their subsequent recovery. Improving patient and family experiences on the ICU is an important part of providing high quality care. There is little evidence to guide how to do this in a South Asian critical care context. This study addresses this gap by exploring the experiences of critically ill patients and their families in ICUs in Bangladesh and India. We elicit suggestions for improvements from patients, families and staff and highlight examples of practices that support person-centred care. This multi-site hospital ethnography was carried out in five ICUs in government hospitals in Bangladesh and India, selected using purposive sampling. Qualitative data were collected using non-participant observation and semi-structured interviews and analysed using reflexive thematic analysis. A total of 108 interviews were conducted with patients, families, and ICU staff. Over 1000 hours of observation were carried out across the five study sites. We identified important mediators of patient and family experience that span many different aspects of care. Factors that promote person-centred care include access to ICU for families, support for family involvement in care delivery, clear communication with patients and families, good symptom management for patients, support for rehabilitation, and measures to address the physical, environmental and financial needs of the family. This study has generated a list of recommendations that can be used by policy makers and practitioners who wish to implement person-centred principles in the ICU.

Optimal Treatment of Tumor in Upper Human Respiratory Tract Using Microaerosols.

Lung cancer is a frequently diagnosed respiratory disease caused by particulate matter in the environment, especially among older individuals. For its effective treatment, a promising approach involves administering drug particles through the inhalation route. Multiple studies have investigated the flow behavior of inhaled particles in the respiratory airways of healthy patients. However, the existing literature lacks studies on the precise understanding of the transportation and deposition (TD) of inhaled particles through age-specific, unhealthy respiratory tracts containing a tumor, which can potentially optimize lung cancer treatment. This study aims to investigate the TD of inhaled drug particles within a tumorous, age-specific human respiratory tract. The computational model reports that drug particles within the size range of 5-10 µm are inclined to deposit more on the tumor located in the upper airways of a 70-year-old lung. Conversely, for individuals aged 50 and 60 years, an optimal particle size range for achieving the highest degree of particle deposition onto upper airway tumor falls within the 11-20 µm range. Flow disturbances are found to be at a maximum in the airway downstream of the tumor. Additionally, the impact of varying inhalation flow rates on particle TD is examined. The obtained patterns of airflow distribution and deposition efficiency on the tumor wall for different ages and tumor locations in the upper tracheobronchial airways would be beneficial for developing an efficient and targeted drug delivery system.

Room temperature thermal rectification in suspended asymmetric graphene ribbon.

Thermal rectifiers are essential in optimizing heat dissipation in solid-state devices to enhance energy efficiency, reliability, and overall performance. In this study, we experimentally investigate the thermal rectification phenomenon in suspended asymmetric graphene ribbons (GRs). The asymmetry within the graphene is introduced by incorporating periodic parallel nanoribbons on one side of the GR while maintaining the other side in a pristine form. Our findings reveal a substantial thermal rectification effect in these asymmetric graphene devices, reaching up to 45% at room temperature and increasing further at lower environmental temperatures. This effect is attributed to a significant thermal conductivity contrast between pristine graphene and nanoribbon graphene within the asymmetric structure. We observe that the incorporation of nanoribbons leads to a notable reduction in thermal conductivity, primarily due to phonon scattering and bottleneck effects near the nanoribbon edges. These findings suggest that graphene structures exhibiting asymmetry, facilitated by parallel nanoribbons, hold promise for effective heat management at the nanoscale level and the development of practical phononic devices.

Novel isoniazid-hydrazone derivatives induce cell growth inhibition, cell cycle arrest and apoptosis via mitochondria-dependent caspase activation and PI3K/AKT inhibition.

In this study, seven isoniazid-hydrazone derivatives (3a-g) were synthesized and their structures elucidated by chromatographic techniques, and then the antiproliferative effects of these compounds on various cancer cells were tested. The advanced anticancer mechanism of the most potent compound was then investigated. Antiproliferative activities of the synthesized compounds were evaluated on human breast cancer MCF-7, lung cancer A-549, colon cancer HT-29, and non-cancerous mouse fibroblast 3T3-L1 cell lines by XTT assay. Flow cytometry analysis were carried out to determine cell cycle distribution, apoptosis, mitochondrial membrane potential, multi-caspase activity, and expression of PI3K/AKT signaling pathway. The XTT results showed that all the title molecules displayed cytotoxic activity at varying strengths in different dose ranges, and among them, the strongest cytotoxic effect and high selectivity were exerted by 3d against MCF-7 cells with the IC50 value of 11.35 µM and selectivity index of 8.65. Flow cytometry results revealed that compound 3d induced apoptosis through mitochondrial membrane disruption and multi-caspase activation in MCF-7 cells. It also inhibited the cell proliferation via inhibition of expression of PI3K/AKT and arrested the cell cycle at G0/G1 phase. In conclusion, all these data disclosed that among the synthesized compounds, 3d is notable for in vivo anticancer studies.

Compact metamaterial-based single/double-negative/near-zero index resonator for 5G sub-6 GHz wireless applications.

The concept, performance, and analyses of distinctive, miniaturized metamaterial (MTM) unit cell addressing the forthcoming Sub 6 GHz 5G applications are presented in this paper. Two circular split-ring resonators (CSRR) with two parallel rectangular copper elements in front of the design and a slotted square element in the background make up the suggested metamaterial. It has a line segment with tunable features that is positioned in the center of the little ring copper structure. The suggested design offers a significant operating frequency band of 220 MHz together with a resonance of transmission coefficient S21 at 3.5 GHz. Furthermore, in two (z & x) principal axes of wave propagation, wide-range achievement, single/double-negative (S/DNG) refractive index, negative permittivity, and near-zero permeability properties were demonstrated. Through varying central slotted-strip line length, resonance frequencies can be selectively altered. Moreover, the metamaterial has overall dimensions of 9 × 9 mm2 and is composed on a Rogers 5880 RT substrate. In order to create the suggested MTM's equivalent circuit, which shows similar coefficient of transmission (S21), a proposed design's numerical simulation is carried out in the CST micro-wave studio. This simulation is after that put to comparison with manufacturing of the design.

Model-driven characterization of functional diversity of Pseudomonas aeruginosa clinical isolates with broadly representative phenotypes.

Pseudomonas aeruginosa is a leading cause of infections in immunocompromised individuals and in healthcare settings. This study aims to understand the relationships between phenotypic diversity and the functional metabolic landscape of P. aeruginosa clinical isolates. To better understand the metabolic repertoire of P. aeruginosa in infection, we deeply profiled a representative set from a library of 971 clinical P. aeruginosa isolates with corresponding patient metadata and bacterial phenotypes. The genotypic clustering based on whole-genome sequencing of the isolates, multilocus sequence types, and the phenotypic clustering generated from a multi-parametric analysis were compared to each other to assess the genotype-phenotype correlation. Genome-scale metabolic network reconstructions were developed for each isolate through amendments to an existing PA14 network reconstruction. These network reconstructions show diverse metabolic functionalities and enhance the collective P. aeruginosa pangenome metabolic repertoire. Characterizing this rich set of clinical P. aeruginosa isolates allows for a deeper understanding of the genotypic and metabolic diversity of the pathogen in a clinical setting and lays a foundation for further investigation of the metabolic landscape of this pathogen and host-associated metabolic differences during infection.

Effect of Silencing subolesin and enolase impairs gene expression, engorgement and reproduction in Haemaphysalis longicornis (Acari: Ixodidae) ticks.

IMPORTANCE: Haemaphysalis longicornis is an obligate blood-sucking ectoparasite that has gained attention due its role of transmitting medically and veterinary significant pathogens and it is the most common tick species in Republic of Korea. The preferred strategy for controlling ticks is a multi-antigenic vaccination. Testing the efficiency of a combination antigen is a promising method for creating a tick vaccine. OBJECTIVE: The aim of the current research was to analyze the role of subolesin and enolase in feeding and reproduction of H. longicornis by gene silencing. METHODS: In this study, we used RNA interference to silence salivary enolase and subolesin in H. longicornis. Unfed female ticks injected with double-stranded RNA targeting subolesin and enolase were attached and fed normally on the rabbit's ear. Real-time polymerase chain reaction was used to confirm the extent of knockdown. RESULTS: Ticks in the subolesin or enolase dsRNA groups showed knockdown rates of 80% and 60% respectively. Ticks in the combination dsRNA (subolesin and enolase) group showed an 80% knockdown. Knockdown of subolesin and enolase resulted in significant depletion in feeding, blood engorgement weight, attachment rate, and egg laying. Silencing of both resulted in a significant (p < 0.05) reduction in tick engorgement, egg laying, egg hatching (15%), and reproduction. CONCLUSIONS AND RELEVANCE: Our results suggest that subolesin and enolase are an exciting target for future tick control strategies.