Biobased Nanomaterials: Pioneering Innovations for Biomedical Advancements.

The purpose of this review article is to provide a complete overview of the fastdeveloping topic of biobased nanomaterials and the various uses that they have. An extensive study into the utilization of biological resources for nanotechnology has been motivated by the growing demand for materials that are both sustainable and favorable to the environment. In this review, the different uses of biobased nanomaterials across a variety of fields are investigated. When it comes to drug delivery systems, biosensors, nanocarriers, and catalysts, biobased nanomaterials are interesting choices because of their unique qualities. These properties include biocompatibility, programmable surface chemistry, and inherent functionality. Also, in the biomedical field, biobased nanomaterials offer promising prospects for revolutionizing medical diagnostics and therapies. Their biocompatibility, tunable surface chemistry, and inherent functionalities make them attractive candidates for applications such as targeted drug delivery, imaging contrast agents, and tissue engineering scaffolds. In addition, the study discusses the current difficulties and potential future developments in the industry, emphasizing the necessity of interdisciplinary collaboration and ongoing innovation. The incorporation of nanomaterials derived from biological sources into conventional applications holds tremendous potential for the advancement of sustainable development and provides solutions to global concerns. For the purpose of providing researchers, scientists, and professionals with a complete grasp of the synthesis, characterization, and applications of biobased nanomaterials, the purpose of this review is to serve as a helpful resource.

Discussing pathologic mechanisms of Diabetic retinopathy & therapeutic potentials of curcumin and ß-glucogallin in the management of Diabetic retinopathy.

Diabetic retinopathy (DR) is a form of retinal microangiopathy that occurs as a result of long-term Diabetes mellitus (DM). Patients with Diabetes mellitus typically suffer from DR as a progression of the disease that may be due to initiation and dysregulation of pathways like the polyol, hexosamine, the AGE/RAGE, and the PKC pathway, which all have negative impacts on eye health and vision. In this review, various databases, including PubMed, Google Scholar, Web of Science, and Science Direct, were scoured for data relevant to the aforementioned title. The three most common therapies for DR today are retinal photocoagulation, anti-vascular endothelial growth factor (VEGF) therapy, and vitrectomy, however, there are a number of drawbacks and limits to these methods. So, it is of critical importance and profound interest to discover treatments that may successfully address the pathogenesis of DR. Curcumin and ß-glucogallin are the two potent compounds of natural origin that are already being used in various nutraceutical formulations for several ailments. They have been shown potent antiapoptotic, anti-inflammatory, antioxidant, anticancer, and pro-vascular function benefits in animal experiments. Their parent plant species have been used for generations by practitioners of traditional herbal medicine for the treatment and prevention of various eye ailments. In this review, we will discuss about pathophysiology of Diabetic retinopathy and the therapeutic potentials of curcumin and ß-glucogallin one of the principal compounds from Curcuma longa and Emblica officinalis in Diabetic retinopathy.

Artificial Intelligence in The Management of Neurodegenerative Disorders.

Neurodegenerative disorders are characterized by a gradual but irreversible loss of neurological function. The ability to detect and treat these conditions successfully is crucial for ensuring the best possible quality of life for people who suffer from them. The development of effective new methods for managing and treating neurodegenerative illnesses has been made possible by recent developments in computer technology. In this overview, we take a look at the prospects for applying computational approaches, such as drug design, AI, ML, and DL, to the treatment of neurodegenerative diseases. To review the current state of the field, this article discusses the potential of computational methods for early disease detection, quantifying disease progression, and understanding the underlying biological mechanisms of neurodegenerative diseases, as well as the challenges associated with these approaches and potential future directions. Moreover, it delves into the creation of computational models for the individualization of care for neurodegenerative diseases. The article concludes with suggestions for future studies and clinical applications, highlighting the advantages and disadvantages of using computational techniques in the treatment of neurodegenerative diseases.

Are Proton Pump Inhibitors Contributing in Emerging New Hypertensive Population?

Balancing the therapeutic advantages of a medicine with its possible risks and side effects is an important part of medical practice and drug regulation. When a drug is designed to treat a particular disease or medical condition ends up causing additional risks or side effects that lead to the development of other serious health problems, it can have detrimental consequences for patients. This article explores the correlation between persistent proton pump inhibitor (PPI) use and hypertension, a common cardiovascular ailment. While PPIs are beneficial in treating various gastrointestinal problems, their availability without a prescription has resulted in self-medication and long-term use without medical monitoring. Recent findings have revealed a link between long-term PPI usage and increased cardiovascular risks, particularly hypertension. This study investigates the intricate mechanisms underlying PPI's effects, focusing on potential pathways contributing to hypertension, such as endothelial dysfunction, disruption of nitric oxide bioavailability, vitamin B deficiency, hypocalcemia, and hypomagnesemia. The discussion explains how long-term PPI use can disrupt normal endothelial function, vascular control, and mineral balance, eventually leading to hypertension. The article emphasizes the significance of using PPIs with caution and ongoing research to better understand the implications of these medications on cardiovascular health.

Stochastic modeling and parameter estimation of turbogenerator unit of a thermal power plant under classical and Bayesian inferential framework.

The work reported in present study deals with the development of a novel stochastic model and estimation of parameters to assess reliability characteristics for a turbogenerator unit of thermal power plant under classical and Bayesian frameworks. Turbogenerator unit consists of five components namely turbine lubrication, turbine governing, generator oil system, generator gas system and generator excitation system. The concepts of cold standby redundancy and Weibull distributed random variables are used in development of stochastic model. The shape parameter for all the random variables is same while scale parameter is different. Regenerative point technique and semi-Markov approach are used for evaluation of reliability characteristics. Sufficient repair facility always remains available in plant as well as repair done by the repairman is considered perfect. As the life testing experiments are time consuming, so to highlight the importance of proposed model Monte Carlo simulation study is carried out. A comparative analysis is done between true, classical and Bayesian results of MTSF, availability and profit function.

The pandemic's unseen wounds: COVID-19's profound effects on mental health.

Objective: This review aims to explore the impact of the COVID-19 pandemic on mental health, with a focus on the physiological and psychological consequences, including comorbidities. The goal is to understand the direct and indirect populations affected by mental distress and identify potential interventions. Methodology: A comprehensive literature search was conducted using various databases, including Google Scholar, ResearchGate, ScienceDirect, PubMed, PLoS One, and Web of Science. The search utilized relevant keywords to investigate the direct and indirect impacts of COVID-19 on mental health. The selected articles were critically evaluated and analyzed to identify key findings and insights. Main findings: Mental health, being an intrinsic component of overall well-being, plays a vital role in physiological functioning. The COVID-19 pandemic, caused by the emergence of the novel SARS-CoV-2 virus, has had a devastating global impact. Beyond the respiratory symptoms, individuals recovering from COVID-19 commonly experience additional ailments, such as arrhythmia, depression, anxiety, and fatigue. Healthcare professionals on the frontlines face an elevated risk of mental illness. However, it is crucial to recognize that the general population also grapples with comparable levels of mental distress. Conclusion: The COVID-19 pandemic has underscored the significance of addressing mental health concerns. Various strategies can help mitigate the impact, including counselling, fostering open lines of communication, providing mental support, ensuring comprehensive patient care, and administering appropriate medications. In severe cases, treatment may involve the supplementation of essential vitamins and antidepressant therapy. By understanding the direct and indirect impacts of COVID-19 on mental health, healthcare providers and policymakers can develop targeted interventions to support individuals and communities affected by the pandemic. Continued research and collaborative efforts are essential to address this pervasive issue effectively.

Comparison of the Quality of Life Among the Immediate Loading Implant Overdentures Using the Single and the Double Implants: An Original Study.

Introduction: In edentulous individuals, single implant-retained mandibular overdentures are an effective substitute for double implant-retained overdentures. In this current research, the oral health-related quality of life (OHRQoL) was assessed for the immediate loading overdenture using the implants. The comparisons are drawn between the single and double implants. Materials and Methods: Forty subjects received single and double implants for the placement of the mandibular overdentures. Within a week days of implant insertion, they were loaded with overdentures. Using the Oral Health Impact Profile-14 (OHIP-14) questionnaire, the OHRQoL was measured before treatment, one month following treatment, and 12 months thereafter. Results: In both the single implant and double implant groups, participants' mean OHIP-14 scores decreased statistically significantly for the different timelines. For the single implant group, the baseline total mean OHIP-14 score was 14.33, and for double implants, it was 19.15. Following therapy, it decreased to 8.55 in the single implant group and 9.48 for the double implant group at one month, and at 12 months, it further decreased to 3.25 in the single implant group while it was 5.15 in the double implant group. Conclusions: Single and double implants increase the QoL for older subjects who are edentulous at the 1-month and 1-year recall points. When two implants are used by older individuals, the single implant might offer an equivalent quality of life.

Comparison of Cumulative Live Birth Rate (CLBR) According to Patient Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) Stratification Among Low Prognosis Women Undergoing IVF-ICSI Cycles.

Background: The purpose of the current study was to evaluate patient-oriented strategies encompassing individualized oocyte number (POSEIDON) criteria, validate stratification of low prognosis women, and prognosticate their reproductive potential in terms of cumulative live birth rate (CLBR) in Indian women. Methods: Out of 4048 women who underwent IVF/ICSI, 3287 women met the criteria for final evaluation of CLBR. They criteria were divided into (a) group 1a as cases with <4 oocytes retrieved and 1b with 4-9 oocytes retrieved; (b) group 2a as cases with <4 oocytes retrieved and 2b with 4-9 oocytes retrieved; (c) group 3 (<35 years, AMH <1.2 ng/ml, AFC <5); and (d) group 4 (≥35 years, AMH <1.2 ng/ml, AFC <5). Non-POSEIDON group was sub-divided into normo-responders (10-20 oocytes) and hyper-responder (>20 oocytes). Results: Overall CLBR was two-fold lower in POSEIDON group as compared to non-POSEIDON group (p<0.001). For every one-year increase in the age, the odds of CLBR decreased by 4% (OR 0.96, CI 0.93-0.99) in POSEIDON group and by 5% (OR 0.95, CI 0.92-0.98) in non-POSEIDON group. For every unit increase in number of oocytes retrieved, the odds of CLBR increased by 1.22 times (OR1.22, CI 1.16-1.28) in POSEIDON group and by 1.08 times (OR 1.08, CI 1.05-1.11) in non-POSEIDON group. Among POSEIDON groups, the highest values in CLBR belonged to group 1b followed by 3, 2b, 4, 1a, and 2a. Conclusion: POSEIDON stratification of low-prognosis women undergoing IVF may be considered valid to prognosticate and counsel women undergoing IVF. Prospective studies will strengthen its validity among different ethnic populations.

Availability optimization of power generating units used in sewage treatment plants using metaheuristic techniques.

Metaheuristic techniques have been utilized extensively to predict industrial systems' optimum availability. This prediction phenomenon is known as the NP-hard problem. Though, most of the existing methods fail to attain the optimal solution due to several limitations like slow rate of convergence, weak computational speed, stuck in local optima, etc. Consequently, in the present study, an effort has been made to develop a novel mathematical model for power generating units assembled in sewage treatment plants. Markov birth-death process is adopted for model development and generation of Chapman-Kolmogorov differential-difference equations. The global solution is discovered using metaheuristic techniques, namely genetic algorithm and particle swarm optimization. All time-dependent random variables associated with failure rates are considered exponentially distributed, while repair rates follow the arbitrary distribution. The repair and switch devices are perfect and random variables are independent. The numerical results of system availability have been derived for different values of crossover, mutation, several generations, damping ratio, and population size to attain optimum value. The results were also shared with plant personnel. Statistical investigation of availability results justifies that particle swarm optimization outdoes genetic algorithm in predicting the availability of power-generating systems. In present study a Markov model is proposed and optimized for performance evaluation of sewage treatment plant. The developed model is one that can be useful for sewage treatment plant designers in establishing new plants and purposing maintenance policies. The same procedure of performance optimization can be adopted in other process industries too.

Targeting an essential Plasmodium cold shock protein to block growth and transmission of malaria parasite.

Cold shock proteins are characterized by the presence of one or more cold shock domains that bestow them with nucleic acid binding ability. Although cold shock proteins are well characterized in bacteria, plants and humans, there is no information on their existence and role in malaria parasite. Here, we have identified and delineated the function of a cold shock protein of Plasmodium falciparum (Pf) 'PfCoSP'. We demonstrate that PfCoSP exhibits nucleic acid binding properties and regulates gene expression. PfCoSP promotes microtubule assembly by interacting with Pf α/ß tubulin. We identified a human cold shock protein LIN28A inhibitor 'LI71' as a binding partner of PfCoSP which inhibited PfCoSP-DNA and α/ß tubulin interactions and, also inhibited the development of asexual blood stages and gametocyte stage of malaria parasite. Because PfCoSP is essential for parasite survival, characterization of its interacting partners may form the basis for development of future anti-malarials.

Characterization of Plasmodium falciparum prohibitins as novel targets to block infection in humans by impairing the growth and transmission of the parasite.

Prohibitins (PHBs) are highly conserved pleiotropic proteins as they have been shown to mediate key cellular functions. Here, we characterize PHBs encoding putative genes ofPlasmodium falciparum by exploiting different orthologous models. We demonstrated that PfPHB1 (PF3D7_0829200) and PfPHB2 (PF3D7_1014700) are expressed in asexual and sexual blood stages of the parasite. Immunostaining indicated hese proteins as mitochondrial residents as they were found to be localized as branched structures. We further validated PfPHBs as organellar proteins residing in Plasmodium mitochondria, where they interact with each other. Functional characterization was done in Saccharomyces cerevisiae orthologous model by expressing PfPHB1 and PfPHB2 in cells harboring respective mutants. The PfPHBs functionally complemented the yeast PHB1 and PHB2 mutants, where the proteins were found to be involved in stabilizing the mitochondrial DNA, retaining mitochondrial integrity and rescuing yeast cell growth. Further, Rocaglamide (Roc-A), a known inhibitor of PHBs and anti-cancerous agent, was tested against PfPHBs and as an antimalarial. Roc-A treatment retarded the growth of PHB1, PHB2, and ethidium bromide petite yeast mutants. Moreover, Roc-A inhibited growth of yeast PHBs mutants that were functionally complemented with PfPHBs, validating P. falciparum PHBs as one of the molecular targets for Roc-A. Roc-A treatment led to growth inhibition of artemisinin-sensitive (3D7), artemisinin-resistant (R539T) and chloroquine-resistant (RKL-9) parasites in nanomolar ranges. The compound was able to retard gametocyte and oocyst growth with significant morphological aberrations. Based on our findings, we propose the presence of functional mitochondrial PfPHB1 and PfPHB2 in P. falciparum and their druggability to block parasite growth.

In vitro fertilization as an independent risk factor for perinatal complications: Single-center 10 years cohort study.

OBJECTIVES: Assisted Reproductive Technology (ART) has made great strides in the past forty-years, but no medical treatment comes without side effects. Despite several studies reporting high incidences of perinatal complications, the association is inconclusive. Also, the effect of racially and ethnically distinguished Asian population undergoing ART on perinatal outcomes is not well studied. Therefore, this study attempts to compare various perinatal outcome parameters in ART, and spontaneously conceived singleton pregnancies from a single high-volume tertiary care center. METHODS: This is a retrospective cohort study from a single tertiary infertility center, carried out from January 2011 to September 2020. The study included 1,125 IVF conceived babies (AB group) and 7,193 spontaneous conceived babies (SB group). The groups were compared using the Pearson Chi-square test and adjusted odds ratio, calculated using the multivariate analysis. RESULTS: Most of the perinatal complications, such as preterm birth (PTB), early preterm birth, low birth weight (LBW), extremely low birth weight, small for gestational age, large for gestational age babies, neonatal intensive care unit (NICU) admission, need for surfactant, meconium aspiration syndrome, neonatal seizures, intraventricular hemorrhage, hypoxic-ischemic encephalopathy, and patent ductus arteriosus was significantly increased in the AB group when compared to the SB group (p<0.05). In-vitro fertilization (IVF) independently increases the risk of LBW (aOR 2.530; 95% CI 2.194-2.917), PTB (aOR 4.004; 95% CI 3.496-4.587), NICU admission (aOR 2.003; 95% CI 1.610-2.492) and neonatal seizures (aOR 9.805; 95% CI 5.755-16.706).Conclusions: All ART-conceived pregnant patients should receive antenatal counselling regarding perinatal complications and should deliver at a tertiary care center with appropriate NICU support.

Host-Erythrocytic Sphingosine-1-Phosphate Regulates Plasmodium Histone Deacetylase Activity and Exhibits Epigenetic Control over Cell Death and Differentiation.

The evolution of resistance to practically all antimalarial drugs poses a challenge to the current malaria elimination and eradication efforts. Given that the epigenome of Plasmodium falciparum governs several crucial parasite functions, pharmaceutical interventions with transmission-blocking potential that target epigenetic molecular markers and regulatory mechanisms are likely to encounter drug resistance. In the malaria parasite, histone deacetylases (HDACs) are essential epigenetic modulators that regulate cellular transcriptional rearrangements, notably the molecular mechanisms underlying parasite proliferation and differentiation. We establish "lipid sequestration" as a mechanism by which sphingolipids, specifically Sphingosine-1-Phosphate (S1P) (a metabolic product of Sphingosine Kinase 1 [SphK-1]), regulate epigenetic reprogramming in the parasite by interacting with, and modulating, the histone-deacetylation activity of PfHDAC-1, thereby regulating Plasmodium pathogenesis. Furthermore, we demonstrate that altering host S1P levels with PF-543, a potent and selective Sphk-1 inhibitor, dysregulates PfHDAC-1 activity, resulting in a significant increase in the global histone acetylation signals and, consequently, transcriptional modulation of genes associated with gametocytogenesis, virulence, and proliferation. Our findings point to a hitherto unrecognized functional role for host S1P-mediated sphingolipid signaling in modulating PfHDAC-1's enzymatic activity and, as a result, the parasite's dynamic genome-wide transcriptional patterns. The epigenetic regulation of parasite proliferation and sexual differentiation offers a novel approach for developing host-targeted therapeutics to combat malaria resistance to conventional regimens. IMPORTANCE Sphingolipid is an 18-carbon amino-alcohol-containing lipid with a sphingosine backbone, which when phosphorylated by sphingosine kinase 1 (SphK-1), generates sphingosine-1-phosphate (S1P), an essential lipid signaling molecule. Dysregulation of S1P function has been observed in a variety of pathologies, including severe malaria. The malaria parasite Plasmodium acquires a host S1P pool for its growth and survival. Here, we describe the molecular attuning of histone deacetylase-1 (PfHDAC-1), a crucial epigenetic modulator that contributes to the establishment of epigenetic chromatin states and parasite survival, in response to S1P binding. Our findings highlight the host lipid-mediated epigenetic regulation of malaria parasite key genes.

Novel targets for potential therapeutic use in Diabetes mellitus.

Future targets are a promising prospect to overcome the limitation of conventional and current approaches by providing secure and effective treatment without compromising patient compliance. Diabetes mellitus is a fast-growing problem that has been raised worldwide, from 4% to 6.4% (around 285 million people) in past 30 years. This number may increase to 430 million people in the coming years if there is no better treatment or cure is available. Ageing, obesity and sedentary lifestyle are the key reasons for the worsening of this disease. It always had been a vital challenge, to explore new treatment which could safely and effectively manage diabetes mellitus without compromising patient compliance. Researchers are regularly trying to find out the permanent treatment of this chronic and life threatening disease. In this journey, there are various treatments available in market to manage diabetes mellitus such as insulin, GLP-1 agonist, biguanides, sulphonyl ureas, glinides, thiazolidinediones targeting the receptors which are discovered decade before. PPAR, GIP, FFA1, melatonin are the recent targets that already in the focus for developing new therapies in the treatment of diabetes. Inspite of numerous preclinical studies very few clinical data available due to which this process is in its initial phase. The review also focuses on the receptors like GPCR 119, GPER, Vaspin, Metrnl, Fetuin-A that have role in insulin regulation and have potential to become future targets in treatment for diabetes that may be effective and safer as compared to the conventional and current treatment approaches.

Comparison of Weight for Height and BMI for Age for Estimating Overnutrition Burden in Under-Five Populations With High Stunting Prevalence.

BACKGROUND: Overnourished under-five children are anthro-pometrically classified as either being at possible risk of over-weight, overweight or obese and defined so, when either weight for height or body mass index for age (BMI-for-age) are >1SD to 2SD, >2SD to 3SD and >3SD, respectively of the analogous World Health Organization standards. AIM: To compare weight for height and BMI for age definitions for quantifying overnutrition burden. METHODS: Theoretical consequences of ignoring age were evaluated by comparing, at varying height for age z-scores, the age- and sex-specific cutoffs of BMI that would define overnutrition with these two metrics. Overnutrition prevalence was then compared in simulated populations (short, intermediate and tall) and real-life datasets from India. RESULTS: In short (-2SD) children, the BMI cutoffs with weight for height criteria were lower in comparison to BMI for age till 7-8 months, but higher at later ages. In National Family Health Survey-4, India dataset (short population), overnutrition (>1SD) prevalence with weight for height was higher from 0-0.5 years (exclusive breastfeeding age), but lower at subsequent ages. The prevalence difference (weight for height - BMI for age) in 0.5-5 years was -2.26% (6.57% vs 8.83%); this attenuated in 0-5 years (-1.55%; 7.23% vs 8.78%). The discrepancy was maxi-mal for stunted children and was lower in girls. A similar pattern, of lower magnitude, was observed for overweight (>2SD) com-parison. In intermediate and tall populations, there were no meaningful differences. CONCLUSION: The two definitions produce cutoffs, and hence estimates of overnutrition, that differ with the age, sex, and height of under-five children. The relative invariance, with age and height, of BMI for age, favors its use.

Development of Mitochondria Targeting AIE-Active Cyclometalated Iridium Complexes as Potent Antimalarial Agents.

The emergence of resistance to conventional antimalarial treatments remains a major cause for concern. New drugs that target the distinct development stages of Plasmodium parasites are required to address this risk. Herein, water-soluble aggregation-induced emission active cyclometalated iridium(III) polypyridyl complexes (Ir1-Ir12) are developed for the elimination of malaria parasites. Remarkably, these complexes show potent antimalarial activity in low nanomolar range against 3D7 (chloroquine and artemisinin sensitive strain), RKL9 (chloroquine resistant strain), and R539T (artemisinin resistant strains) strains of Plasmodium falciparum with faster killing rate of malaria parasites. Concomitantly, these complexes exhibit efficient in vivo antimalarial activity against both the asexual and gametocyte stages of Plasmodium berghei malaria parasite, suggesting promising transmission-blocking potential. The complexes tend to localize into mitochondria of P. falciparum determined by image and cell-based assay. The mechanistic studies reveal that these complexes exert their antimalarial activity by increasing reactive oxygen species levels and disrupting its mitochondrial membrane potential. Furthermore, the mitochondrial-dependent antimalarial activity of these complexes is confirmed in yeast model. Thus, this study for the first time highlights the potential role of targeting P. falciparum mitochondria by iridium complexes in discovering and developing the next-generation antimalarial agents for treating multidrug resistant malaria parasites.

Perspective of educational environment on students' perception of teaching and learning.

Cross-sectional research was designed using the Dundee Ready Education Environment Measure (DREEM) to examine the impact of the educational environment on students' perceptions of learning and teaching in a university offering higher education. Using a Likert scale, 300 participants from various streams were assessed. There were no disparities in the students' judgments in the five DREEM categories of discipline, accommodation, gender, level of study, and disciplines. In general, students judged that the student-teaching environment was satisfactory. To investigate the validity of the DREEM, we conducted Cronbach alpha analysis and exploratory factor analysis (EFA) employing principal component analysis with varimax rotation. Only 44 of the 50 factors were deemed to be significant, with a cumulative explained variance of 46.539%. The total construct dependability of the EFA nine-factor solutions was 0.954. Finally, only five acceptable factors explained 46.539% variance using the criteria of eigenvalue > 1 and Cronbach's alpha > 0.6. Factor analysis was appropriate as evidenced by the Kaiser-Meyer-Olkin Measure of Sampling Adequacy of 0.942. With a Cronbach alpha of 0.955, the revised first domain of "student perception of learning" was the most trustworthy DREEM item, accounting for 20.19% of the variance. The highest factor loading was for the item "Teaching helps me become a more active learner". A redesigned DREEM might be valuable for assessing the educational environment at institutions providing higher education.

Antimalarial and Plasmodium falciparum serpentine receptor 12 targeting effect of FDA approved purinergic receptor antagonist.

Intraerythrocytic stages of Plasmodium falciparum responsible for all clinical manifestations of malaria are regulated by array of signalling cascades that represent attractive targets for antimalarial therapy. G-protein coupled receptors (GPCRs) are druggable targets in the treatment of various pathological conditions, however, there is limited understanding about the role of GPCRs in malaria pathogenesis. In Plasmodium, serpentine receptors (PfSR1, PfSR10, PfSR12 and PfSR25) with GPCR-like membrane topology have been reported with the finite knowledge about their potential as antimalarial targets. We analyzed the localization of these receptors in malaria parasite by immunofluorescence assays. All four receptors were expressed in blood stages with PfSR12 expressing more in late intraerythrocytic stages. Further, we evaluated the druggability of PfSR12 using FDA-approved P2Y purinergic receptor antagonist, Prasugrel and its active metabolite R138727, which is proposed to be specific towards PfSR12. Interestingly, biophysical analysis indicated strong binding between PfSR12 and R138727 as compared to the prodrug Prasugrel. This binding interaction was further confirmed by thermal shift assay. Treatment of parasite with Prasugrel and R138727 resulted in growth inhibition of P. falciparum indicating an important role of purinergic signalling and PfSR12 in parasite survival. Next, progression studies indicated the inhibitory effect of Prasugrel begins in late erythrocyte stages corroborating with PfSR12 expression at these stages. Furthermore, Prasugrel also blocked in vivo growth of malaria parasite in a mouse experimental model. This study indicates the presence of P2Y type of purinergic signalling in growth and development of malaria parasite and suggests PfSR12, putative purinergic receptor druggability through Prasugrel.Communicated by Ramaswamy H. Sarma.

Optimum estimator in simple random sampling using two auxiliary attributes with application in agriculture, fisheries and education sectors.

In modern age of information technology, data is available everywhere in huge amount. Every sector generates lot of data every day. The investigation of each unit of data is not feasible due to limited resources like time, labor, and cost. In such situations, survey sampling is recommended to draw the information about the population parameters. Therefore, the main objective of present study is to develop an estimation method for obtaining the information about population parameter. We propose an optimum estimator for enhanced estimation of population mean in simple random sampling by utilizing the information of the two auxiliary attribute. The expression for bias, mean squared error (MSE) and minimum mean squared error of the proposed estimator are derived up to the first order of approximation and it is shown that the proposed estimator under derived conditions perform better than the existing estimators theoretically. Four population are demonstrated to assess the performance as well as applicability of the proposed estimator. The percentage relative efficiency (PRE) of proposed estimator for all the populations is 209.533, 163.852, 210.398 and 340.578, respectively. The numerical illustrations confirm that the proposed estimator dominates over the existing estimators.•The main objective of present study is to propose a new estimator/method for estimation of population mean using two auxiliary attributes under simple random sampling.•The bias and mean square error of the proposed estimator/method is derived and compared with the existing estimators to compare the efficiency theoretically.•Applications of the proposed method/estimator is highlighted using thorough the real data sets of various sectors.