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Covering: up to June 2024 Benzylisoquinoline alkaloids (BIAs) represent a diverse class of plant specialized metabolites derived from L -tyrosine, exhibiting significant pharmacological properties such as anti-microbial, anti-spasmodic, anti-cancer, cardiovascular protection, and analgesic effects. The industrial production of valuable BIAs relies on extraction from plants; however, challenges concerning their low concentration and efficiency hinder drug development. Hence, alternative approaches, including biosynthesis and chemoenzymatic synthesis, have been explored. Model species like Papaver somniferum and Coptis japonica have played a key role in unraveling the biosynthetic pathways of BIAs; however, many aspects, particularly modified steps like oxidation and methylation, remain unclear. Critical enzymes, e.g., CYP450s and methyltransferases, play a substantial role in BIA backbone formation and modification, which is essential for understanding the origin and adaptive evolution of these plant specialized metabolites. This review comprehensively analyzes the structural diversity of reported BIAs and their distribution in plant lineages. In addition, the progress in understanding biosynthesis, evolution, and catalytic mechanisms underlying BIA biosynthesis is summarized. Finally, we discuss the progress and challenges in metabolic engineering, providing valuable insights into BIA drug development and the sustainable utilization of BIA-producing plants. [ABSTRACT FROM AUTHOR]

Background: α-Hairpinins are a family of antimicrobial peptides, promising antimicrobial agents, which includes only 12 currently revealed members with proven activity, although their real number is supposed to be much higher. α-Hairpinins are short peptides containing four cysteine residues arranged in a specific Cys-motif. These antimicrobial peptides (AMPs) have a characteristic helix−loop−helix structure with two disulfide bonds. Isolation of α-hairpinins by biochemical methods is cost- and labor-consuming, thus requiring reliable preliminary in silico prediction. Methods: In this study, we developed a special algorithm for the prediction of putative α-hairpinins on the basis of characteristic motifs with four (4C) and six (6C) cysteines deduced from translated plant transcriptome sequences. We integrated this algorithm into the Cysmotif searcher pipeline and then analyzed all transcriptomes available from the One Thousand Plant Transcriptomes project. Results: We predicted more than 2000 putative α-hairpinins belonging to various plant sources including algae, mosses, ferns, and true flowering plants. These data make α-hairpinins one of the ubiquitous antimicrobial peptides, being widespread among various plants. The largest numbers of α-hairpinins were revealed in the Papaveraceae family and in Papaver somniferum in particular. Conclusions: By analyzing the primary structure of α-hairpinins, we concluded that more predicted peptides with the 6C motif are likely to have potent antimicrobial activity in comparison to the ones possessing 4C motifs. In addition, we found 30 α-hairpinin precursors containing from two to eight Cys-rich modules. A striking similarity between some α-hairpinin modules belonging to diverse plants was revealed. These data allowed us to assume that the evolution of α-hairpinin precursors possibly involved changing the number of Cys-rich modules, leading to some missing middle and C-terminal modules, in particular. [ABSTRACT FROM AUTHOR]

The evolution of morphinan alkaloid biosynthesis in plants of the genus Papaver includes permutation of several processes including gene duplication, fusion, neofunctionalization, and deletion resulting in the present chemotaxonomy. A critical gene fusion event resulting in the key bifunctional enzyme reticuline epimerase (REPI), which catalyzes the stereochemical inversion of (S)-reticuline, was suggested to precede neofunctionalization of downstream enzymes leading to morphine biosynthesis in opium poppy (Papaver somniferum). The ancestrally related aldo-keto reductases 1,2-dehydroreticuline reductase (DRR), which occurs in some species as a component of REPI, and codeinone reductase (COR) catalyze the second and penultimate steps, respectively, in the pathway converting (S)-reticuline to morphine. Orthologs for each enzyme isolated from the transcriptomes of 12 Papaver species were shown to catalyze their respective reactions in species that capture states of the metabolic pathway prior to key evolutionary events, including the gene fusion event leading to REPI, thus suggesting a patchwork model for pathway evolution. Analysis of the structure and substrate preferences of DRR orthologs in comparison with COR orthologs revealed structure-function relationships underpinning the functional latency of DRR and COR orthologs in the genus Papaver, thus providing insights into the molecular events leading to the evolution of the pathway. Conservation across the Papaver genus of two aldo-keto reductases catalyzing the second and penultimate steps in morphine biosynthesis reveals the latent activity of several enzymes and suggests a patchwork model of pathway evolution in opium poppy. [ABSTRACT FROM AUTHOR]

Key Clinical Message: The poppy seed test is a valuable, cost‐effective, and sensitive initial diagnostic investigation to identify the presence of colovesical fistula, particularly for clinicians in remote or rural areas with lack of access to specialist radiologic, endoscopic, surgical, or urological support. The poppy seed test therefore may act as a bridge toward the commencement of appropriate referral pathways for the management of colovesical fistula. The diagnosis of colovesical fistula is resource intensive, often requiring a combination of radiological investigation and endoscopy. The poppy seed test is a non‐invasive and cost‐effective alternative that has been demonstrated to identify presence of colovesical fistula with high sensitivity. There is however a noticeable paucity of recommendations for the poppy seed test in the diagnostic approach to colovesical fistula due to significant advancements in alternative radiologic and endoscopic technologies. Despite this, in resource‐challenged areas with lack of specialist support, the poppy seed test is a cost‐effective, accessible and safe test that can be performed to confirm the presence of colovesical fistula. We report a case of a 79‐year‐old man with a past history of colorectal cancer managed surgically with adjuvant chemoradiotherapy who develops noisy micturition, pneumaturia, and fecaluria 22 years after treatment. Given the suspicion of colovesical fistula, computed tomography imaging and cystoscopy were performed which was unable to demonstrate an overt fistula. The poppy seed test was utilized and demonstrated presence of poppy seeds in the urine, confirming the presence of a fistula. The patient was referred to a specialist surgical center for consideration of further management. The poppy seed test is a valuable initial diagnostic investigation for clinicians in remote or rural areas with lack of access to specialist radiologic, endoscopic, surgical, or urological support in confirming the presence of a colovesical fistula and initiating referral pathways for the management of this condition. [ABSTRACT FROM AUTHOR]

Abstract Among plant-derived secondary metabolites are benzylisoquinoline alkaloids (BIAs) that play a vital role in medicine. The most conspicuous BIAs frequently found in opium poppy are morphine, codeine, thebaine, papaverine, sanguinarine, and noscapine. BIAs have provided abundant clinically useful drugs used in the treatment of various diseases and ailments With an increasing demand for these herbal remedies, genetic improvement of poppy plants appears to be essential to live up to the expectations of the pharmaceutical industry. With the advent of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated9 (Cas9), the field of metabolic engineering has undergone a paradigm shift in its approach due to its appealing attributes, such as the transgene-free editing capability, precision, selectivity, robustness, and versatility. The potentiality of the CRISPR system for manipulating metabolic pathways in opium poppy was demonstrated, but further investigations regarding the use of CRISPR in BIA pathway engineering should be undertaken to develop opium poppy into a bioreactor synthesizing BIAs at the industrial-scale levels. In this regard, the recruitment of RNA-guided genome editing for knocking out miRNAs, flower responsible genes, genes involved in competitive pathways, and base editing are described. The approaches presented here have never been suggested or applied in opium poppy so far.

Herbal medicines were widely used in ancient and modern societies as remedies for human ailments. Notably, the Papaveraceae family includes well-known species, such as Papaver somniferum and Chelidonium majus , which possess medicinal properties due to their latex content. Latex-bearing plants are a rich source of diverse bioactive compounds, with applications ranging from narcotics to analgesics and relaxants. With the advent of high-throughput technologies and advancements in sequencing tools, an opportunity exists to bridge the knowledge gap between the genetic information of herbs and the regulatory networks underlying their medicinal activities. This emerging discipline, known as herbgenomics, combines genomic information with other -omics studies to unravel the genetic foundations, including essential gene functions and secondary metabolite biosynthesis pathways. Furthermore, exploring the genomes of various medicinal plants enables the utilization of modern genetic manipulation techniques, such as Clustered Regularly-Interspaced Short Palindromic Repeats (CRISPR/Cas9) or RNA interference. This technological revolution has facilitated systematic studies of model herbs, targeted breeding of medicinal plants, the establishment of gene banks and the adoption of synthetic biology approaches. In this article, we provide a comprehensive overview of the recent advances in genomic, transcriptomic, proteomic and metabolomic research on species within the Papaveraceae family. Additionally, it briefly explores the potential applications and key opportunities offered by the -omics perspective in the pharmaceutical industry and the agrobiotechnology field. [ABSTRACT FROM AUTHOR]

Several proteins from plant pathogenesis‐related family 10 (PR10) are highly abundant in the latex of opium poppy and have recently been shown to play diverse and important roles in the biosynthesis of benzylisoquinoline alkaloids (BIAs). The recent determination of the first crystal structures of PR10‐10 showed how large conformational changes in a surface loop and adjacent β‐strand are coupled to the binding of BIA compounds to the central hydrophobic binding pocket. A more detailed analysis of these conformational changes is now reported to further clarify how ligand binding is coupled to the formation and cleavage of an intermolecular disulfide bond that is only sterically allowed when the BIA binding pocket is empty. To decouple ligand binding from disulfide‐bond formation, each of the two highly conserved cysteine residues (Cys59 and Cys155) in PR10‐10 was replaced with serine using site‐directed mutagenesis. Crystal structures of the Cys59Ser mutant were determined in the presence of papaverine and in the absence of exogenous BIA compounds. A crystal structure of the Cys155Ser mutant was also determined in the absence of exogenous BIA compounds. All three of these crystal structures reveal conformations similar to that of wild‐type PR10‐10 with bound BIA compounds. In the absence of exogenous BIA compounds, the Cys59Ser and Cys155Ser mutants appear to bind an unidentified ligand or mixture of ligands that was presumably introduced during expression of the proteins in Escherichia coli. The analysis of conformational changes triggered by the binding of BIA compounds suggests a molecular mechanism coupling ligand binding to the disruption of an intermolecular disulfide bond. This mechanism may be involved in the regulation of biosynthetic reactions in plants and possibly other organisms. [ABSTRACT FROM AUTHOR]

Opium poppy, coca and cannabis are raw materials for three notorious illicit drugs. For a long time, drug lords have been growing and smuggling these drugs in a variety of ways and channels and are continually finding new ways of trafficking their wares, which has led to the increasing difficulty of global drug enforcement. In the present paper, we propose an innovative pollen identification system for these important drug plants, which provides a tool for screening and detection of the drugs to aid in drug enforcement. By utilizing the characteristics of these fine particles, their abundant production, and high resistance to decay, we believe this tool could be applied in the following scenarios: detecting and dynamically monitoring drug cultivation activities; determining whether a suspect has been to fields of drug plants and determining whether the site has ever been planted with a drug plant and/or was involved in drug production. In the future, combined with microscope automatic image acquisition technology and intelligent image recognition technology, this pollen identification system is expected to be used to screen three notorious illicit drug plants, thus enhancing the efficiency of drug related crime investigations. [ABSTRACT FROM AUTHOR]

Opium poppy is a plant used in both the pharmaceutical and food industries. Substances found on the surface of dry poppy seeds belong to the group of opium alkaloids. However, the presence of these substances in food products poses a risk to consumer health, which is why new permissible levels for both substances in poppy seeds and derivative products have been introduced in Regulation (EU) 2023/915. This research aimed to analyze the content of all six opium alkaloids in poppy seeds provided directly by producers as well as those available on the local market in Poland. The research confirmed the presence of morphine in all examined poppy seed samples. The alkaloid content ranged from 12.46 to 102.86 mg/kg for seeds purchased in local markets and from 1.1 to 110.1 mg/kg for seeds obtained directly from producers. Both groups showed similar levels of morphine content as well as other OAs, which significantly exceeded the permissible limit of 20 mg/kg set by the European Commission (EU) 2023/915. These results indicate that the presence of morphine and other opium alkaloids in poppy seeds exceeds permissible levels, posing a serious health issue and necessitating further research and improvement in processing methods. [ABSTRACT FROM AUTHOR]

Purpose: This two-treatment. four-period, double-blind, randomized controlled crossover trial assessed the ability of two denture adhesives, both applied with a thin nozzle in a continuous application pattern, to prevent food infiltration beneath partial dentures. Methods: Participants with mandibular partial dentures and a history of food particle infiltration were enrolled. All participants used both an optimized Calcium/zinc partial salt of polyvinyl methyl ether/maleic acid (PVM/MA) denture adhesive and a calcium/sodium partial salt of PVM/MA test denture adhesive, twice each, throughout four study periods, according to a randomly assigned sequence. At each visit, participants underwent two assessments: once with no denture adhesive (baseline) and once with denture adhesive, 1 hour after adhesive application. For each assessment, participants ate one-half of the top of a poppy seed muffin, and a dental professional counted the seeds retained on the denture and mucosa. which was the primary variable. The change-frombaseline comparison was made for each treatment separately using a paired t-test or Wilcoxon Signed Rank test depending on the normality of the data. A between-treatment comparison for the change from baseline was performed using a crossover ANCOVA with treatment and period as fixed effects and participant as a random effect. The baseline poppy seed count was used as a covariate. Results: 30 participants were enrolled: 29 completed the trial. Both denture adhesives achieved statistically significantly fewer retained seeds versus baseline (P< 0.001). The calcium/zinc adhesive reduced the seed count from baseline by 85.9% (6.18 vs 0.86). and the calcium/sodium adhesive reduced seed count by 76.6% (6.04 vs 1.43). Comparing the two denture adhesives. the reduction in seed count from baseline was statistically significantly greater for the calcium/zinc adhesive versus the calcium/sodium formulation (P = 0. 008). [ABSTRACT FROM AUTHOR]

Among plant-derived secondary metabolites are benzylisoquinoline alkaloids (BIAs) that play a vital role in medicine. The most conspicuous BIAs frequently found in opium poppy are morphine, codeine, thebaine, papaverine, sanguinarine, and noscapine. BIAs have provided abundant clinically useful drugs used in the treatment of various diseases and ailments With an increasing demand for these herbal remedies, genetic improvement of poppy plants appears to be essential to live up to the expectations of the pharmaceutical industry. With the advent of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated9 (Cas9), the field of metabolic engineering has undergone a paradigm shift in its approach due to its appealing attributes, such as the transgene-free editing capability, precision, selectivity, robustness, and versatility. The potentiality of the CRISPR system for manipulating metabolic pathways in opium poppy was demonstrated, but further investigations regarding the use of CRISPR in BIA pathway engineering should be undertaken to develop opium poppy into a bioreactor synthesizing BIAs at the industrial-scale levels. In this regard, the recruitment of RNA-guided genome editing for knocking out miRNAs, flower responsible genes, genes involved in competitive pathways, and base editing are described. The approaches presented here have never been suggested or applied in opium poppy so far. [ABSTRACT FROM AUTHOR]

Drawing on long-term fieldwork in Badakhshan, a borderland province in the northeast of Afghanistan, the paper explores the role that opium poppy cultivation has played in a marginal high-altitude economy. Framed by the analytic of 'narco-frontiers' and the puzzle of the persistence of small farmers in uneven agrarian transitions, the paper investigates the diversity of market and non-market institutions that operate across the means of production of opium. Rather than seeing opium poppy production as the vanguard of an agrarian transition, it is suggested that it is more of a rearguard action to ensure survival. [ABSTRACT FROM AUTHOR]

This article presents a case study involving a 72-year-old woman who tested positive for codeine and morphine on a urine drug screen. The patient claimed to have not taken any nonprescribed medications and requested copies of the test results. It was later discovered that her positive result may have been caused by the consumption of poppy seeds in her breakfast. The article explores the distinction between codeine ingestion and poppy seed consumption as the cause of a positive drug test result. It emphasizes the importance of clear communication between the laboratory and practitioners, accurate reporting of results, and patient advocacy in reviewing medical records for accuracy. The article concludes with educational points, including the fact that poppy seed-containing food can cause a positive opiates result in urine and that previous guidelines for interpreting opiates results are no longer valid. [Extracted from the article]

Thebaine, a vital precursor in the codeine and morphine pathway, shows promise in addiction treatment. We conducted a comprehensive study on the thebaine biosynthesis pathway in opium poppy, utilizing bioinformatics tools. The dataset comprising the thirteen genes associated with the thebaine biosynthesis pathway was compiled from an extensive review of published literature and validated using the NCBI BLAST tool. Utilizing STRING and Cytoscape, we analyzed gene interactions and visualized the molecular interaction network, respectively. To identify hub proteins, CytoHubba was administered. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) at STRING were used for the enrichment analysis of the hub genes. CytoCluster was used to analyze the network in clusters. Promoter regions of hub genes and potential miRNAs were explored using MEME and the psRNATarget database. Hub genes crucial to thebaine biosynthesis were identified, contributing to essential cellular functions like growth, development, stress response, and signal transduction. Metabolic processes emerged as pivotal for thebaine production, indicating a broader role for the thebaine pathway gene network beyond primary metabolite production. Cell component subnetwork genes demonstrated associations with anatomical units, indicating involvement in plant defense responses. Dominant molecular functions drove plant defense responses. KEGG pathway analysis highlighted the significance of metabolic pathways and biosynthesis of secondary metabolites. Cluster analysis emphasized the relevance of the biosynthesis of amino acids, confirming the link between primary and secondary metabolites. Promoter analysis suggested the potential involvement of signal transduction in thebaine production. Hub genes were targeted by 40 miRNAs, suggesting potential novel biomarkers or target genes within the thebaine biosynthesis pathway. Based on the role of miRNAs identified in connection with the hub genes of the thebaine production process, the secondary metabolite pathway of thebaine appears to be associated with several key plant pathways, e.g. growth, development and stress response. However, these findings, based on bioinformatics analysis, warrant further experimental validation and promise to advance our understanding of the biosynthesis of thebaine and its interactions with other genes and metabolic pathways that influence the production of metabolites.

The goal of this study was to clarify the role of capsule size and morphology in the alkaloid yield of poppy. In 2023, two industrial varieties from large-scale cultivation were investigated. Three classes of capsule size (large, medium, and small) and four organelles (wall, placenta, disc, and thalamus) of the seedless capsule were studied for their mass proportions and alkaloid contents. In 'Meara', large capsules had 41% lower total alkaloid levels than smaller ones. In 'Morgana', there was no difference in total alkaloids between size groups, but large capsules had higher contents of codeine and thebaine. Among the four organelles, the wall represented the largest mass in both varieties (60–67%), while the disc and the thalamus gave the lowest proportions (below 9%). In the variety 'Meara', the highest alkaloid contents appeared in the wall (2.69% d.w.), followed by the placenta, and the other two parts. 'Morgana' accumulated the highest alkaloid content (3.72% d.w.) in the placenta. Morphine follows the trend of the total content, while codeine and thebaine may differ. Accurate information on the accumulation of alkaloids in the generative organs may contribute to increasing effectiveness in target-oriented breeding and optimization of cultivation with an appropriate choice of variety. [ABSTRACT FROM AUTHOR]

This paper discusses the development of rapid, reliable, and accurate polymerase chain reaction (PCR) assays for detecting opium poppy (Papaver somniferum L.) in food. Endpoint, quantitative, and digital PCRs were compared based on the amplification of a newly developed DNA marker targeting the NADPH-dependent codeinone reductase (COR) gene. Designed assays were shown to be highly specific and sensitive in discriminating opium poppy from other plant species, even in heat-treated and food samples. Digital PCR was the most sensitive, with a detection limit of up to 5 copies, i.e., approximately 14 pg of target DNA per reaction. Quantitative and digital PCR further allowed the quantification of opium poppy in up to 1.5 ng and 42 pg (15 copies) of target DNA in a sample, respectively. In addition, two duplex PCRs have been developed for the simultaneous detection of opium poppy DNA and representatives of (i) the Papaveraceae family or (ii) the Plantae kingdom. Finally, all designed assays were successfully applied for analysis of 15 commercial foodstuffs; two were suspected of being adulterated. The study results have an important impact on addressing food fraud and ensuring the safety and authenticity of food products. Beyond food adulteration, the study may also have significant implications for forensics and law enforcement. [ABSTRACT FROM AUTHOR]

This innovative study introduces the application of a 5% (v/v) poppy seed phenolic extract‐infused edible chitosan coating on fresh‐cut fruit salads (comprising apple, pineapple, pomegranate, and kiwi) stored at +4°C for 12 days. Non‐coated samples experienced notable changes: 4.30% weight loss, 25% decay, pH level at 3.59, titratable acidity of 0.18%, and browning index of 1.71. In contrast, fruit salads coated with chitosan–poppy seed phenolic extract exhibited significant improvements: weight loss reduced to 3.10%, decay limited to 3.13%, pH increased to 3.76, titratable acidity enhanced to 0.20%, and browning index notably decreased to 0.33. Soluble solids ranged from 11.83 to 14.71, L* from −8.13 to 18.64, a* from −1.85 to 22.35, and b* from 8.26 to 27.89 in non‐coated salads. Adding poppy seed phenolic extract to the coated fruits slightly expanded these ranges. Sensory evaluations consistently rated non‐coated samples between 1 and 3, while the coated samples received higher ratings between 6 and 7. These assessments consistently highlighted enhanced attributes, including intensified aroma, enriched color, improved taste, texture, and overall acceptability. Moreover, incorporating poppy seed phenolic extract amplified sensory qualities and significantly improved microbial safety (<106 CFU/g). In summary, the chitosan‐based coating, enriched with poppy seed phenolic extract, effectively extended the shelf life of fresh‐cut fruit salads. This integrated approach preserves key attributes, ensures microbial quality, and enhances the sensory characteristics of these products. The study's results emphasize its potential as a pivotal innovation in food preservation by providing specific and tangible outcomes. [ABSTRACT FROM AUTHOR]

Benzylisoquinoline alkaloids (BIAs) produced in opium poppy have been evidenced to heal patients suffering from various diseases. They, therefore, hold an integral position in the herbal drug industry. Despite the adoption of several approaches for the large-scale production of BIAs, opium poppy remains the only platform in this purpose. The only disadvantage associated with producing BIAs in the plant is their small quantity. Thus, recruiting strategies that boost their levels is deemed necessary. All the methods which have been employed so far are just able to enhance a maximum of two BIAs. Thus, if these methods are utilized, a sizable amount of time and budget must be spent on the synthesis of all BIAs. Hence, the exploitation of strategies which increase the content of all BIAs at the same time is more commercially effective and timesaving, avoiding the laborious step of resolving the biosynthetic pathway of each compound. Exposure to biotic and abiotic elicitors, development of a synthetic auto-tetraploid, overexpression of a WRKY transcription factor, formation of an artificial metabolon, and suppression of a gene in the shikimate pathway and miRNA are strategies that turn opium poppy into a versatile bioreactor for the concurrent and massive production of BIAs. The last three strategies have never been applied for BIA biosynthetic pathways. [ABSTRACT FROM AUTHOR]

Total morphine is an important urinary marker of heroin use but can also be present from prescriptions or poppy seed ingestion. In specimens with morphine concentrations consistent with poppy seed ingestion (<4,000 ng/mL), 6-acetylmorphine has served as an important marker of illicit drug use. However, as illicit fentanyl has become increasingly prevalent as a contaminant in the drug supply, fentanyl might be an alternative marker of illicit opioid use instead of or in combination with 6-acetylmorphine. The aim of this study was to quantify opiates, 6-acetylmorphine, fentanyl and fentanyl analogs in 504 morphine-positive (immunoassay 2,000 ng/mL cutoff) urine specimens from workplace drug testing. Almost half (43%) of morphine-positive specimens had morphine concentrations below 4,000 ng/mL, illustrating the need for markers to differentiate illicit drug use. In these specimens, fentanyl (22% co-positivity) was more prevalent than 6-acetylmorphine (12%). Co-positivity of 6-acetylmorphine and semi-synthetic opioids increased with morphine concentration, while fentanyl prevalence did not. In 110 fentanyl-positive specimens, the median norfentanyl concentration (1,520 ng/mL) was 9.6× higher than the median fentanyl concentration (159 ng/mL), illustrating the possibility of using norfentanyl as a urinary marker of fentanyl use. The only fentanyl analog identified was para-fluorofentanyl (n  = 50), with results from most specimens consistent with para-fluorofentanyl contamination in illicit fentanyl. The results confirm the use of fentanyl by employees subject to workplace drug testing and highlight the potential of fentanyl and/or norfentanyl as important markers of illicit drug use. [ABSTRACT FROM AUTHOR]

Medicinal and aromatic plants contribute to both the national economy and the well- being of forest villagers. In addition, these plants are generally used in a variety of industries such as medicine, food, paint, and perfumery. It is gaining popularity, and individuals are turning to herbal therapy as an alternative medical treatment. These medicinal plants can be popularised and utilised to boost the economies of medicinal-growing countries and provide livelihoods for local stakeholders. Furthermore, overexploitation of these therapeutic plants should be restricted, important species with high marketing potential should be protected, and cultivation of these plants should be encouraged for future use. Against this background, this study employs a hybrid multi-criteria decision-making technique to identify the medicinal and aromatic plants that contribute the most to the Turkish economy. The medicinal and aromatic plants that contributed the most to the country’s economy were found to be poppy seed, thyme, and laurel leaves. Moreover, the seed (sesame seed, flax seed, safflower seed) plants are determined as the least contributing medicinal and aromatic plants to the country’s economy. Cumin, anise, and salvia have also potential in terms of economics. Hence, these findings can help the farmers and decision-makers to determine which plants are more economically beneficial. Thus, plants with high economic value can be cultivated and exported to the rest of the world. [ABSTRACT FROM AUTHOR]

This article compares the performance of artificial intelligence (AI)-generated content and human-created content on social media platforms in the field of immunology and allergology. The study analyzed metrics such as "Accounts Reached," "Impressions," "Accounts Engaged," and "Likes" for posts created by a professional graphic designer and AI. The results showed a progressive decrease in engagement metrics over time for both types of posts, indicating a general decline in social media engagement. The study emphasizes the importance of human-AI collaboration to maximize AI's potential in content creation. [Extracted from the article]

A study published in the Journal of Analytical Toxicology has found that consuming seasoning containing poppy seeds can lead to positive urine drug test results for codeine. Previous guidelines that suggested codeine concentrations exceeding 300 ng/mL with a morphine to codeine ratio of less than 2 ruled out poppy seed consumption, but this study refutes those guidelines. The study involved four volunteers who consumed toast sprinkled with a poppy seed-containing seasoning blend, and urine samples collected after consumption showed positive results for codeine and morphine. The study highlights the need for caution when interpreting urine drug test results in the context of poppy seed consumption. The military has also addressed this issue and advised service members to avoid all poppy seed consumption. [Extracted from the article]

The Ranunculales are a hyperdiverse lineage in many aspects of their phenotype, including growth habit, floral and leaf morphology, reproductive mode, and specialized metabolism. Many Ranunculales species, such as opium poppy and goldenseal, have a high medicinal value. In addition, the order includes a large number of commercially important ornamental plants, such as columbines and larkspurs. The phylogenetic position of the order with respect to monocots and core eudicots and the diversity within this lineage make the Ranunculales an excellent group for studying evolutionary processes by comparative studies. Lately, the phylogeny of Ranunculales was revised, and genetic and genomic resources were developed for many species, allowing comparative analyses at the molecular scale. Here, we review the literature on the resources for genetic manipulation and genome sequencing, the recent phylogeny reconstruction of this order, and its fossil record. Further, we explain their habitat range and delve into the diversity in their floral morphology, focusing on perianth organ identity, floral symmetry, occurrences of spurs and nectaries, sexual and pollination systems, and fruit and dehiscence types. The Ranunculales order offers a wealth of opportunities for scientific exploration across various disciplines and scales, to gain novel insights into plant biology for researchers and plant enthusiasts alike. [ABSTRACT FROM AUTHOR]

The current study aims to investigate the tissue lesions induced by Poppy anemone in pregnant mice. The administration of Poppy anemone (200,400 and 600 mg/kg) begins from days 7-8 of pregnancy. The results showed an increase in the rate of deaths and miscarriages in pregnant female mice with an increase in the concentration used. The uterine horns also showed a difference in the distribution of embryos, the appearance of bleeding cases and the accumulation of fatty materials. Some absorbed embryos also appeared. As for histological changes in the skin of the fetuses, there was edema around the hair follicles and between the collagenous fibers of the dermis layer and around the skin, sweat, and sebaceous glands, presence of edema between the epidermis layer and the dermis, congestion of capillaries, the divergence of collagen fibers in the dermis of the skin, hyperkeratosis of the epidermis, presence of hydrophilic degeneration in the spiny cell layer of the epidermis, rarefaction of the white fibers of the dermis and congestion of blood capillaries. [ABSTRACT FROM AUTHOR]

There are few theories and little empirical evidence about the bilateral impact of substance use and coronavirus disease 2019 (COVID-19), so a logical and accurate picture of this area is required. We investigated the effects of opium use on severity of disease on hospitalized COVID-19 patients in east of Iran. Demographic and clinical characteristics, vital signs, laboratory tests, mortality rate, type and duration of opium consumption in hospitalized patients who recovered from COVID-19 in the follow-up after 3 months were evaluated. In this study, 60 (20%) participants were the opium user and 251 (80%) were the non-user patients. Based on clinical symptoms, hypertension and systolic blood pressure in opium user were significantly higher than non-user patients (p < 0.05). In the laboratory tests, only the level of urea was higher in the opium positive group (37 [26.5–48.5] vs. 32 [23–43], respectively) and the percent of lymphocytes were lower in the opium positive (17 [8.2–25.8] vs. 18.7 [13.85–26.35], respectively). The initial therapies of both opium positive and negative infected patients showed not any significant changes (p > 0.05). Among the studied groups, one deceased case with COVID-19 was related to a drug user patient. Although, uses of opium reduced the levels of some risk factors, vital signs at admission and initial therapies during hospitalization in COVID-19 patients but it increased lung and heart diseases. Also, the severity of COVID-19 including hospitalization and mortality were associated with opium consumption. [ABSTRACT FROM AUTHOR]

Noscapine is a naturally occurring alkaloid isolated from Papaver somniferum, commonly known as opium poppy or bread seed poppy. It edges over other opioids as it lacks addictive, sedative or euphoric effects. This review chronicles the saga of endeavours with noscapine, from modest efforts in the mid-1950s to its present anticancer potential and futuristic hope in combating COVID-19. We comprehensively searched for publications including noscapine- and noscapinoid-relevant keywords in different electronic databases such as PubMed, Google Scholars, Elsevier, Springer Link and Science Direct up to June 2023. We excluded those in a language other than English. Noscapine has long been used as an antitussive and suppresses coughing by reducing the activity of the cough centre in the brain. A great number of water-soluble noscapine analogues have been found to be impressive microtubule-interfering agents with a superior antiproliferative activity, inhibiting the proliferation of cancer cell lines with more potency than noscapine and bromo-noscapine. With enhanced drug delivery systems, noscapine has exerted significant therapeutic efficacy in animal models of Parkinson's disease, polycystic ovary syndrome, multiple sclerosis and other disorders. Furthermore, the merit of noscapine in crossing the blood–brain barrier makes it a putative candidate agent against neurodegenerative and psychiatric diseases. Its long safety record, widespread availability and ease of administration make it an ideal candidate for fighting several life-threatening conditions. Recent promising docking studies onnoscapine with main protease (Mpro) of SARS-CoV-2 paves the way for combinatorial drug therapy with anti-viral drugs and is hopeful in fighting and triumphing over any future COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the effects of different extraction methods on the oxidative stability and thermal stability of poppy seed oils obtained by using various extraction techniques. For this purpose, supercritical extraction and cold- and hot-pressing methods were employed, and the fatty acid composition, Fourier-transform infrared (FTIR) analysis, and thermal behaviors of the poppyseed oils were determined. Kinetic and thermodynamic parameters (activation energy, enthalpy, entropy, and Gibbs free energy values) were determined by using the Rancimat method at four different temperatures (110 °C, 120 °C, 130 °C, and 140 °C) in order to reveal the effects of environmental factors such as temperature on the oxidative stability of the poppyseed oils analyzed. As a result, the activation energy values calculated through Arrhenius-type plots ranged between 85.95 and 103.56 kJ mol−1, enthalpy values between 82.86 and 100.17 kJ mol−1, and entropy values between − 2.80 and − 41.23 kJ mol−1. Unlike other extraction methods, the spectrum was detected at 1713 cm−1 in poppyseed oil obtained by using the hot-pressing method. Different extraction methods significantly altered the fatty acid composition and oxidative stability of the oils. In conclusion, even though the heat treatment applied during the extraction process increases oil yield, it negatively affects oil quality. [ABSTRACT FROM AUTHOR]

The opium poppy (Papaver somniferum) is a global commercial crop that has been historically valued for both medicinal and culinary purposes. Naturally occurring opium alkaloids including morphine, codeine, thebaine, noscapine, and papaverine are found primarily in the latex produced by the plant. If the plant is allowed to fully mature, poppy seeds that do not contain the opium alkaloids will form within the pods and may be used in the food industry. It is possible for the seeds to become contaminated with alkaloids by the latex during harvesting, posing a potential health risk for consumers. In the USA, there have been more than 600 reported adverse events including 19 fatalities that may be linked to the consumption of a contaminated poppy-containing product such as home-brewed poppy seed tea. Unwashed poppy seeds and pods may be purchased over the Internet and shipped worldwide. The Forensic Chemistry Center, US Food and Drug Administration (FDA) has evaluated several mass spectrometers (MS) capable of rapid screening to be used for high-throughput analysis of samples such as poppy seeds. These include a direct analysis in real-time (DART) ambient ionization source coupled to a single-quadrupole MS, an atmospheric solids analysis probe (ASAP) ionization source coupled to the same MS, and ion mobility spectrometers (IMS). These instruments have been used to analyze 17 poppy seed samples for the presence of alkaloids, and the results were compared to data obtained using liquid chromatography with mass spectral detection (LC–MS/MS). Results from the 17 poppy seed samples indicate that the DART-MS, ASAP-MS, and IMS devices detect many of the same alkaloids confirmed during the LC–MS/MS analyses, although both the false-positive and false-negative rates are higher, possibly due to the non-homogeneity of the samples and the lack of chromatographic separation. [ABSTRACT FROM AUTHOR]

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REPI is a pivotal point enzyme in plant benzylisoquinoline alkaloid metabolism as it promotes the evolution of the biosynthetic branch of morphinan alkaloids. Experimental studies of its activity led to the identification of two modules (DRS and DRR) that catalyze two sequential steps of the epimerization of (S)- to (R)-reticuline. Recently, special attention has been paid to its genetic characterization and evolutionary history, but no structural analyses of the REPI protein have been conducted to date. We present here a computational structural characterization of REPI with heme and NADP cofactors in the apo state and in three complexes with substrate (S)-reticuline in DRS and intermediate 1,2-dehydroreticuline in DRS and in DRR. Since no experimental structure exists for REPI, we used its AlphaFold model as a scaffold to build up these four systems, which were submitted to all-atom molecular dynamics (MD) simulations. A comparison of MD results for the four systems revealed key dynamic changes associated with cofactor and ligand binding and provided a dynamic picture of the evolution of their structures and interactions. We also explored the possible dynamic occurrence of tunnels and electrostatic highways potentially involved in alternative mechanisms for channeling the intermediate from DRS to DRR. [ABSTRACT FROM AUTHOR]

We examined the proteomic profiles of three registered opium poppy cultivars (Papaver somniferum L.) with varying alkaloid contents. The study was conducted on both the stem and capsule organs. A high number of differentially expressed proteins (DEPs) were identified between the cultivars and the organs. We analyzed DEPs for their contribution in GO terms and KEGG pathways. The upregulated DEPs were significantly enriched in photosynthesis and translation for morphine-rich and noscapine-rich cultivars, respectively. The data indicated that photosynthesis is crucial for benzylisoquinoline alkaloid (BIA) biosynthesis, but different processes are also effective in morphine and noscapine biosynthesis, which occur at different branches in the biosynthetic pathway. The proteomics profiles revealed that energy demand is more effective in morphine biosynthesis, while translational control plays a leading role in noscapine biosynthesis. This study represents the first report demonstrating organ-based and cultivar-based protein expression differences in mature poppy plants. [ABSTRACT FROM AUTHOR]

The study investigated the effects of supplementing broiler diets with poppy (Papaver somniferum L.) seed meal (PSM) on growth performance, nutrient digestibility, faecal microbiota, and blood profiles. A total of 250 unsexed 1 d old broilers were allocated to five distinct treatment groups. PSM was incorporated into the diets at varying levels: 0 % (PSM 0), 5 % (PSM 5), 10 % (PSM 10), 15 % (PSM 15), and 20 % (PSM 20). The findings indicated that growth performance, including weight gain, feed intake, and feed conversion ratio (FCR), was significantly improved (P<0.05) in the PSM 20 group compared to the control. However, carcass weight experienced a notable decrease (P<0.05) in the PSM 20 group. Regarding nutrient digestibility, PSM supplementation led to reduced crude protein digestibility. Nevertheless, apparent metabolizable energy and ash content were significantly enhanced (P<0.05) in the PSM 15 and PSM 20 groups. Notably, faecal microbiota also experienced substantial improvement (P<0.05) in the PSM 20 group. In conclusion, the study demonstrates that incorporating poppy seed meal at a rate of 20 % in broiler diets enhances growth performance, improves nutrient digestibility, and positively influences faecal microbiota composition. [ABSTRACT FROM AUTHOR]

Papaver somniferum L. is cultivated for its edible seeds and for the production of alkaloids. A serious problem in seed trade and processing is the intentional mixing of excellent food-quality seeds with non-food-grade-quality seeds. Tracking the correct or illegitimate handling of seeds requires an efficient method for discrimination and individualization of poppy varieties. As in human and animal forensics, DNA variable regions containing short tandem repeats (STRs) located either in non-coding DNA or in gene sequences (EST-STRs) are preferred markers for discrimination between genotypes. Primers designed for 10 poppy EST-STR loci not analyzed so far were tested for their discriminatory ability on a set of 23 related P. somniferum L. genotypes. Thirty-three EST-STR alleles were identified together. Their polymorphic information content (PIC) values were in the range of 0.175–0.649. The PI value varied in the range of 0.140–0.669, and the cumulative PI was 1.2 × 10−5. PIsibs values varied between 0.436 and 0.820 and the cumulative value was lower (5.0 × 10−3). All analyzed genotypes were distinguished mutually, each with its own unique EST-STR profile. These newly developed EST-STR markers more effectively discriminated P. somniferum L. genotypes, even those genotypes whose DNA profiles were previously identical. [ABSTRACT FROM AUTHOR]

The opium poppy, Papaver somniferum L., is a forensically important plant due to the medicinal and illegal uses for the milky latex stored in the pods. This latex contains the alkaloids morphine, codeine, and thebaine that are used for their analgesic properties and/or for synthesizing other opioids. However, these compounds are highly addictive and have caused a national opioid epidemic. Two other Papaver species, P. setigerum DC. and P. bracteatum Lindl., are also of forensic interest because they pose both forensic and legal issues. They are largely uncontrolled under the Controlled Substances Act, making these species a common defense strategy. Current morphological and chemical identification methods have been moderately successful but have drawbacks. There is also a lack of sequencing data available. Therefore, exploiting the genome using chloroplast DNA barcoding markers could help to accurately identify these species of interest when plant material is taken. This study screened and assessed the genetic variation both between species and within populations of P. somniferum in nine cpDNA barcode regions (ndhF-rpl32, petA-psbJ, rpl32-trnL, rps16-trnQ, trnE-trnT, trnH-psbA, trnL-trnF, rpl16 intron, and psbE-petL). Published reference genomes from the NCBI GenBank database were aligned and compared for an initial in silico screening. Additionally, ten P. somniferum seed samples from various vendors were sequenced and compared across samples and to published reference data at the various barcode regions of interest. This study showed that the regions trnH-psbA and petA-psbJ have promise for utility in individualization for both inter- and intra-species individualization of P. somniferum. [ABSTRACT FROM AUTHOR]

This study examined the urine and hair opiate profiles associated with the daily consumption of presumptive codeine-predominant poppy seed food products. Ten participants consumed one of five food products at breakfast for 10 consecutive days. Baseline urine and hair samples were collected on Day 1. The urine samples were collected 4, 8 and 12 h following poppy seed consumption on Days 1 and 10, and the first morning void urine samples were collected on Days 2–10. A second hair specimen was collected on Day 20 ± 2. Urine drug test results: Three of the food products were associated with opiate-negative urine drug test results at all time points at a 300 ng/mL cut-off. Two of the food products were associated with opiate-positive drug test results at all non-baseline time points at a 300 ng/mL cut-off. Of these, all samples (n  = 60) were codeine-positive, and 27 (45%) were morphine-positive. Codeine concentrations exceeded morphine concentrations in every sample and always by multiples. Thirty-nine of the 60 samples (65%) were codeine-positive at a 2,000 ng/mL cut-off, while none of these samples were morphine-positive at this cut-off. None of the 60 samples reached an opiate threshold of 15,000 ng/mL, although one participant produced a maximum codeine concentration of 13,161 ng/mL (13,854 ng/mg creatinine). There was no clear trend toward increasing urinary opiate concentrations over the course of the study. Hair drug test results: The hair samples of two participants produced quantifiable codeine (41 pg/mg and 51 pg/mg), but no sample reached a common reporting threshold of 200 pg/mg for codeine or morphine. [ABSTRACT FROM AUTHOR]

Benzylisoquinoline alkaloids (BIAs) produced in opium poppy have been evidenced to heal patients suffering from various diseases. They, therefore, hold an integral position in the herbal drug industry. Despite the adoption of several approaches for the large-scale production of BIAs, opium poppy remains the only platform in this purpose. The only disadvantage associated with producing BIAs in the plant is their small quantity. Thus, recruiting strategies that boost their levels is deemed necessary. All the methods which have been employed so far are just able to enhance a maximum of two BIAs. Thus, if these methods are utilized, a sizable amount of time and budget must be spent on the synthesis of all BIAs. Hence, the exploitation of strategies which increase the content of all BIAs at the same time is more commercially effective and time-saving, avoiding the laborious step of resolving the biosynthetic pathway of each compound. Exposure to biotic and abiotic elicitors, development of a synthetic auto-tetraploid, overexpression of a WRKY transcription factor, formation of an artificial metabolon, and suppression of a gene in the shikimate pathway and miRNA are strategies that turn opium poppy into a versatile bioreactor for the concurrent and massive production of BIAs. The last three strategies have never been applied for BIA biosynthetic pathways.

SUMMARY: Whole‐genome duplication (WGD) leads to the duplication of both coding and non‐coding sequences within an organism's genome, providing an abundant supply of genetic material that can drive evolution, ultimately contributing to plant adaptation and speciation. Although non‐coding sequences contain numerous regulatory elements, they have been understudied compared to coding sequences. In order to address this gap, we explored the evolutionary patterns of regulatory sequences, coding sequences and transcriptomes using conserved non‐coding elements (CNEs) as regulatory element proxies following the recent WGD event in opium poppy (Papaver somniferum). Our results showed similar evolutionary patterns in subgenomes of regulatory and coding sequences. Specifically, the biased or unbiased retention of coding sequences reflected the same pattern as retention levels in regulatory sequences. Further, the divergence of gene expression patterns mediated by regulatory element variations occurred at a more rapid pace than that of gene coding sequences. However, gene losses were purportedly dependent on relaxed selection pressure in coding sequences. Specifically, the rapid evolution of tissue‐specific benzylisoquinoline alkaloid production in P. somniferum was associated with regulatory element changes. The origin of a novel stem‐specific ACR, which utilized ancestral cis‐elements as templates, is likely to be linked to the evolutionary trajectory behind the transition of the PSMT1‐CYP719A21 cluster from high levels of expression solely in P. rhoeas root tissue to its elevated expression in P. somniferum stem tissue. Our findings demonstrate that rapid regulatory element evolution can contribute to the emergence of new phenotypes and provide valuable insights into the high evolvability of regulatory elements. Significance Statement: This study demonstrates that the rapid evolution of regulatory elements can drive the emergence of novel phenotypes in plants. Our investigation, in particular, revealed that the evolution of stem‐specific high‐expression patterns of BIAs genes in P. somniferum was linked to rapid changes in regulatory elements. [ABSTRACT FROM AUTHOR]

Proper management of within-field variability is crucial for maximizing crop yield, production outcomes and resource use efficiency and reducing environmental impacts. This study evaluated the agroeconomic and environmental feasibilities of site-specific nitrogen fertilization (SNF) in opium poppy (Papaver somniferum L.). On-line visible and near-infrared reflectance spectroscopy was used to estimate soil pH, organic carbon (OC), soil organic matter (SOM), P, K, Mg, Ca, Na, moisture content (MC), Ca:Mg and K:Mg for one field in Spain. Normalized difference vegetation indexes of the previous crop were retrieved from Sentine-2 images. Rasterization of soil and crop data layers created a spatially homogenous dataset followed by delineation of a management zone (MZ) map using a k-means cluster analysis. MZ clusters were ranked relying on the within-cluster soil fertility attributes. A strip experiment was conducted by creating parallel stripes distributed over the MZ map, over which two SNF treatments (i.e., SNF-Kings approach [KA] and SNF-Robin Hood approach [RHA]) were compared against the uniform rate N (URN) control treatment. In SNF-KA, the highest and lowest N dose was applied in the most and least fertile MZ, respectively, whereas the opposite approach was adopted in the SNF-RHA treatment. Yield and cost–benefit analyses provided both SNF treatments to produce more yield (KA = 2.72 and RHA = 2.74 t ha−1) than the URN (2.64 t ha−1) treatment, leading to increasing gross margins by EUR 91 ha−1 (SNF–KA) and EUR 88.5 ha−1 (SNF–RHA). While SNF-KA reduced N input by 66.54 kg N ha−1, SNF–RHA applied more N by 17.90 kg N ha−1 than URN. Additionally, SNF–RHA attempted to equalize yield responses to N across MZ classes, with a small increase in N input. This study, therefore, suggests adopting SNF–RHA for increasing yield and gross margin and accurate distribution of N according to per MZ N response. Future studies, however, should address the limitations of the current study by delineating MZ maps with the incorporation of additional soil information (e.g., mineral N and clay) for optimizing N doses as well as evaluating agroeconomic performance across multiple sites and years using a full-budget analysis. [ABSTRACT FROM AUTHOR]

Protein engineering provides a powerful base for the circumvention of challenges tied with characteristics accountable for enzyme functions. CYP82Y1 introduces a hydroxyl group (-OH) into C1 of N-methylcanadine as the substrate to yield 1-hydroxy-N-methylcanadine. This chemical process has been found to be the gateway to noscapine biosynthesis. Owning to the importance of CYP82Y1 in this biosynthetic pathway, it has been selected as a target for enzyme engineering. The insertion of tags to the N- and C-terminal of CYP82Y1 was assessed for their efficiencies for improvement of the physiological performances of CYP82Y1. Although these attempts achieved some positive results, further strategies are required to dramatically enhance the CYP82Y1 activity. Here methods that have been adopted to achieve a functionally improved CYP82Y1 will be reviewed. In addition, the possibility of recruitment of other techniques having not yet been implemented in CYP82Y1 engineering, including the substitution of the residues located in the substrate recognition site, formation of the synthetic fusion proteins, and construction of the artificial lipid-based scaffold will be discussed. Given the fact that the pace of noscapine synthesis is constrained by the CYP82Y1-catalyzing step, the methods proposed here are capable of accelerating the rate of reaction performed by CYP82Y1 through improving its properties, resulting in the enhancement of noscapine accumulation. [ABSTRACT FROM AUTHOR]

Partially defatted poppy seeds, a by-product of poppy oil cold pressing, could be an interesting dietary supplement for obesity management. The aim of this study was to compare the effects of dietary supplementation with a small amount of native or partially defatted poppy seeds on gastrointestinal function and lipid metabolism in rats fed a high-fat diet. The defatted poppy seeds had, among others, lower fat content and higher fibre and protein content than native poppy seeds. The rats fed with a high-fat diet were characterised by severe metabolic disorders, especially in the liver, and poppy seeds were unable to prevent them. However, depending on the seed form, dietary supplementation with poppy seeds differentially affected the microbial and endogenous lipid metabolism in rats. In the distal intestine, both dietary seed forms stimulated microbial acetate production, and the supplementation with partially defatted poppy seeds additionally inhibited isobutyrate and isovalerate formation, which indicates a reduction in putrefaction. Both dietary seed forms increased cholesterol accumulation in the liver. Only dietary supplementation with partially defatted poppy seeds attenuated visceral fat and hepatic triglyceride accumulations and lowered blood triglyceride concentrations, and at the transcriptional level, the inhibition of SREBP-1c, which upregulates genes responsible for de novo lipogenesis, was additionally observed in this organ. In conclusion, a low and regular consumption of partially defatted poppy seeds may be beneficial in managing obesity-related disorders. [ABSTRACT FROM AUTHOR]

The purpose of this work was to analyse the energy productivity and efficiency of agricultural enterprises growing poppy. The number of enterprises investigated in the study was determined from a stratified random sample of 87, the data is from 2019, and the study was conducted in Turkey. All inputs and outputs used in poppy production were obtained by multiplying energy equations with conversion coefficients in determining the energy use of the enterprises. Data Envelopment Analysis (DEA) method was employed to calculate the technical, pure-technical, and scale efficiency of poppyproducing enterprises. Poppy energy inputs consisted of the use of human labour, machinery, fertilizer, pesticides, seeds, water, and fuel. The poppy capsule yield per unit area was regarded as the energy output. In the end, 40.23% of the total energy input in poppy production consisted of direct and 59.77% indirect energy. Non-renewable energy consumption (88.70%) was found to be rather high in the research area. Therefore, the use of chemical fertilizers and fuels, which are non-renewable energy sources, must be lessened for poppy plant production. The energy efficiency was found to be 0.08 in poppy production. According to this result, the production systems of the enterprises producing poppy are sufficient and energy is used efficiently. The specific energy value in the enterprises was calculated as 11.95 MJ kg-1 and the Technical Efficiency (TE) was calculated as 0.683. Producers produce at the same level with 68.3% of their capital, and 31.7 % saving. [ABSTRACT FROM AUTHOR]

This study examines how the Taliban's opium poppy eradication edict and the westward shift in illicit fentanyl production from China to India potentiates an opioid squeeze on Pakistan from its east-west flanks, influencing Pakistan's opioid production, distribution and use. As opioid output sputters in Afghanistan, while Indian chemists increasingly normalise illicit fentanyl production in South Asia, opportunistic Pakistani chemists will be incentivised to supply synthetic opioids to high-demand international markets, just as Pakistani farmers supply opium and heroin to international clients. This convergence has ramifications for Pakistani law, drug enforcement and public health, as domestic production increases domestic access to synthetic opioids. The article conducts an empirical examination of current trends in South Asian opioid production, distribution and use, along with an exegesis of the legal and regulatory systems in Pakistan, Afghanistan and China. This study also details how the Pakistani government should respond to this challenge legislatively, foremost through blanket ban of fentanyl and its precursors. Pakistan can reduce domestic use through evidence-based treatment programmes, including discrete and confidential treatment administered by females to female users, opioid substitution therapy, safe needle exchange programmes, culturally sensitive drug awareness campaigns, and increased data collection to detect geographic hotspot locations of opioid use and overdoses. [ABSTRACT FROM AUTHOR]

Papaver somniferum is a medicinal plant of the Papaveraceae family that has traditionally been used for diet or its therapeutic value for thousands of years. Mainly, morphine and noscapine alkaloids exhibit anti-analgesic and anticancer effects. However, gene expression patterns and regulatory elements, such as transcription factors between different tissues, still need to be detected. In this study, comparative in silico transcriptome analyses were conducted to examine the tissue-specificity of the benzylisoquinoline alkaloids (BIAs) biosynthetic genes and transcription factors (TFs) between morphine and noscapine cultivars. Analysis showed that BIA biosynthetic genes are expressed in a different pattern between two varieties. Results showed that some members of plant-specific secondary metabolites related to TF families, such as MYB, MADS-box, bHLH, NAC, and WRKY, are differentially expressed between tissues and varieties. [ABSTRACT FROM AUTHOR]

Opioids are important analgesics, and their pharmaceutical application is increasing worldwide. Many opioids are based on benzylisoquinoline alkaloids (BIA) and are still industrially produced from Papaver somniferum (opium poppy). (S)-norlaudanosoline ((S)-NLS) is a complex BIA and an advanced intermediate for diverse pharmaceuticals. The efficient synthesis of this scaffold could pave the way for a plant-independent synthesis platform. Although a promising biocatalytic route to (S)-NLS using norcoclaurine synthase (NCS) and ω-transaminase (TAm) has already been explored, the cost-effectiveness of this process still needs much improvement. Therefore, we investigated whether the synthesis could also be performed using whole cells to avoid the use of (partially) purified enzymes. With an optimized mixing ratio of TAm- and NCS-containing cells in batch biotransformations, 50 mM substrate was converted within 3 h with more than 90% yield and a high enantiomeric excess of the product (95%). To further increase the space–time yield, the cells were immobilized to enable their retainment in fixed-bed reactors. A comparison of glass beads, Diaion HP-2MG and alginate revealed that the addition of Diaion during bacterial growth led to the most active immobilisates. To facilitate sustained production of (S)-NLS, a fixed-bed setup was constructed based on lithographically printed columns from biocompatible PRO-BLK 10 plastic. The continuous production at two scales (5 mL and 50 mL columns) revealed insufficient system stability originating from biocatalyst leaching and inactivation. Thus, while the use of whole cells in batch biotransformations represents an immediate process improvement, the transfer to flow catalysis needs further optimization. [ABSTRACT FROM AUTHOR]

The experiment was conducted with three replications. The data on agronomic traits were used to estimate the genetic variability parameters, heritability, coefficient analysis, genetic gain and genetic advance (GA) and the traits was totally consisted of based on 60 genotypes. Analysis of variance revealed significant differences for all the studied traits. Low to high phenotypic coefficient of variation (PCV) and genotypic coefficient of variation (GCV) were recorded. The highest PCV and GCV values were found particularly for lodging percent (189.93% and 181.50%), opium yield per plant (107.85% and 17.27%), thebaine (86.93% and 83.07%) and seed yield per plant (66.35% and 57.27%) respectively, whereas low GCV and PCV (8.97% and 8.82% respectively) manifested for plant height. The highest broad sense heritability value was observed for plant height (96%) followed by thebaine and papaverine (91%), while lowest heritability (0.025%) revealed only for opium yield per plant. In present study, low to moderate genetic advance were manifested and high heritability and genetic advance as percentage of mean (>50) and genetic gain was recorded for plant height, narcoteine, thebaine and papaverine, indicating predominance of additive gene action for these characters. The results of this study suggest existence of variability for seed yield and other agronomic traits in the present poppy genotypes, which should be exploited in future breeding. [ABSTRACT FROM AUTHOR]