Eco-Oriented Formulation and Stabilization of Oil-Colloidal Biodelivery Systems Based on GC-MS/MS-Profiled Phytochemicals from Wild Tomato for Long-Term Retention and Penetration on Applied Surfaces for Effective Crop Protection.

Vegetable oils as hydrophobic reserves in oil dispersions (OD) provide a practical approach to halt bioactive degradation for user and environment-efficient pest management. Using biodegradable soybean oil (57%), castor oil ethoxylate (5%), calcium dodecyl benzenesulfonates as nonionic and an-ionic surfactants, bentonite (2%), and fumed silica as rheology modifiers, we created an oil-colloidal biodelivery sytem (30%) of tomato extract with homogenization. The quality-influencing parameters, such as particle size (4.5 µm), dispersibility (97%), viscosity (61 cps), and thermal stability (2 years), have been optimized in accordance with specifications. Vegetable oil was chosen for its improved bioactive stability, high smoke point (257 °C), coformulant compatibility, and as a green build-in-adjuvant by improving spreadability (20-30%), retention and penetration (20-40%). In in vitro testing, it efficiently controlled aphids with 90.5% mortalities and 68.7-71.2% under field-conditions without producing phytotoxicity. Wild tomato-derived phytochemicals can be a safe and efficient alternative to chemical pesticides when combined wisely with vegetable oils.

Protein Kinases as Potential Targets Contribute to the Development of Agrochemicals.

Using agrochemicals against pest insects, fungi, and weeds plays a major part in maintaining and improving crop yields, which helps to solve the issue of food security. Due to the limited targets and resistance of agrochemicals, protein kinases are regarded as attractive potential targets to develop new agrochemicals. Recently, a lot of investigations have shown the extension of agrochemicals by targeting protein kinases, implying an increasing concern for this kind of method. However, few people have summarized and discussed the targetability of protein kinases contributing to the development of agrochemicals. In this work, we introduce the research on protein kinases as potential targets used in crop protection and discuss the prospects of protein kinases in the field of agrochemical development. This study may not only provide guidance for the contribution of protein kinases to the development of agrochemicals but also help nonprofessionals such as students learn and understand the role of protein kinases quickly.

Natural Product-Based Crop Protection Compounds─Origins and Future Prospects.

The continuing need to protect food and fiber production to address the demands of an expanding global population requires new pest management tools for crop protection. Natural products (NPs) have been and continue to be a key source of inspiration for new active ingredients (AIs) for crop protection, accounting for 17% of all crop protection AIs. However, potentially 50% of all crop protection compounds have or could have a NP origin if NP synthetic equivalents (NPSEs, synthetic compounds discovered by other approaches but for which a NP model also happens to exist) are also considered. The real and hypothetical NPs have their greatest impact as insight for new classes of crop protection compounds. Among the different product areas, NPs have their largest influence on the discovery of new insecticides, while herbicides have been the least affected by mining NPs for new AIs. While plants have historically been the largest (60% of the total) source of NPs of AIs for crop protection, in the last 30 years, bacterial NPs have become the largest source (42% of the total) of new classes (first in class) of NP-inspired crop protection AIs. Interest in NPs for crop protection continues, an aspect that is highlighted by the notable rise in the numbers of publications and patents on this topic, especially in the last 20 years. The present analysis further illustrates the continuing interest and value in NPs as sources of and inspiration for new classes of crop protection compounds.

High Value-Added Application of Natural Plant Products in Crop Protection: Construction and Pesticidal Activities of Piperine-Type Ester Derivatives and Their Toxicology Study.

To discover new potential pesticide candidates, recently, structural modification of natural bioactive products has received much attention. In this work, a series of new piperine-type ester derivatives were regio- and stereoselectively synthesized based on a natural alkaloid piperine isolated from Piper nigrum. Their structures were characterized by IR, mp, 1H NMR (13C NMR), and high-resolution mass spectrometry (HRMS). Against Tetranychus cinnabarinus Boisduval (Acari: Tetranychidae), compounds 4e, 4f, 4u, and 4v displayed the most significant acaricidal activity with LC50 values of 0.155, 0.117, 0.177, and 0.164 mg/mL, respectively. Particularly, compound 4f showed >120-fold higher acaricidal activity than piperine (LC50: 14.198 mg/mL). Notably, the acaricidal activity of 4f was equivalent to that of the commercial acaricide spirodiclofen (LC50: 0.115 mg/mL). Additionally, against Eriosoma lanigerum Hausmann (Hemiptera: Aphididae), compounds 4w and 4b' showed 1.8-fold aphicidal activity of piperine. Furthermore, via the scanning electron microscope (SEM) imaging method, the obvious destruction of the construction of the cuticle layer of 4f-treated T. cinnabarinus was observed. Compound 4f could be further studied as a lead acaricidal agent.

Transforming the evaluation of agrochemicals.

The present agrochemical safety evaluation paradigm is long-standing and anchored in well-established testing and evaluation procedures. However, it does not meet the present-day challenges of rapidly growing populations, food insecurity, and pressures from climate change. To transform the current framework and apply modern evaluation strategies that better support sustainable agriculture, the Health and Environmental Sciences Institute (HESI) assembled a technical committee to reframe the safety evaluation of crop-protection products. The committee is composed of international experts from regulatory agencies, academia, industry and nongovernmental organizations. Their mission is to establish a framework that supports the development of fit-for-purpose agrochemical safety evaluation that is applicable to changing global, as well as local needs and regulatory decisions, and incorporates relevant evolving science. This will be accomplished through the integration of state-of-the-art scientific methods, technologies and data sources, to inform safety and risk decisions, and adapt them to evolving local and global needs. The project team will use a systems-thinking approach to develop the tools that will implement a problem formulation and exposure driven approach to create sustainable, safe and effective crop protection products, and reduce, replace and refine animal studies with fit-for-purpose assays. A new approach necessarily will integrate the most modern tools and latest advances in chemical testing methods to guarantee the robust human and environmental safety and risk assessment of agrochemicals. This article summarizes the challenges associated with the modernization of agrochemical safety evaluation, proposes a potential roadmap, and seeks input and engagement from the broader community to advance this effort. © 2022 Health and Environmental Sciences Institute (HESI). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Increasing crop field size does not consistently exacerbate insect pest problems.

Increasing diversity on farms can enhance many key ecosystem services to and from agriculture, and natural control of arthropod pests is often presumed to be among them. The expectation that increasing the size of monocultural crop plantings exacerbates the impact of pests is common throughout the agroecological literature. However, the theoretical basis for this expectation is uncertain; mechanistic mathematical models suggest instead that increasing field size can have positive, negative, neutral, or even nonlinear effects on arthropod pest densities. Here, we report a broad survey of crop field-size effects: across 14 pest species, 5 crops, and 20,000 field years of observations, we quantify the impact of field size on pest densities, pesticide applications, and crop yield. We find no evidence that larger fields cause consistently worse pest impacts. The most common outcome (9 of 14 species) was for pest severity to be independent of field size; larger fields resulted in less severe pest problems for four species, and only one species exhibited the expected trend of larger fields worsening pest severity. Importantly, pest responses to field size strongly correlated with their responses to the fraction of the surrounding landscape planted to the focal crop, suggesting that shared ecological processes produce parallel responses to crop simplification across spatial scales. We conclude that the idea that larger field sizes consistently disrupt natural pest control services is without foundation in either the theoretical or empirical record.

BioClay™ prolongs RNA interference-mediated crop protection against Botrytis cinerea.

One of the most promising tools for the control of fungal plant diseases is spray-induced gene silencing (SIGS). In SIGS, small interfering RNA (siRNA) or double-stranded RNA (dsRNA) targeting essential or virulence-related pathogen genes are exogenously applied to plants and postharvest products to trigger RNA interference (RNAi) of the targeted genes, inhibiting fungal growth and disease. However, SIGS is limited by the unstable nature of RNA under environmental conditions. The use of layered double hydroxide or clay particles as carriers to deliver biologically active dsRNA, a formulation termed BioClay™, can enhance RNA durability on plants, prolonging its activity against pathogens. Here, we demonstrate that dsRNA delivered as BioClay can prolong protection against Botrytis cinerea, a major plant fungal pathogen, on tomato leaves and fruit and on mature chickpea plants. BioClay increased the protection window from 1 to 3 weeks on tomato leaves and from 5 to 10 days on tomato fruits, when compared with naked dsRNA. In flowering chickpea plants, BioClay provided prolonged protection for up to 4 weeks, covering the critical period of poding, whereas naked dsRNA provided limited protection. This research represents a major step forward for the adoption of SIGS as an eco-friendly alternative to traditional fungicides.

BioClay: next-generation crop protection strategy.

Whitefly and the viruses they transmit pose a serious threat to crops globally. Recently, Jain et al. showed that BioClay-mediated double-stranded RNA (dsRNA) spray provides an eco-friendly approach to controlling whitefly. This 'transgene-free next-generation' insect-specific crop protection strategy may help to reduce the use of chemical pesticides for controlling whitefly.

Different bees as vectors for entomovectoring with enhanced pollination and crop protection control: current practices, use cases and critical view on transport.

Honeybees, bumblebees and other insects have been used commercially for pollination for many years, and microbial biocontrol agents have also been widely used in pest control. Pollinators and formulations of microbial pest-control agents are routinely transported internationally on a large scale. A novel approach has been developed to use bees as vectors of microbial agents by inoculating the surface of the pollinators using dispensers in modified hives. This innovation extends the market for these products and results in better yields. A successful entomovector system requires selecting the vector pollinator most appropriate for the crop and location, based on various criteria, in combination with a registered microbial agent. Currently, pollinators and microbial agents are packed separately and combined at the point of use. Local sourcing of the pollinator in the system reduces the need for long-distance shipping of these live insects and may improve efficiency due to local adaptation; however, it will delay use and benefits of the system until research at each site/country catches up with the work already conducted in a few countries. In the meantime, clear guidance for innovative systems employing live insects could support the promising increase in food production.

Depuis plusieurs années, les abeilles mellifères, les bourdons et d'autres insectes sont commercialisés à des fins de pollinisation, parallèlement à l'utilisation désormais largement répandue de micro-organismes pour la lutte biologique contre les nuisibles. Les pollinisateurs et diverses formulations d'agents microbiens destinés à la lutte contre les nuisibles font régulièrement l'objet de transports internationaux à grande échelle. Une approche innovante mise au point récemment consiste à utiliser les abeilles en tant que vecteurs d'agents microbiens, en inoculant ces derniers sur la surface du pollinisateur par le biais de diffuseurs disposés dans les ruches modifiées à cette fin. Cette innovation amplifie le marché de ces produits et se traduit par un meilleur rendement. La réussite d'un système d'entomovection passe par la sélection judicieuse du vecteur pollinisateur en fonction des cultures à protéger et du site, sur la base de plusieurs critères, et par son utilisation en association avec un agent antimicrobien autorisé. À l'heure actuelle, les pollinisateurs et les agents microbiens sont conditionnés séparément et leur assemblage est effectué sur le site même d'utilisation. L'approvisionnement local en pollinisateurs au sein du système réduit la nécessité de transporter ces insectes vivants sur de longues distances et pourrait améliorer l'efficacité du système au moyen d'adaptations locales ; néanmoins, cela retardera la mise en oeuvre du système et l'obtention de résultats bénéfiques, le temps que la recherche conduite dans les sites ou les pays utilisateurs atteigne le niveau des avancées déjà enregistrées dans un petit nombre d'autres pays. En attendant, des directives claires en faveur des systèmes innovants basés sur l'utilisation d'insectes vivants pourraient oeuvrer à l'appui d'une croissance prometteuse de la production alimentaire.

El uso comercial de abejas melíferas, abejorros y otros insectos con fines de polinización tiene ya muchos años. También está muy extendido el empleo de agentes microbianos de control biológico como método de lucha contra las plagas. El transporte internacional y a gran escala de polinizadores y de ciertas formulaciones de plaguicidas microbianos es algo muy habitual. Ahora se ha concebido un novedoso planteamiento en el que se utilizan ápidos como vectores de agentes microbianos. Para ello, se impregna de estos agentes la superficie del insecto polinizador empleando dispensadores en colmenas modificadas. Tal innovación amplía el mercado de estos productos y depara mejores cosechas. Para que un sistema entomovectorial sea eficaz es preciso seleccionar el vector polinizador que mejor encaje con el cultivo y las condiciones locales atendiendo a diversos criterios y combinarlo con un agente microbiano registrado. Actualmente, los polinizadores y los agentes microbianos se embalan por separado y se combinan solo en el punto de aplicación. El aprovisionamiento del polinizador del sistema a partir de fuentes locales hace menos necesarios los envíos a larga distancia de estos insectos vivos y puede ofrecer más eficacia gracias al mayor grado de adaptación del insecto a las condiciones locales. Sin embargo, ello retrasará el uso del sistema y la obtención de los consiguientes beneficios, pues habrá que esperar a que en cada lugar o país se haya llevado el procedimiento tan lejos como se ha hecho hasta ahora en unos pocos países. Mientras tanto, la existencia de claras pautas sobre estos innovadores sistemas en que se emplean insectos vivos podría traducirse en un prometedor aumento de la producción alimentaria.

The power of cross-indication testing: agrochemicals originally stemming from a different indication.

Cross-indication testing is the assaying of final compounds, but also their intermediates or side products, from one agrochemical indication against target species of other product lines. This approach has proven to be a highly successful source of lead compounds, which led to several important crop protection products. This review article describes, which herbicides came from fungicides and insecticides, how fungicides have been obtained from herbicide and insecticide leads and which insecticides have their roots in herbicide and fungicide chemistry. © 2022 Society of Chemical Industry.

Application of Molecular-Modeling, Scaffold-Hopping, and Bioisosteric Approaches to the Discovery of New Heterocyclic Picolinamides.

Macrocyclic natural products and their derivatives are a valuable source for biologically active crop protection products and have had significant impact on the development of conventional agrochemicals. However, they can be challenging starting points for lead-generation efforts because of their size, structural complexity, and developability. Using molecular modeling and electrostatic analysis, alternative bicyclic isosteres were identified as replacements for the antifungal nine-membered macrocycle UK-2A. By application of a structure-based conformational approach, a series of heterocyclic replacements were derivatized to deliver promising fungicidal activity and scaffold bioisosteres were further diversified to investigate structure-activity relationships.

Results of Ring-Testing of a Semifield Study Design to Investigate Potential Impacts of Crop Protection Products on Bumblebees (Hymenoptera, Apidae) and a Proposal of a Potential Test Design.

In Europe, the risk assessment for bees at the European Union or national level has always focussed on potential impacts on honeybees. During the revision of the European Food Safety Authority bee guidance it was explicitly stated that bumblebees and solitary bees should be considered as well and consequently concerns were raised regarding the representativeness of honeybees for these other bee species. These concerns originate from differences in size as well as differences in behavioral and life history traits of other bee species. In response to this concern, the non-Apis working group of the International Commission for Plant-Pollinator Relationships initiated a ring-test of a semifield tunnel study design using the bumblebee Bombus terrestris. Nine laboratories participated, validating and improving the proposed design over a 2-year period. The intention of the ring-test experiments was to develop and if possible, establish a test protocol to conduct more standardized semifield tests with bumblebees. In the present study, the results of the ring-tests are summarized and discussed to give recommendations for a promising experimental design. Environ Toxicol Chem 2022;41:2548-2564. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

RNAi as a Foliar Spray: Efficiency and Challenges to Field Applications.

RNA interference (RNAi) is a powerful tool that is being increasingly utilized for crop protection against viruses, fungal pathogens, and insect pests. The non-transgenic approach of spray-induced gene silencing (SIGS), which relies on spray application of double-stranded RNA (dsRNA) to induce RNAi, has come to prominence due to its safety and environmental benefits in addition to its wide host range and high target specificity. However, along with promising results in recent studies, several factors limiting SIGS RNAi efficiency have been recognized in insects and plants. While sprayed dsRNA on the plant surface can produce a robust RNAi response in some chewing insects, plant uptake and systemic movement of dsRNA is required for delivery to many other target organisms. For example, pests such as sucking insects require the presence of dsRNA in vascular tissues, while many fungal pathogens are predominately located in internal plant tissues. Investigating the mechanisms by which sprayed dsRNA enters and moves through plant tissues and understanding the barriers that may hinder this process are essential for developing efficient ways to deliver dsRNA into plant systems. In this review, we assess current knowledge of the plant foliar and cellular uptake of dsRNA molecules. We will also identify major barriers to uptake, including leaf morphological features as well as environmental factors, and address methods to overcome these barriers.

Metal nanoparticles against fungicide resistance: alternatives or partners?

Chemical control suffers from the loss of available conventional active ingredients due to strict environmental safety regulations which, combined with the loss of fungicide efficacy due to resistance development, constitute major problems of contemporary crop protection. Metal-containing nanoparticles (MNPs) appear to have all the credentials to be next-generation, eco-compatible fungicide alternatives and a valuable anti-resistance management tool. Could the introduction of MNPs as nano-fungicides be the answer to both reducing the environmental footprint of xenobiotics and dealing with fungicide resistance? The potential of MNPs to be utilized as nano-fungicides, both as alternatives to conventional fungicides or/and as partners in combating fungicide resistance, is discussed in terms of effectiveness, potential antimicrobial mechanisms as well as synergy profiles with conventional fungicides. However, their "golden" potential to be used both as alternatives and partners of conventional fungicides to combat resistance and reduce environmental pollution is challenged by undesirable effects towards non-target organisms such as phytotoxicity, toxicity to humans and environmental ecotoxicity, constituting risks that should be considered before their commercial introduction as nano-pesticides at a large scale. © 2022 Society of Chemical Industry.

Pesticide Informatics Platform (PIP): An International Platform for Pesticide Discovery, Residue, and Risk Evaluation.

Pesticides are widely used agrochemicals for crop protection. The need for novel pesticides becomes urgent as a result of the emergence of resistance and environmental toxicity. Pesticide informatics has been applied in different phase processes of pesticide target identification, active ingredient design, and impact evaluation. However, these valuable resources are scattered over the literature and web, limiting their availability. Here, we summarize and connect research on pesticide informatics resources. A pesticide informatics platform (PIP) was constructed to share these tools. We finally discuss the future direction of pesticide informatics, including pesticide contamination. We expect to share the pesticide informatics approaches and stimulate further research.

High Value-Added Application of Natural Plant Products in Crop Protection: Honokiol Monoester/Diester Derivatives Containing the Novel Core Scaffold of Benzodihydrofuran and Their Agricultural Bioactivities and Control Effects.

To discover new potential botanical insecticides from plant secondary metabolites, a series of new honokiol-type monoester/diester derivatives containing the core scaffold of benzodihydrofuran were synthesized by structural modification of honokiol. Against Mythimna separata Walker, 2-hydroxymethy-5-(2'-(para-chlorobenzoyloxy)-5'-(1″,2″-epoxypropanyl))phenyl-2,3-dihydrobenzofuran (5) and 2-(2″-chloropyridin-5″-ylcarbonyloxy)methylene-5-(2'-(2″-chloropyridin-5″-ylcarbonyloxy)-5'-(1″,2″-epoxypropanyl))phenyl-2,3-dihydrobenzofuran (37) displayed >2.1-fold promising insecticidal activity of the precursor honokiol. Against Aphis citricola Van der Goot, 2-hydroxymethy-5-(2'-(tridecylcarbonyloxy)-5'-(1″,2″-epoxypropanyl))phenyl-2,3-dihydrobenzofuran (21) (LD50: 0.049 µg/nymph) and 2-(para-fluorobenzylcarbonyloxy)methylene-5-(2'-(para-fluorobenzylcarbonyloxy)-5'-(1″,2″-epoxypropanyl))phenyl-2,3-dihydrobenzofuran (31) (LD50: 0.040 µg/nymph) showed 3.5- and 4.3-folds potent aphicidal activity of honokiol (LD50: 0.171 µg/nymph), respectively. Interestingly, 2-(tridecylcarbonyloxy)methylene-5-(2'-(tridecylcarbonyloxy)-5'-(1″,2″-epoxypropanyl))phenyl-2,3-dihydrobenzofuran (46) (LC50: 0.186 mg/mL) and 2-(dodecylcarbonyloxy)methylene-5-(2'-(dodecylcarbonyloxy)-5'-(1″,2″-epoxypropanyl))phenyl-2,3-dihydrobenzofuran (53) (LC50: 0.159 mg/mL: >6.4-fold of honokiol (LC50: 1.024 mg/mL)) exhibited promising acaricidal activity and control efficiency against Tetranychus cinnabarinus Boisduval. Structure-activity relationships indicated that a specific length of the aliphatic chain is necessary for the agricultural activities of honokiol monoester/diester derivatives, especially for the acaricidal activity of diester derivatives.

Importance of chemical polymorphism in modern crop protection.

The development of agrochemical products faces many scientific challenges. After selection of an agrochemical candidate its properties will have to be optimized to guarantee best bioavailability and stability under many different conditions in various formulation types. These challenges are influenced by the solid-state properties of the active ingredient and this makes the selection of an optimized solid-state form of modern agrochemicals at early development stages very valuable. The increasing awareness of the solid state of agrochemicals is reflected in the importance of polymorphism patent applications, which may enhance the risk of litigations. This review aims to present strategies for the solid-form selection process of agrochemical development candidates. It introduces the different techniques for crystallization and analytics and demonstrates the influence of the solid state on different formulation types. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Trifluoromethylpyridine: An Important Active Fragment for the Discovery of New Pesticides.

Trifluoromethylpyridine (TFMP) is a biologically active fragment formed by connecting trifluoromethyl and pyridine ring. As a result of its unique physical and chemical properties and outstanding biological activity, a variety of pesticide compounds with the TFMP fragment have been discovered and marketed and have played important roles in crop protection research. It is therefore a timely and valuable task to summarize the rationality on how to create new molecules containing TFMP fragments based on the structure-activity relationships, design mentality, and potential mechanism. This review gives a brief summary on the pesticides containing TFMP fragments in the past 5 years and introduces the latest progress of our group in this field. The aim is to provide readers with a convenient route to touch this topic and hopefully serve some educational purpose for graduate students as well.

Exploring cellulose nanocrystals obtained from olive tree wastes as sustainable crop protection tool against bacterial diseases.

Nanomaterials in agriculture represent one of the most innovative method for protecting crops, due to possibility of being applied as nanopesticides or nanocarriers for active ingredients. Furthermore, nanotechnology could be combined with the concept of circular economy through the opportunity of obtaining highly technological nanometric materials starting from agro-industrial wastes. The present research evaluated the possibility of synthesizing cellulose nanocrystals (CNCs) from olive pruning wastes through chemical bleaching, reusing them as sustainable tool to control the causal agent of the olive knot disease (Pseudomonas savastanoi pv. savastanoi). CNCs showed an interesting in vitro effect in inhibiting bacterial growth and bacterial biofilm formation, as well as the ability of reducing bacterial epiphytic survival in a comparable way to copper sulphate on leaf surfaces, when used at 1% w/v. CNCs were at the same time investigated for their interaction with olive tree seedlings, showing no negative effects on leaf development, and a promising root uptake, indicating that CNCs could be used also as nanocarriers for active ingredients. Obtained results highlight the innovative possibility of designing sustainable plant protection strategies capable of revalorise lignocellulosic wastes, meaning a simultaneous low environmental impact thanks to reduction of traditional agrochemicals input.