A nano-preparation for preventing and treating pine wood nematode disease

Abstract

The application discloses a nano preparation for preventing and treating pine wood nematode disease. Compared with traditional preparations, the nano preparation significantly improves the stability of a pesticide active ingredient under ultraviolet light, effectively prolongs the effective period thereof, matches the pH response characteristics with an acidic microenvironment of an infection site of the pine wood nematode, realizes on-demand release of the pesticide, simultaneously enhances the permeability and conductivity of the preparation on a tree body, and is better in the prevention and treatment effect on the pine wood nematode disease, and is suitable for various operation modes. The nano preparation has good environmental adaptability and wide popularization prospect.

Description

Technical Field

[0001] This invention belongs to the field of pesticide formulation processing, specifically relating to a nano-formulation for the prevention and control of pine wilt disease. Background Technology

[0002] Pine wilt disease, one of the most devastating diseases in global forest ecosystems, is known as "pine cancer" due to its rapid spread, difficulty in control, and high tree mortality rate. Since the first case was discovered in Nanjing, Jiangsu Province, my country in 1982, it has spread rapidly, causing the death of over 100 million pine trees in my country and resulting in annual economic losses of billions of US dollars. Among existing control methods, abamectin, emamectin benzoate, fluopyram, and nitrofurazone have shown significant advantages in controlling pine wilt disease due to their rapid onset and high killing efficiency. However, these compounds suffer from technical bottlenecks such as easy photodegradation, short effective period (usually only 3-5 days), and low bioavailability in forests (less than 30%). Furthermore, traditional application methods easily cause environmental pollution and ecotoxicity, which seriously restricts their practical application effectiveness.

[0003] Pesticide encapsulation technology utilizes natural or synthetic polymers as capsule wall materials to encapsulate the active pesticide ingredient (i.e., the core), forming microcapsules with a particle size of micrometers. This allows for controlled, slow release of pesticides, reducing pesticide degradation caused by environmental factors and minimizing toxicity to non-target organisms. Therefore, to a certain extent, pesticide microcapsules reduce pesticide loss, improve pesticide utilization efficiency, and reduce pesticide pollution of the ecological environment. However, because traditional pesticide microcapsules have a micrometer-scale particle size, their penetration power is not very strong when sprayed by drones, resulting in poor efficacy against pine wilt disease.

[0004] In recent years, research on novel pesticide formulations based on nanotechnology for the control of pine wilt disease has gradually become an international hot topic. Especially in drone spraying scenarios, nanoencapsulated formulations, with their excellent physicochemical properties and environmental friendliness, have shown great application potential and promotional value, providing a new solution for the green control of major forestry pests and diseases.

[0005] The information disclosed in this background section is intended only to enhance the understanding of the overall background of the invention and should not be construed as an admission or in any way implying that the information constitutes prior art known to those skilled in the art. Summary of the Invention

[0006] The purpose of this invention is to provide a nano-formulation for the prevention and control of pine wilt disease. It uses economical and safe encapsulation materials to prepare stable, uniform, and controllable nano-pesticide capsules, which enhances the photostability of the active pesticide ingredients, prolongs the pesticide's residual effect, and increases the pesticide's permeability within the pine tree, thus addressing the shortcomings of existing pesticide formulations in the field of pine wilt disease control.

[0007] Specifically, the present invention provides a nano-formulation for preventing and treating pine wilt disease, comprising the following weight percentages of each component:

[0008] Pesticide active ingredient 2%~10%

[0009] Emulsifier 1%~10%

[0010] Capsule wall material 1%~5%

[0011] Solvent 5%~30%

[0012] Catalyst 0.1%~1%

[0013] Dispersant 2%~5%

[0014] Thickener 0.1%~2%

[0015] Antifreeze 0.1%~1%

[0016] Defoamer 0.1%~0.5%

[0017] Synergist 3%~5%

[0018] Water balance.

[0019] Preferably, the active pesticide ingredient is one or a combination of several of abamectin, emamectin benzoate, fluopyram, and nitrofurazone. More preferably, the active pesticide ingredient is one or a combination of several of fluopyram and nitrofurazone.

[0020] ,

[0021] Avermectin structural formula

[0022] ,

[0023] Structural formula of emamectin benzoate

[0024] ,

[0025] Fluopyram structural formula

[0026] ,

[0027] The structural formula of nitrobenzamide.

[0028] The beneficial effects of this invention:

[0029] 1. Regarding existing pesticides for controlling pine wilt disease, abamectin, emamectin benzoate, fluopyram, and nitrofurazone are known as highly effective nematicides, but all suffer from poor photostability and low utilization rates in forests. This invention utilizes nano-encapsulation to achieve controlled release of easily photodegradable pesticide active ingredients, providing photostability. While this nano-formulation ensures control efficacy, it avoids the need for increased dosages in practical applications, which could harm the environment and non-target organisms.

[0030] 2. This invention utilizes nano-formulations with pH-responsive properties to match the acidic microenvironment of the nematode infection site, achieving "on-demand release." The high permeability of the formulation enhances the control effect against pine wilt disease, enabling top-down application by drones to reach the bottom, thus achieving the goal of green and effective control of pine wilt disease.

[0031] 3. The nano-formulation of the present invention has uniform size, stable storage, and particle size that can be controlled within 50-500nm, enabling industrial production. The pesticide nano-formulation has good market prospects in terms of improving pesticide utilization, reducing environmental pollution during agricultural production, and lowering agricultural production costs. Detailed Implementation

[0032] The specific embodiments of the present invention will be described in detail below with reference to the appendix, but it should be understood that the scope of protection of the present invention is not limited to the specific embodiments.

[0033] Unless otherwise expressly stated, throughout the specification and claims, the term "comprising" or its variations such as "including" or "comprises" shall be understood to include the stated elements or components without excluding other elements or other components.

[0034] This invention first provides a nano-formulation for preventing and treating pine wilt disease, the weight percentage of each component of which is as follows:

[0035] Pesticide active ingredient 2%~10%

[0036] Emulsifier 1%~10%

[0037] Capsule wall material 1%~5%

[0038] Solvent 5%~30%

[0039] Catalyst 0.1%~1%

[0040] Dispersant 2%~5%

[0041] Thickener 0.1%~2%

[0042] Antifreeze 0.1%~1%

[0043] Defoamer 0.1%~0.5%

[0044] Synergist 3%~5%

[0045] Water balance.

[0046] Preferably, the pesticide active ingredient in the nano-formulation of the present invention is one or a combination of several of abamectin, emamectin benzoate, fluopyram, and nitrofurazone, with fluopyram and nitrofurazone being particularly preferred. Studies have found that different pesticide active ingredients may affect the performance of the product.

[0047] Preferably, the emulsifier component in the nano-formulation of the present invention is one or a combination of several of the following: castor oil polyoxyethylene ether, tristyrene-phenylphenol polyoxyethylene ether, alkylphenol polyoxyethylene ether, dodecylbenzenesulfonate amine salt, calcium dodecylbenzenesulfonate, fatty alcohol polyoxyethylene ether, alkylphenol polyoxyethylene ether phosphate, isopropylamine dodecylbenzenesulfonate, triphenylphenol polyoxyethylene ether phosphate amine salt, and sorbitan monolaurate polyoxyethylene ether. More preferably, it is a mixture of hydroxyl polyethylene oxide block copolymer, calcium dodecylbenzenesulfonate, and triphenylphenol polyoxyethylene ether phosphate amine salt. Particularly preferred is a mixture of hydroxyl polyethylene oxide block copolymer, calcium dodecylbenzenesulfonate, and triphenylphenol polyoxyethylene ether phosphate amine salt in a weight ratio of (0.5~2):(1~3):(0.5~2). Products with excellent performance are obtained within the preferred emulsifier and proportion range.

[0048] Preferably, the solvent component in the nano-formulation of the present invention is one or a combination of several of xylene, Rhodiasolv Green25, cyclohexanone, Rhodiasolv ADMA10, S-150 solvent oil, methyl oleate, cyclohexane, dichloromethane and ethyl acetate.

[0049] Preferably, the capsule wall material in the nano-formulation of the present invention is one or a combination of several of the following: ethyl cellulose, chitosan, pectin, polydopamine, zein, sodium carboxymethyl cellulose, diphenylmethane diisocyanate, polyethylene glycol, polyether-modified diphenylmethane diisocyanate, chitosan, diphenylmethane diisocyanate-modified chitosan, phenyl dimethyl diisocyanate, and isophorone diisocyanate.

[0050] Preferably, the dispersant in the nano-formulation of the present invention is one or a combination of several of the following: calcium lignosulfonate, tristyrylphenol polyoxyethylene ether phosphate, sodium lignosulfonate, naphthalene sulfonate formaldehyde condensate sulfonate, succinate sulfonate, and sodium polycarboxylate.

[0051] Preferably, the catalyst in the nano-formulation of the present invention is one or a combination of several of the following: triethylamine, 3-(dichloromethylsilyl)propyllaurate, dibutyltin dilaurate, N,N-dimethylbenzylamine, and tri(dodecyl)trithiophosphite.

[0052] Preferably, the thickener in the nano-formulation of the present invention is one or a combination of several of soluble starch, gum arabic, gelatin, carboxymethyl cellulose, xanthan gum, magnesium aluminum silicate, and chitosan.

[0053] Preferably, the antifreeze agent in the components of the nano-formulation of the present invention is one or a combination of several of ethylene glycol, diethylene glycol, propylene glycol, glycerol, ethylene glycol butyl ether and propylene glycol butyl ether.

[0054] Preferably, the defoamer in the components of the nano-formulation of the present invention is one or a combination of several of the following: castor oil, diethylhexanol, isooctyl alcohol, propylene oxide, polydimethylsiloxane, polysiloxane, and tributyl phosphate.

[0055] Preferably, the synergist in the components of the nano-formulation of the present invention is one or a combination of several of the following: sodium dioctyl sulfonate succinate, isooctyl alcohol polyoxyethylene polyoxypropylene ether, isodecanol polyoxyethylene ether, p-(1,1,3,3-tetramethylbutyl)phenyl-polyethylene glycol, and siloxane polyoxyethylene ether, with a preferred combination of sodium dioctyl sulfonate succinate and siloxane polyoxyethylene ether.

[0056] Preferably, the nanoparticle size of the nanoparticle formulation in the present invention is 50~500 nm.

[0057] In some of the preferred technical solutions described above, the performance of the nano-formulations of the present invention, such as permeability, pH responsiveness, and stability, etc., but not limited thereto, will be even better.

[0058] The present invention also provides an application of the nano-formulation described herein in the prevention and treatment of pine wilt disease.

[0059] Unless otherwise specified, the experimental methods used in the following examples are conventional methods.

[0060] Unless otherwise specified, all materials and reagents used in the following examples are commercially available.

[0061] Example 1: Preparation of Nanoparticles

[0062] The raw materials are formulated in the following proportions:

[0063] 3 g of nitrofurazone technical grade was dissolved in 5 g xylene and 10 g cyclohexanone. 2 g of hydroxyl polyethylene oxide block copolymer, 3 g of calcium dodecylbenzenesulfonate, and 2 g of triphenylphenol polyoxyethylene ether phosphate amine salt were added, and the mixture was stirred until homogeneous. Then, 1 g of polydopamine and 2 g of isophorone diisocyanate were added, and the mixture was stirred until homogeneous to obtain the oil phase. 1.5 g of sodium lignosulfonate was dispersed in deionized water to obtain the aqueous phase. 0.03 g of dibutyltin dilaurate was added to the oil phase at a shear rate of 12000 rpm, followed by a slow addition of the aqueous phase. The system was cured at 50°C and 300 rpm for 2 h. Then, 0.05 g of xanthan gum, 1 g of ethylene glycol, 0.03 g of polysiloxane, 1 g of sodium sulfonate dioctyl succinate, and 2 g of siloxane polyoxyethylene ether were added, and the mixture was cured for another 1 h to obtain a 3% nitrofurazone nano-formulation.

[0064] Example 2: Preparation of Nanoparticles

[0065] The preparation method is the same as in Example 1, except that the active pesticide ingredient used is fluopyram.

[0066] Example 3: Preparation of Nanoparticles

[0067] The preparation method is the same as in Example 1, except that the emulsifier used is 1g of hydroxyl polyethylene oxide block copolymer, 3g of calcium dodecylbenzenesulfonate and 2g of triphenylphenol polyoxyethylene ether phosphate amine salt.

[0068] Example 4: Preparation of Nanoparticles

[0069] The preparation method is the same as in Example 1, except that the emulsifier used is 0.5g of hydroxyl polyethylene oxide block copolymer, 1g of calcium dodecylbenzenesulfonate and 0.5g of triphenylphenol polyoxyethylene ether phosphate amine salt.

[0070] Example 5: Preparation of Nanoparticle Formulations

[0071] The preparation method is the same as in Example 1, except that the capsule wall material used is 1 g of polydopamine and 3 g of diphenylmethane diisocyanate.

[0072] Example 6: Preparation of Nanoparticles

[0073] The preparation method is the same as in Example 1, except that the capsule wall material used is 1 g of polydopamine and 2 g of diphenylmethane diisocyanate.

[0074] Comparative Example 1: Preparation of Nanoparticles

[0075] The preparation method is the same as in Example 1, except that the active pesticide ingredient used is abamectin.

[0076] Comparative Example 2: Preparation of Nanoparticles

[0077] The preparation method is the same as in Example 1, except that the active pesticide ingredient used is abamectin. The difference lies in the emulsifier used, which consists of 0.2 g of hydroxyl polyethylene oxide block copolymer, 0.4 g of calcium dodecylbenzenesulfonate, and 0.2 g of triphenylphenol polyoxyethylene ether phosphate amine salt.

[0078] Comparative Example 3: Preparation of Nanoparticle Formulation

[0079] The preparation method is the same as in Example 1, except that the emulsifier used is 4g of hydroxyl polyethylene oxide block copolymer, 6g of calcium dodecylbenzenesulfonate and 4g of triphenylphenol polyoxyethylene ether phosphate amine salt.

[0080] Comparative Example 4: Preparation of Nanoparticles

[0081] The preparation method is the same as in Example 1, except that the capsule wall material used is 4g of diphenylmethane diisocyanate.

[0082] Comparative Example 5: Preparation of Suspension

[0083] After screening the parameters, a suspending agent was prepared.

[0084] 3g of nitrofurazone technical grade, 5g of block polyether, 0.5g of xanthan gum, 1g of kaolin, 4g of ethylene glycol, 0.5g of magnesium aluminum silicate, 0.5g of organosilicon defoamer, and 85.5g of water were mixed evenly to obtain nitrofurazone suspension.

[0085] Comparative Example 6: Preparation of Nanoparticles

[0086] The preparation method is the same as in Example 1, except that the synergist used is 3g of sodium sulfonate dioctyl succinate.

[0087] Comparative Example 7: Preparation of Nanoparticles

[0088] The preparation method is the same as in Example 1, except that the synergist used is 3g of siloxane polyoxyethylene ether.

[0089] Test Example 1

[0090] 1. Particle size determination

[0091] The average particle size of the formulations prepared in each example and comparative example was measured using a Malvern laser particle size analyzer.

[0092] 2. Verification of pH-responsive release characteristics

[0093] The formulations prepared in each example and comparative example were transferred to glass vials containing 100 mL of a water / ethyl acetate mixture (50:50, v / v) at pH 4.5 and 7.4, respectively, and shaken thoroughly at 70 ± 10 rpm. At 48 h, 1 mL of dialysate was removed, and then 1 mL of ethyl acetate was added to the system. The response release ratio of the nanocapsules was determined using high-performance liquid chromatography (HPLC), calculated as follows:

[0094]

[0095] Among them, V e (1 mL) represents the sample volume recorded at different time intervals, C n V represents the concentration (mg / mL) of the pesticide active ingredient in the release medium at time n, V0 (50mL) represents the volume of the release solution, and M represents the concentration (mg / mL) of the pesticide active ingredient in the release medium. i This indicates the total amount of active pesticide ingredients loaded.

[0096] 3. Studies on photostability

[0097] The formulations prepared in each example and comparative example were placed in translucent quartz bottles and irradiated with 254 nm ultraviolet light at room temperature. Samples were collected after 12 hours, diluted with methanol, and quantitatively analyzed by high-performance liquid chromatography (HPLC). All experiments were repeated three times to ensure the reliability of the results.

[0098] 4. Permeability Performance Study

[0099] To investigate the permeation and transport behavior of the formulations prepared in each example and comparative example within pine trees, the following methods were employed:

[0100] Preparations with the same active ingredient concentration were sprayed onto the surface of pine needles on pine trees of the same diameter at breast height (DBH). Seven days after application, the bark was peeled off and the woody tissue of the roots was ground. 2g of sawdust was weighed, and 5mL of deionized water, 10mL of acetonitrile, and 3g of sodium chloride were added. The mixture was vortexed for 5 minutes and then centrifuged to extract the solution. Subsequently, 1mL of the supernatant was taken and mixed with 50mg of C... 18 The mixture was combined with 100 mg MgSO4 and centrifuged again in a 2 mL centrifuge tube to complete the purification process. Finally, the content of the active pesticide ingredient in the root was quantitatively analyzed by liquid chromatography-mass spectrometry (LC-MS).

[0101] The particle size, release rate (pH=7.4 and 4.5), photolysis rate, and root pesticide active ingredient content determination results of the embodiments and comparative examples of the present invention are shown in Table 1.

[0102] Table 1. Data on particle size, release rate (pH=7.4 and 4.5), photolysis rate, and root pesticide active ingredient content of the embodiments and comparative examples of the present invention.

[0103]

[0104] The experimental results above show that the particle sizes prepared in Examples 1-6 all reached the range of 50nm-500nm, exhibiting pH-responsive release characteristics and excellent resistance to photolysis and permeability. However, in Comparative Examples 1-3, although they also exhibited pH-responsive release characteristics and resistance to photolysis, their particle sizes all exceeded 1μm. Comparative Example 4 did not possess pH-responsive release characteristics. The suspending agent in Comparative Example 5 exposed to ultraviolet light did not possess resistance to photolysis. Comparative Examples 6 and 7 indicate that the permeability enhancement effect of using a single synergist was slightly worse than that of using two or more synergists.

[0105] Test Example 2

[0106] 1. Test Objective

[0107] Test efficacy against pine wilt disease

[0108] 2. Testing Methods

[0109] In Rushan City, Shandong Province, eight-year-old black pine trees transplanted from a nursery were selected as experimental materials to evaluate the control effect on pine wilt disease. A pine nematode suspension was diluted with deionized water to approximately 1000 nematodes / mL, and 4 mL was inoculated onto each tree. The procedure involved making a wound on a disc branch of the sample tree, dripping the nematode solution onto it, and then sealing the wound with sterile absorbent cotton and plastic wrap to maintain moisture and promote nematode invasion. All treatments were performed under dry, windless conditions.

[0110] Two days after inoculation, drones were used to spray the treatment groups with the pesticides from Examples 1, 3, 6, and 7 at a dose of 10 g ai / mu, while the blank control was sprayed with deionized water. Each treatment had 30 pine trees, and the experiment was repeated three times. The experiment lasted for six months, and the mortality rate of pine trees in each group was recorded. The control effect was calculated based on the mortality rate.

[0111] 3. Test results are shown in Table 2.

[0112] Table 2. Mortality data of pine trees after treatment in Examples 1, 3, 6, and 7.

[0113]

[0114] Note: The difference analysis was performed using the Tukey test at the p < 0.05 level. There were no significant differences in the treatment of the same letter, but there were significant differences in the treatment of different letters.

[0115] As can be seen from the above experimental results, Example 1 showed a significantly better effect than the comparative examples in controlling pine wilt disease. Compared with the micron-sized formulation used in Comparative Example 3, the nanoscale formulation constructed in Example 1 has a smaller particle size and stronger tissue penetration ability, which effectively promotes the diffusion and conduction of the agent in the tree, significantly improves the insecticidal effect, and is reflected in a significant reduction in pine tree mortality.

[0116] Furthermore, Example 1 used two or more adjuvants with synergistic effects, which significantly improved formulation permeability and bioavailability. In contrast, Comparative Examples 6 and 7 used single adjuvant systems, which, although possessing some permeability, showed significantly lower overall efficacy than the combined treatment. The composite synergistic strategy demonstrates clear advantages in enhancing the internal penetration of nanoparticles, increasing target tissue penetration, and improving control efficiency.

[0117] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technologies and solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A nano-formulation for preventing and treating pine wilt disease, characterized in that, The formulation contains the following components in weight percentage: Pesticide active ingredient 2%~10% Emulsifier 1%~10% Capsule wall material 1%~5% Solvent 5%~30% Catalyst 0.1%~1% Dispersant 2%~5% Thickener 0.1%~2% Antifreeze 0.1%~1% Defoamer 0.1%~0.5% Synergist 3%~5% Water balance.

2. The nano-formulation for controlling pine wilt disease according to claim 1, characterized in that, The pesticide active ingredients in the nano-formulation are one or a combination of several of abamectin, emamectin benzoate, fluopyram, and nitrofurazone.

3. The nano-formulation for controlling pine wilt disease according to claim 1, characterized in that, The emulsifier component in the nano-formulation is one or a combination of several of the following: castor oil polyoxyethylene ether, tristyrene phenol polyoxyethylene ether, alkylphenol polyoxyethylene ether, dodecylbenzene sulfonate amine salt, calcium dodecylbenzene sulfonate, fatty alcohol polyoxyethylene ether, alkylphenol polyoxyethylene ether phosphate, isopropylamine dodecylbenzene sulfonate, triphenylphenol polyoxyethylene ether phosphate amine salt, and sorbitol monolaurate polyoxyethylene ether. And / or, the solvent component in the nano-formulation is one or a combination of several of xylene, Rhodiasolv Green 25, cyclohexanone, Rhodiasolv ADMA10, S-150 solvent oil, methyl oleate, cyclohexane, dichloromethane and ethyl acetate; And / or, the capsule wall material in the components of the nano-formulation is one or a combination of several of the following: ethyl cellulose, chitosan, pectin, polydopamine, zein, sodium carboxymethyl cellulose, diphenylmethane diisocyanate, polyethylene glycol, polyether-modified diphenylmethane diisocyanate, chitosan, diphenylmethane diisocyanate-modified chitosan, phenyl dimethyl diisocyanate, and isophorone diisocyanate; And / or, the dispersant in the components of the nano-formulation is one or a combination of several of the following: calcium lignosulfonate, tristyrylphenol polyoxyethylene ether phosphate, sodium lignosulfonate, naphthalene sulfonate formaldehyde condensate sulfonate, succinate sulfonate, and sodium polycarboxylate.

4. The nano-formulation for controlling pine wilt disease according to claim 1, characterized in that, The catalyst in the nano-formulation is one or a combination of several of the following: triethylamine, 3-(dichloromethylsilyl)propyllaurate, dibutyltin dilaurate, N,N-dimethylbenzylamine, and tri(dodecyl)trithiophosphite.

5. The nano-formulation for controlling pine wilt disease according to claim 1, characterized in that, The thickener in the nano-formulation is one or a combination of several of the following: soluble starch, gum arabic, gelatin, carboxymethyl cellulose, xanthan gum, magnesium aluminum silicate, and chitosan.

6. The nano-formulation for controlling pine wilt disease according to claim 1, characterized in that, The antifreeze agent in the components of the nano-formulation is one or a combination of several of ethylene glycol, diethylene glycol, propylene glycol, glycerol, ethylene glycol butyl ether, and propylene glycol butyl ether.

7. The nano-formulation for controlling pine wilt disease according to claim 1, characterized in that, The defoaming agent in the components of the nano-formulation is one or a combination of several of the following: castor oil, diethylhexanol, isooctyl alcohol, propylene oxide, polydimethylsiloxane, polysiloxane, and tributyl phosphate.

8. The nano-formulation for controlling pine wilt disease according to claim 1, characterized in that, The synergist in the components of the nano-formulation is one or a combination of several of the following: sodium sulfonate dioctyl succinate, isooctanol polyoxyethylene polyoxypropylene ether, isodecanol polyoxyethylene ether, p-(1,1,3,3-tetramethylbutyl)phenyl-polyethylene glycol, and siloxane polyoxyethylene ether.

9. The nano-formulation for controlling pine wilt disease according to any one of claims 1-8, characterized in that, The nanoparticles in the nanoparticle formulation have a particle size of 50-500 nm.

10. The use of the nano-formulation according to any one of claims 1-9 in the prevention and control of pine wilt disease.

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