Modification Of Properties Research Articles

Excited‐State Dynamics and Optical Properties of Silica Under Ultrafast Laser Irradiation

AbstractExcited by intense infrared ultrafast light pulses, a wide bandgap material undergoes nonlinear ionization, generating a high density of free electrons in conduction states. As a result, the electronic band structure is critically modified and the bandgap shrinks. This induces rapid changes in optical properties, dramatically affecting the absorption spectrum during light coupling to the dielectric surface or during nonlinear propagation inside the bulk. This study analyzes the structural behavior and the modification of the optical properties of laser‐excited silica glass at the molecular cluster level through first‐principles simulations. Employing density functional theory and the GW approximations for band structure under nonequilibrium conditions, alongside the Bethe–Salpeter equation, the dynamics of the optical properties of fused silica are comprehensively explored. The behavior of excited fused silica in a wide photon energy range (from a few to 20 eV) is thus predicted. Laser‐induced electron excitation triggers a redistribution of charges between oxygen and silicon atoms, accompanied by a significant increase in electronic pressure, local atomic structure rearrangement, and material expansion. Molecular dynamics simulations offer a temporal perspective on the excited state dynamics, unveiling the intricate interplay between electronic and atomic effects on bandgap evolution. The analysis sheds light on excitonic resonances, intraband and interband transitions in fused silica under ultrafast laser irradiation, providing valuable insights into its excited state behavior and optical properties.

Rheological Property Modification of a Molten-State Polyamide through the Addition of an α-Olefin-Maleic Anhydride Copolymer.

The rheological properties of a polyamide (PA) resin with low crystallinity were modified by melt-mixing it with a small amount of an alternative α-olefin-maleic anhydride copolymer as a reactive compound. Because PA has a low melting point, rheological characterization was performed over a wide temperature range. Owing to the reaction between PA and the alternative α-olefin-maleic anhydride copolymer, the blend sample behaved as a long-chain branched polymer in the molten state. The thermo-rheological complexity was obvious owing to large flow activation energy values in the low modulus region, i.e., the rheological time-temperature superposition principle was not applicable. The primary normal stress difference under steady shear was greatly increased in the wide shear rate range, leading to a large swell ratio at the capillary extrusion. Furthermore, strain hardening in the transient elongational viscosity, which is responsible for favorable processability, was clear. Because this is a simple modification method, it will be widely employed to modify the rheological properties of various polyamide resins.

Evidence of oxygenated species in laser-irradiated carbon particles

Combustion-generated carbon nanoparticles exhibit a variety of optical and physicochemical properties. Therefore, when applying laser diagnostic tools for monitoring purpose, it is important to consider the different response of the particles with varying properties as well as the impact of laser irradiation on these properties. In this work, we analyze the possible modification of particle optical and physicochemical properties by coupling extinction measurements with FT-IR and Raman spectroscopy. The aim is to retrieve optical, chemical, and structural properties of the particles under analysis. To our knowledge, the approach proposed in this work has not yet been performed on irradiated particles. Particles are sampled from a premixed flame at two heights above the burner, representing two different aging stages. While extinction measurements are carried out in-flow, FT-IR and Raman spectroscopy are performed on particles collected for ex-situ analysis. Moreover, the analysis is conducted on both pristine and irradiated nanoparticles with one and ten laser shots. While nascent particles do not exhibit relevant modification under laser irradiation, heating mature particles with one or more laser pulses of relatively high energy density is observed to significantly affect absorption properties, particle structures and specific surface functionalities. The presence of oxygenated species in mature particles and in particular the structures spectroscopically correlated with graphene oxide indicates that specific chemical reaction pathways can occur under laser irradiation, likely promoted in the ambient condition under analysis.

Modification of functional and technological properties of protein products from peas by domestic bacterial proteases

Modification of functional and technological properties of protein products from peas by domestic bacterial proteases

Characterization of a Fatty Acid Amide Hydrolase (FAAH) in Hirudo Verbana

The endocannabinoid system plays a critical role in modulating both peripheral and central nervous system function. Despite being present throughout the animal kingdom, there has been relatively little investigation of the endocannabinoid system beyond traditional animal models. In this study, we report on the identification and characterization of a putative fatty acid amide hydrolase (FAAH) in the medicinal leech, Hirudo verbana. FAAH is the primary enzyme responsible for metabolizing the endocannabinoid signaling molecule arachidonoyl ethanolamide (anandamide or AEA) and therefore plays a critical role in regulating AEA levels in the nervous system. mRNA encoding Hirudo FAAH (HirFAAH) is expressed in the leech central nervous system (CNS) and sequence analysis suggests that this is an orthologue of FAAH-2 observed in vertebrates. Functionally, HirFAAH has serine hydrolase activity based on activity-based protein profiling (ABPP) studies using the fluorophosphonate probe TAMRA-FP. HirFAAH also hydrolyzes arachidonyl 7-amino, 4-methyl coumarin amide (AAMCA), a substrate specific to FAAH. Hydrolase activity during both the ABPP and AAMCA assays was eliminated by a mutation at a conserved catalytic serine. Activity was also blocked by the known FAAH inhibitor, URB597. Treatment of Hirudo ganglia with URB597 potentiated synapses made by the pressure-sensitive mechanosensory neuron (P cell), mimicking the effects of exogenously applied AEA. The Hirudo CNS has been a useful system in which to study properties of endocannabinoid modulation of nociception relevant to vertebrates. Therefore, this characterization of HirFAAH is an important contribution to comparative studies of the endocannabinoid system.

Abstract We110: Novel allosteric ligand designed to prevent Autoantibody targeting the Angiotensin Type 1 Receptor (AT1R) in cardiovascular diseases (CVD)

Background: The clinical data suggest an association of autoantibodies (AAb) targeting angiotensin II type1 receptor (AT1R) and outcomes in heart failure (HF) and preeclampsia. Notably, patient’s risk increases 2 to 4-fold for heart diseases and hypertension. Although AT1R blockers (ARBs) have emerged as a key component in the therapeutic arsenal against CVD, we believe that rather than completely blocking AT1R signaling, maintaining a balanced signaling is crucial for cardiovascular homeostasis. Therefore, we posit that reducing AT1R overactivation and blocking AAb-mediated activation could benefit cardiac health and attenuate the progression of CVD. In our previous study (PMID:36440576), we identified small molecules capable of inhibiting AAb-induced AT1R signaling. Leveraging these observations, we have developed a novel AT1R allosteric ligand that inhibits autoantibody binding to AT1R while still retaining normal AT1R signaling. Methods: Using computational and medicinal chemistry approaches, we designed a series of novel AT1R ligands and obtained compounds with >98% purity through chemical synthesis. Monoclonal antibodies mimicking AT1R-AAb have been generated. Serum samples from dilated cardiomyopathy (DCM) and preeclampsia (PE) patient cohorts were collected and presence of AT1R-AAb was determined using ELISA and epitope-peptide competition studies. Pharmacological characterization of compounds was performed using calcium mobilization, 125I -AngII binding, ex vivo vasoconstriction, and ELISA assays. Results: We identified an AT1R allosteric compound that reduced AngII-mediated calcium signaling with a 5-fold shift in EC 50 . The IC 50 was determined to be 18 µM. It reduces the AngII-mediated vasoconstriction while blocking both monoclonal and patient-derived autoantibody binding with an IC 50 of 5 µM. Conclusion: We have identified a novel AT1R allosteric ligand with negative allosteric modulator (NAM) properties, which has the potential to block autoantibodies and could serve as a new generation of ARBs. Uniquely, it retains beneficial AT1R signaling without competing with AngII, and its allosteric ligand property can be tailored to achieve optimal AT1R signaling.

Synthesis and biological studies of 2-aminothiophene derivatives as positive allosteric modulators of glucagon-like peptide 1 receptor

As a step toward the development of novel small-molecule positive allosteric modulators (PAMs) of glucagon-like peptide 1 receptor (GLP-1R) for the treatment of type 2 diabetes, obesity, and heart diseases, we discovered a novel 2-amino-thiophene (2-AT) based lead compound bearing an ethyl 3-carboxylate appendage. In this work, we report the syntheses and biological studies of more than forty 2-AT analogs, that have revealed a 2-aminothiophene-3-arylketone analogue 7 (MW 299) showing approximately a 2-fold increase in insulin secretion at 5 μM when combined with the GLP-1 peptide at 10 nM. In vivo studies using CD1 mice at a dose of 10 mg/kg, clearly demonstrated that the blood plasma glucose level was lowered by 50% after 60 min. Co-treatment of 7 with sitagliptin, an inhibitor of GLP-1 degrading enzyme Dipeptidyl Peptidase IV, further confirmed 7 to be an effective PAM of GLP-1R. The small molecular weight and demonstrated allosteric modulating properties of these compound series, show the potential of these scaffolds for future drug development.

Consequences of Spiraea tomentosa invasion in Uropodina mite (Acari: Mesostigmata) communities in wet meadows

Vegetation cover has been consistently reported to be a factor influencing soil biota. Massive spreading of invasive plants may transform native plant communities, changing the quality of habitats as a result of modification of soil properties, most often having a directional effect on soil microorganisms and soil fauna. One of the most numerous microarthropods in the litter and soil is Acari. It has been shown that invasive plants usually have a negative effect on mites. We hypothesized that invasive Spiraea tomentosa affects the structure of the Uropodina community and that the abundance and species richness of Uropodina are lower in stands monodominated by S. tomentosa than in wet meadows free of this alien species. The research was carried out in wet meadows, where permanent plots were established in an invaded and uninvaded area of each meadow, soil samples were collected, soil moisture was determined and the mites were extracted. We found that Uropodina mite communities differed in the abundance of individual species but that the abundance and richness of species in their communities were similar. S. tomentosa invasion led primarily to changes in the quality of Uropodina communities, due to an increase in the shares of species from forest and hygrophilous habitats. Our results suggest that alien plant invasion does not always induce directional changes in mite assemblages, and conclude that the impact of an alien species on Uropodina may cause significant changes in the abundance and richness of individual species without causing significant changes in the abundance and diversity of their community.

Rheological and sensory properties of chickpea and quinoa pastes and gels for plant-based product development.

The aim of this study was to investigate the modification of mechanical, rheological, and sensory properties of chickpea pastes and gels by incorporating other ingredients (olive oil or quinoa flour), to develop plant-based alternatives that meet consumer demands for healthy, natural, and enjoyable food products. The pastes and gels were made with different amounts of chickpea flour (9% and 12%, respectively). For each product, a first set of products with different oil content and a second set with quinoa flour (either added or replaced) were produced. The viscoelastic properties of the pastes and the mechanical properties of the gels were measured. Sensory evaluation and preference assessment were carried out with 100 participants using ranking tests. The study found remarkable differences in rheological, mechanical, and sensory properties of chickpea products upon the inclusion of oil and quinoa flour. The addition of oil increased the viscosity and decreased the elastic contribution to the viscoelasticity of the pastes, while it improved the firmness and plasticity in gels. It also increased the creaminess and preference of both pastes and gels. Replacing chickpea with quinoa flour resulted in less viscous pastes and gels with less firmness and more plasticity. In terms of sensory properties, the use of quinoa as a replacement ingredient resulted in less lumpiness in the chickpea paste and less consistency and more creaminess in both the pastes and gels, which had a positive effect on preference. The addition of quinoa increased the viscosity of pastes and the firmness and stiffness of gels. It increased the consistency and creaminess of both pastes and gels. Quinoa flour and/or olive oil are suitable ingredients in the formulation of chickpea-based products. They contribute to the structure of the system, providing different textural properties that improve acceptance.

Growth of thick amorphous carbon films on alumina for improved tribological properties

Alumina, as a pivotal ceramic material extensively utilized in contemporary applications, the surface modification and enhancement of tribological properties are crucial. In this study, reactive magnetron sputtering was employed to deposit Ti, Si co-doped hydrogen-free (TiSi/a-C), and hydrogenated amorphous carbon films (TiSi/a-C:H) with a thickness exceeding 7 μm onto the surface of alumina ceramic substrates. Utilizing the design of the film structure, the difficulty of film-substrate adhesion was resolved by controlling the deposition time to influence the growth rate of the film, thereby enabling the reliable fabrication of thick films. The adhesion of the TiSi/a-C film exhibits the highest value, with an Lc1 value of 36.7 N. The hardness of the TiSi/a-C:H reaches a maximum of 15.2 GPa, and the hardness is closely correlated with the reaction gas utilized during its depositional process. The wear rate of amorphous carbon film decreases by 34 times compared to alumina substrate. During the dissociation of CH4 at a high hydrogen-to-carbon ratio, more hydrogen atoms are involved in the chemical reaction. The introduction of hydrogen elevates the H/E and sp3/sp2 ratios within the film, thereby favoring the generation of low-friction surfaces and refining the tribological performance of alumina ceramics.

Inhaled Nanoparticulate Systems: Composition, Manufacture and Aerosol Delivery.

An increasing growth in nanotechnology is evident from the growing number of products approved in the past decade. Nanotechnology can be used in the effective treatment of several pulmonary diseases by developing therapies that are delivered in a targeted manner to select lung regions based on the disease state. Acute or chronic pulmonary disorders can benefit from this type of therapy, including respiratory distress syndrome (RDS), chronic obstructive pulmonary disease (COPD), asthma, pulmonary infections (e.g. tuberculosis, Yersinia pestis infection, fungal infections, bacterial infections, and viral infections), lung cancer, cystic fibrosis (CF), pulmonary fibrosis, and pulmonary arterial hypertension. Modification of size and surface property renders nanoparticles to be targeted to specific sites, which can serve a vital role in innovative pulmonary drug delivery. The nanocarrier type chosen depends on the intended purpose of the formulation and intended physiological target. Liquid nanocarriers and solid-state nanocarriers can carry hydrophilic and hydrophobic drugs (e.g. small molecular weight drug molecules, large molecular weight drugs, peptide drugs, and macromolecular biological drugs), while surface modification with polymer can provide cellular targeting, controlled drug release, and/or evasion of phagocytosis by immune cells, depending on the polymer type. Polymeric nanocarriers have versatile architectures, such as linear, branched, and dendritic forms. In addition to the colloidal dispersion liquid state, the various types of nanoparticles can be formulated into the solid state, offering important unique advantages in formulation versatility and enhanced stability of the final product. This chapter describes the different types of nanocarriers, types of inhalation aerosol device platforms, liquid aerosols, respirable powders, and particle engineering design technologies for inhalation aerosols.

Modification of the hydrogen compression properties of Zr–Fe–Cr–V-based alloys through Ti doping

Hydrogen refueling stations typically rely on compressors to increase the pressure of hydrogen received from long-tube trailers, enabling efficient refill of hydrogen storage tanks. However, mechanical hydrogen compressors are unable to effectively harness residual hydrogen below 6 MPa in long-tube trailers. Herein, we developed a ZrFe2-based hydrogen compression alloy to enhance the hydrogen pressure that meets the input pressure requirement of mechanical hydrogen compressors. Specifically, the co-substitution of Cr and V for Fe was conducted to reduce the plateau slope and hysteresis, and Ti was introduced to partially substitute Zr to regulate the plateau pressure. The effects of Ti on the structure and hydrogen storage properties of Zr–Fe–Cr-based alloys have been investigated by first-principles calculations, wherein Zr1-xTixFe1.7Cr0.2V0.1 (x = 0, 0.1, 0.2, 0.3, 0.4) alloys were designed and synthesized. The optimized Zr0.8Ti0.2Fe1.7Cr0.2V0.1 alloy provided a hydrogen absorption capacity of 1.22 wt% under 3.88 MPa H2 pressure at 300 K and achieved an effective hydrogen compression capacity of 1.07 wt% at 355 K at an H2 desorption pressure of 6.36 MPa. This advancement holds great promise for the efficient utilization of residual hydrogen at approximately 6 MPa in long-tube trailers, thus leading to a significant improvement in hydrogen transportation efficiency.

A comprehensive gas chromatography electron ionization high resolution mass spectrometry study of a new steroidal selective androgen receptor modulator (SARM) compound S42.

The synthetic 20-keto-steroid S42 (1) demonstrated selective androgen receptor modulator (SARM) properties in preclinical studies and, consequently, received growing attention also in the context of sports drug testing programs. Fundamental understanding of the behavior of S42 (1) and of relevant derivatives in gas chromatography-electron ionization MS experiments at high resolution (GC-EI-HRMS) is indispensable to develop a reliable qualitative and quantitative doping control method for S42 (1) and its metabolites in body fluid matrices. We present important fundamental mechanistic data on the EI fragmentation behavior of S42 (1) and of silyl ether derivatives as well as of stable isotope-labelled reference material.

Mechanical and tribological characterization of vacuum pressurized impregnation (VPI) treated bamboo fiber-reinforced polymer (FRP) composites with jute mat layer under fretting wear conditions

ABSTRACT The study explored the performance of VPI-treated bamboo fiber reinforced FRP laminated composites, focusing on fretting wear and mechanical behavior with various chemical treatments. FTIR analysis revealed that NaOH treatment effectively removed hemicelluloses and lignin, with peak shifts at 3330, 2918, and 1420 cm−1, while tannic acid induced peak shifts at 1640 and 1500 cm−1, indicating cellulose interactions. Phosphoric acid treatment reduced intensity at 3340 and 2890 cm−1, suggesting cellulose depolymerization. TGA showed varied weight loss profiles, reflecting thermal property modifications. XRD analysis indicated changes in crystalline structure, and SEM revealed structural alterations. Tensile strengths at 0.5% weight were 216 ± 3.0 MPa for alkaline-treated bamboo fiber composite (A-BFC), 256 ± 0.01 MPa for tannic acid-treated bamboo fiber composite (T-BFC), and 281 ± 3.0 MPa for phosphoric acid-treated bamboo fiber composite (P-BFC). Fretting wear analysis demonstrated that P-BFC withstood loads up to 45N, with wear resistance improving with increased fiber content. dynamic mechanical analysis (DMA) highlighted that P-BFC exhibited the highest initial storage modulus and a tan δ peak of 69°C, compared to T-BFC and A-BFC, both at 68°C. The wear rate decreased with higher bamboo fiber content and load, showcasing the potential of VPI-treated bamboo fiber composites for applications requiring enhanced strength and wear resistance.

Об идентификации характеристик неоднородных вязкоупругих тел в рамках модели дробного порядка

Nowadays, the development of models of viscoelastic materials with complex inhomogeneous structure is one of the hottest problems of continuum mechanics. Along with classical models, fractional-differential models of viscoelasticity have become increasingly popular. In this paper, we present a model for describing steady-state oscillations of inhomogeneous viscoelastic bodies in terms of fractional-order differential operators. Taking into account the fractional order of the model operators, the corresponding form of the complex module describing the material properties is constructed. The module includes four characteristics: instantaneous and long-term elastic moduli (in the case of material inhomogeneity, they are the functions of coordinates), relaxation time and fractionality parameter. The properties of the complex module are studied, and the ranges of the model parameters, at which the rheological properties are most pronounced, are identified. A general formulation of the inverse problem (IP) on the identification of function-parameters of the model based on the acoustic sounding data is proposed. In the framework of this formulation, the inverse problems for specific objects , namely, an inhomogeneous rod and a round plate, are considered. In both model problems, the influence of the fractionalization parameter on the amplitude-frequency characteristics is analyzed. It has been found that in the vicinity of viscoelastic resonances the fractionality parameter affects the parameters of the oscillatory process most significantly, which is typical for such problems. A solution to the nonlinear IPs under consideration is constructed based on the linearization method, which also serve as basis for the iterative processes supplemented with the elements of the projection approach. This allows one to determine corrections to the required functions in the specified classes of functions using regularization. For both IPs, a series of computational experiments were carried out. The analysis of the experimental results made it possible to formulate recommendations for the selection of optimal sensing modes.

Design and sensitivity study of a novel Z-shaped gate TFET sensor with SiGe source for chemical analyte detection

In this work, we have designed a chemical gas sensor using a Z-shaped gate tunnel FET with a SiGe source. Here, the gate material is a conducting organic polymer, which allows for the effective detection of a variety of chemical analytes. Over the course of the sensitivity investigation, several chemical analytes were exposed, including hexane, methanol, iso-propanol, and chloroform. Detecting chemical gases is feasible due to the work-function modification of the conducting polymer with exposure to the chemical gas vapors. This leads to modifications in the electrical properties of the suggested gas sensor, which serves as a sensing metric. The impact of surrounding temperature on various sensitivity parameters of the TFET-based gas sensor is also investigated. The proposed heterostructure Z-TFET (ZHS-TFET) offers a peak drain current sensitivity of 5.65 × 105 in the case of chloroform, which is four times higher than the sensitivity provided by the ZTFET sensor. Further, the suggested chemical sensor offers a higher subthreshold swing sensitivity (SSS) of 0.29 and a current ratio sensitivity (Sratio) of 3.18. As a result of its higher-sensitivity nature and improved electrostatic performance, the proposed sensor with conducting polymer as the gate metal may be able to meet the needs of the chemical and pharmaceutical industries, as well as environmental monitoring and biological diagnostics.

Microstructure versus topography: the impact of crystallographic substrate modification during ultrashort pulsed direct laser interference patterning on the antibacterial properties of Cu

Introduction: Topographic surface patterning in the micro- and nanometer scale has evolved into a well applied approach in surface functionalization following biomimetic blueprints from nature. Depending on the production process an additional impact of process-related substrate modification has to be considered in functional surface optimization. This is especially true in case of antimicrobial applications of Cu surfaces where a modification of the substrate properties might impact bactericidal efficiency.Methods: In this regard, the effect of ultrashort pulsed direct laser interference patterning on the microstructure of pure Cu and resulting antimicrobial properties was investigated alongside line-like patterning in the scale of single bacterial cells.Results and Discussion: The process-induced microstructure modification was shown to play an important role in corrosion processes on Cu surfaces in saline environment, whereas the superficial microstructure impacts both corrosive interaction and ion emission. Surprisingly, antimicrobial efficiency is not predominantly following deviating trends in Cu ion release rates but rather depends on surface topography and wettability, which was shown to be impacted by the substrate microstructure state, as well. This highlights the need of an in-depth understanding on how different surface properties are simultaneously modulated during laser processing and how their interaction has to be designed to acquire an effective surface optimization e.g., to agitate active antimicrobial surface functionalization.

Modification of Microstructural and Surface-Mechanical Properties of Nickel-Coated Copper by Ultrasonic Shot Peening with Emphasis on Scratch Response

Modification of Microstructural and Surface-Mechanical Properties of Nickel-Coated Copper by Ultrasonic Shot Peening with Emphasis on Scratch Response

Rationally designed Ru catalysts supported on TiN for highly efficient and stable hydrogen evolution in alkaline conditions

Electrocatalysis holds the key to enhancing the efficiency and cost-effectiveness of water splitting devices, thereby contributing to the advancement of hydrogen as a clean, sustainable energy carrier. This study focuses on the rational design of Ru nanoparticle catalysts supported on TiN (Ru NPs/TiN) for the hydrogen evolution reaction in alkaline conditions. The as designed catalysts exhibit a high mass activity of 20 A mg−1Ru at an overpotential of 63 mV and long-term stability, surpassing the present benchmarks for commercial electrolyzers. Structural analysis highlights the effective modification of the Ru nanoparticle properties by the TiN substrate, while density functional theory calculations indicate strong adhesion of Ru particles to TiN substrates and advantageous modulation of hydrogen adsorption energies via particle-support interactions. Finally, we assemble an anion exchange membrane electrolyzer using the Ru NPs/TiN as the hydrogen evolution reaction catalyst, which operates at 5 A cm−2 for more than 1000 h with negligible degradation, exceeding the performance requirements for commercial electrolyzers. Our findings contribute to the design of efficient catalysts for water splitting by exploiting particle-support interactions.

Analgesic Properties of Next-Generation Modulators of Endocannabinoid Signaling: Leveraging Modern Tools for the Development of Novel Therapeutics.

Targeting the endocannabinoid (eCB) signaling system for pain relief is an important treatment option that is only now beginning to be mechanistically explored. In this review, we focus on two recently appreciated cannabinoid-based targeting strategies, treatments with cannabidiol (CBD) and α/β-hydrolase domain containing 6 (ABHD6) inhibitors, which have the exciting potential to produce pain relief through distinct mechanisms of action and without intoxication. We review evidence on plant-derived cannabinoids for pain, with an emphasis on CBD and its multiple molecular targets expressed in pain pathways. We also discuss the function of eCB signaling in regulating pain responses and the therapeutic promises of inhibitors targeting ABHD6, a 2-arachidonoylglycerol (2-AG)-hydrolyzing enzyme. Finally, we discuss how the novel cannabinoid biosensor GRABeCB2.0 may be leveraged to enable the discovery of targets modulated by cannabinoids at a circuit-specific level. SIGNIFICANCE STATEMENT: Cannabis has been used by humans as an effective medicine for millennia, including for pain management. Recent evidence emphasizes the therapeutic potential of compounds that modulate endocannabinoid signaling. Specifically, cannabidiol and inhibitors of the enzyme ABHD6 represent promising strategies to achieve pain relief by modulating endocannabinoid signaling in pain pathways via distinct, nonintoxicating mechanisms of action.