A copula-based method of risk prediction for autonomous underwater gliders in dynamic environments.

Autonomous underwater gliders (AUGs) are effective platforms for oceanic research and environmental monitoring. However, complex underwater environments with uncertainties could pose the risk of vehicle loss during their missions. It is therefore essential to conduct risk prediction to assist decision making for safer operations. The main limitation of current studies for AUGs is the lack of a tailored method for risk analysis considering both dynamic environments and potential functional failures of the vehicle. Hence, this study proposed a copula-based approach for evaluating the risk of AUG loss in dynamic underwater environments. The developed copula Bayesian network (CBN) integrated copula functions into a traditional Bayesian belief network (BBN), aiming to handle nonlinear dependencies among environmental variables and inherent technical failures. Specifically, potential risk factors with causal effects were captured using the BBN. A Gaussian copula was then employed to measure correlated dependencies among identified risk factors. Furthermore, the dependence analysis and CBN inference were performed to assess the risk level of vehicle loss given various environmental observations. The effectiveness of the proposed method was demonstrated in a case study, which considered deploying a Slocum G1 Glider in a real water region. Risk mitigation measures were provided based on key findings. This study potentially contributes a tailored tool of risk prediction for AUGs in dynamic environments, which can enhance the safety performance of AUGs and assist in risk mitigation for decision makers.

Heterogeneous Diamond-cBN Composites with Superb Toughness and Hardness.

The traditional hardness-toughness tradeoff poses a substantial challenge for the development of superhard materials. Due to strong covalent bonds and intrinsic brittleness, the full advantage of microstructure engineering for enhanced mechanical properties requires further exploration in superhard materials. Here heterogeneous diamond-cBN composites were synthesized from a carefully prepared precursor (hBN microflakes uniformly wrapped by onion carbon nanoparticles) through phase transitions under high pressure and high temperature. The synthesized composites inherit the architecture of the precursors: cBN regions with an anisotropic profile that spans several micrometers laterally and several hundred nanometers in thickness are embedded in a nanograined diamond matrix with high-density nanotwins. A significantly high fracture toughness of 16.9 ± 0.8 MPa m1/2 is achieved, far beyond those of single-crystal diamond and cBN, without sacrificing hardness. A detailed TEM analysis revealed multiple toughening mechanisms closely related to the microstructure. This work sheds light on microstructure engineering in superhard materials for excellent mechanical properties.

Anti-Inflammatory Effects of Minor Cannabinoids CBC, THCV, and CBN in Human Macrophages.

Inflammation is a natural response of the body to signals of tissue damage or infection caused by pathogens. However, when it becomes imbalanced, it can lead to various disorders such as cancer, obesity, cardiovascular problems, neurological conditions, and diabetes. The endocannabinoid system, which is present throughout the body, plays a regulatory role in different organs and influences functions such as food intake, pain perception, stress response, glucose tolerance, inflammation, cell growth and specialization, and metabolism. Phytocannabinoids derived from Cannabis sativa can interact with this system and affect its functioning. In this study, we investigate the mechanisms underlying the anti-inflammatory effects of three minor phytocannabinoids including tetrahydrocannabivarin (THCV), cannabichromene (CBC), and cannabinol (CBN) using an in vitro system. We pre-treated THP-1 macrophages with different doses of phytocannabinoids or vehicle for one hour, followed by treating the cells with 500 ng/mL of LPS or leaving them untreated for three hours. To induce the second phase of NLRP3 inflammasome activation, LPS-treated cells were further treated with 5 mM ATP for 30 min. Our findings suggest that the mitigation of the PANX1/P2X7 axis plays a significant role in the anti-inflammatory effects of THCV and CBC on NLRP3 inflammasome activation. Additionally, we observed that CBC and THCV could also downregulate the IL-6/TYK-2/STAT-3 pathway. Furthermore, we discovered that CBN may exert its inhibitory impact on the assembly of the NLRP3 inflammasome by reducing PANX1 cleavage. Interestingly, we also found that the elevated ADAR1 transcript responded negatively to THCV and CBC in LPS-macrophages, indicating a potential involvement of ADAR1 in the anti-inflammatory effects of these two phytocannabinoids. THCV and CBN inhibit P-NF-κB, downregulating proinflammatory gene transcription. In summary, THCV, CBC, and CBN exert anti-inflammatory effects by influencing different stages of gene expression: transcription, post-transcriptional regulation, translation, and post-translational regulation.

Direct Quantitation of Phytocannabinoids by One-Dimensional 1H qNMR and Two-Dimensional 1H-1H COSY qNMR in Complex Natural Mixtures.

The widespread use of phytocannabinoids or cannabis extracts as ingredients in numerous types of products, in combination with the legal restrictions on THC content, has created a need for the development of new, rapid, and universal analytical methods for their quantitation that ideally could be applied without separation and standards. Based on previously described qNMR studies, we developed an expanded 1H qNMR method and a novel 2D-COSY qNMR method for the rapid quantitation of ten major phytocannabinoids in cannabis plant extracts and cannabis-based products. The 1H qNMR method was successfully developed for the quantitation of cannabidiol (CBD), cannabidiolic acid (CBDA), cannabinol (CBN), cannabichromene (CBC), cannabichromenic acid (CBCA), cannabigerol (CBG), cannabigerolic acid (CBGA), Δ9-tetrahydrocannabinol (Δ9-THC), Δ9-tetrahydrocannabinolic acid (Δ9-THCA), Δ8-tetrahydrocannabinol (Δ8-THC), cannabielsoin (CBE), and cannabidivarin (CBDV). Moreover, cannabidivarinic acid (CBDVA) and Δ9-tetrahydrocannabivarinic acid (Δ9-THCVA) can be distinguished from CBDA and Δ9-THCA respectively, while cannabigerovarin (CBGV) and Δ8-tetrahydrocannabivarin (Δ8-THCV) present the same 1H-spectra as CBG and Δ8-THC, respectively. The COSY qNMR method was applied for the quantitation of CBD, CBDA, CBN, CBG/CBGA, and THC/THCA. The two methods were applied for the analysis of hemp plants; cannabis extracts; edible cannabis medium-chain triglycerides (MCT); and hemp seed oils and cosmetic products with cannabinoids. The 1H-NMR method does not require the use of reference compounds, and it requires only a short time for analysis. However, complex extracts in 1H-NMR may have a lot of signals, and quantitation with this method is often hampered by peak overlap, with 2D NMR providing a solution to this obstacle. The most important advantage of the COSY NMR quantitation method was the determination of the legality of cannabis plants, extracts, and edible oils based on their THC/THCA content, particularly in the cases of some samples for which the determination of THC/THCA content by 1H qNMR was not feasible.

Cellular blue nevus tumor presenting as a submandibular lymph node in a 16-year-old.

The cellular blue nevus tumor is a type of dendritic melanocytic nevus that is typically benign and exceedingly rare. The incidence of all blue nevi is about 1%, usually affecting the adult population and appearing on the extremities, sacrococcygeal or gluteal regions. There have only been a handful of case reports cited in the literature where cellular blue nevi present in the head and neck region, usually affecting the scalp and young adult population (7, 8). As such, it is exceedingly rare to encounter a cellular blue nevus tumor in the neck or infiltrating into neck lymph nodes. Here we report a rare case of a cellular blue nevus tumor presenting as a right neck mass in a pediatric 16-year-old patient, shown to invade into the submandibular lymph node and surrounding soft tissue. It is important to be aware of the cellular blue nevus tumor as a differential diagnosis in pediatric neck masses. Histological evaluation is necessary to determine tumor aggression and malignant potential which can guide further treatment in pediatric patients.

Recovery preparedness of global air transport influenced by COVID-19 pandemic: Policy intervention analysis.

The outbreak of COVID-19 constitutes an unprecedented disruption globally, in which risk management framework is on top priority in many countries. Travel restriction and home/office quarantine are some frequently utilized non-pharmaceutical interventions, which bring the worst crisis of airline industry compared with other transport modes. Therefore, the post-recovery of global air transport is extremely important, which is full of uncertainty but rare to be studied. The explicit/implicit interacted factors generate difficulties in drawing insights into the complicated relationship and policy intervention assessment. In this paper, a Causal Bayesian Network (CBN) is utilized for the modelling of the post-recovery behaviour, in which parameters are synthesized from expert knowledge, open-source information and interviews from travellers. The tendency of public policy in reaction to COVID-19 is analyzed, whilst sensitivity analysis and forward/backward belief propagation analysis are conducted. Results show the feasibility and scalability of this model. On condition that no effective health intervention method (vaccine, medicine) will be available soon, it is predicted that nearly 120 days from May 22, 2020, would be spent for the number of commercial flights to recover back to 58.52%-60.39% on different interventions. This intervention analysis framework is of high potential in the decision making of recovery preparedness and risk management for building the new normal of global air transport.

Modulation of human platelet activation and in vivo vascular thrombosis by columbianadin: regulation by integrin αIIbß3 inside-out but not outside-in signals.

BACKGROUND: Columbianadin (CBN) is one of the main coumarin constituents isolated from Angelica pubescens. The pharmacological value of CBN is well demonstrated, especially in the prevention of several cancers and analgesic activity. A striking therapeutic target for arterial thrombosis is inhibition of platelet activation because platelet activation significantly contributes to these diseases. The current study examined the influence of CBN on human platelet activation in vitro and vascular thrombotic formation in vivo. METHODS: Aggregometry, immunoblotting, immunoprecipitation, confocal microscopic analysis, fibrin clot retraction, and thrombogenic animals were used in this study. RESULTS: CBN markedly inhibited platelet aggregation in washed human platelets stimulated only by collagen, but was not effective in platelets stimulated by other agonists such as thrombin, arachidonic acid, and U46619. CBN evidently inhibited ATP release, intracellular ([Ca2+]i) mobilization, and P-selectin expression. It also inhibited the phosphorylation of phospholipase C (PLC)γ2, protein kinase C (PKC), Akt (protein kinase B), and mitogen-activated protein kinases (MAPKs; extracellular signal-regulated kinase [ERK] 1/2 and c-Jun N-terminal kinase [JNK] 1/2, but not p38 MAPK) in collagen-activated platelets. Neither SQ22536, an adenylate cyclase inhibitor, nor ODQ, a guanylate cyclase inhibitor, reversed the CBN-mediated inhibition of platelet aggregation. CBN had no significant effect in triggering vasodilator-stimulated phosphoprotein phosphorylation. Moreover, it markedly hindered integrin αIIbß3 activation by interfering with the binding of PAC-1; nevertheless, it had no influences on integrin αIIbß3-mediated outside-in signaling such as adhesion number and spreading area of platelets on immobilized fibrinogen as well as thrombin-stimulated fibrin clot retraction. Additionally, CBN did not attenuate FITC-triflavin binding or phosphorylation of proteins, such as integrin ß3, Src, and focal adhesion kinase, in platelets spreading on immobilized fibrinogen. In experimental mice, CBN increased the occlusion time of thrombotic platelet plug formation. CONCLUSION: This study demonstrated that CBN exhibits an exceptional activity against platelet activation through inhibition of the PLCγ2-PKC cascade, subsequently suppressing the activation of Akt and ERKs/JNKs and influencing platelet aggregation. Consequently, this work provides solid evidence and considers that CBN has the potential to serve as a therapeutic agent for the treatment of thromboembolic disorders.

New trends in cannabis potency in USA and Europe during the last decade (2008-2017).

Through the potency monitoring program at the University of Mississippi supported by National Institute on Drug Abuse (NIDA), a total of 18108 samples of cannabis preparations have been analyzed over the last decade, using a validated GC/FID method. The samples are classified as sinsemilla, marijuana, ditchweed, hashish, and hash oil (now referred to as cannabis concentrate). The number of samples received over the last 5 years has decreased dramatically due to the legalization of marijuana either for medical or for recreational purposes in many US states. The results showed that the mean Δ9-THC concentration has increased dramatically over the last 10 years, from 8.9% in 2008 to 17.1% in 2017. The mean Δ9-THC:CBD ratio also rose substantially from 23 in 2008 to 104 in 2017. There was also marked increase in the proportion of hash oil samples (concentrates) seized (0.5-4.7%) and their mean Δ9-THC concentration (6.7-55.7%) from 2008 to 2017. Other potency monitoring programs are also present in several European countries such as The Netherlands, United Kingdom, France, and Italy. These programs have also documented increases in Δ9-THC concentrations and Δ9-THC:CBD ratios in cannabis. These trends in the last decade suggest that cannabis is becoming an increasingly harmful product in the USA and Europe.

A Randomized, Double-Blind, Placebo-Controlled Trial to Assess the Effectiveness and Safety of Melatonin and Three Formulations of Floraworks Proprietary TruCBN™ for Improving Sleep.

The phytocannabinoid cannabinol (CBN) has a potential mechanism of action as an alternative sleep aid but there is minimal evidence to support its effectiveness. The aim of this randomized, double-blind, placebo-controlled study was to assess the safety and effects of three formulations of a hemp-derived CBN sleep aid, TruCBN™ [25 mg (n = 206), 50 mg (n = 205), 100 mg (n = 203)], on sleep quality (PROMIS Sleep Disturbance 8A), relative to placebo (n = 204). The effectiveness and safety of these formulations relative to 4 mg of melatonin (n = 202) was assessed. Exploratory measures were stress (PROMIS Stress 4A), anxiety (Anxiety 4A), pain (PROMIS™ PEG), and well-being (WHO 5). All groups and the 4 mg melatonin group experienced significant improvement in sleep quality relative to the placebo group with no significant differences between any group and the melatonin group. Participants taking 100 mg showed a larger decrease in stress compared to the placebo group. There were no significant differences in anxiety, pain, well-being, or the frequency of side effects between any group and the placebo group. There was no significant difference in improvements in sleep quality between any of the treatment groups and the 4 mg melatonin group. Orally ingested CBN, at 25 mg, 50 mg, and 100 mg, is a safe and effective alternative for the improvement of sleep.

The Safety and Comparative Effectiveness of Non-Psychoactive Cannabinoid Formulations for the Improvement of Sleep: A Double-Blinded, Randomized Controlled Trial.

BACKGROUND: Clinical evidence on the use of cannabidiol (CBD) for sleep remains limited. Even fewer studies have tested the comparative effectiveness of cannabinoid formulations found within CBD products used for sleep or how they compare to other complementary therapies such as melatonin. METHODS: Participants (N = 1,793 adults experiencing symptoms of sleep disturbance) were randomly assigned to receive a 4-week supply of 1 of 6 products (all capsules) containing either 15 mg CBD or 5 mg melatonin, alone or in combination with minor cannabinoids. Sleep disturbance was assessed over a period of 5 weeks (baseline week and 4 weeks of product use) using Patient-Reported Outcomes Measurement Information System (PROMIS™) Sleep Disturbance SF 8A, administered via weekly online surveys. A linear mixed-effects regression model was used to assess the differences in the change in sleep disturbance through time between each active product arm and CBD isolate. RESULTS: All formulations exhibited a favorable safety profile (12% of participants reported a side effect and none were severe) and led to significant improvements in sleep disturbance (p < 0.001 in within-group comparisons). Most participants (56% to 75%) across all formulations experienced a clinically important improvement in their sleep quality. There were no significant differences in effect, however, between 15 mg CBD isolate and formulations containing 15 mg CBD and 15 mg cannabinol (CBN), alone or in combination with 5 mg cannabichromene (CBC). There were also no significant differences in effect between 15 mg CBD isolate and formulations containing 5 mg melatonin, alone or in combination with 15 mg CBD and 15 mg CBN. CONCLUSIONS: Our findings suggest that chronic use of a low dose of CBD is safe and could improve sleep quality, though these effects do not exceed that of 5 mg melatonin. Moreover, the addition of low doses of CBN and CBC may not improve the effect of formulations containing CBD or melatonin isolate.

Bi-layer cBN-based composites reinforced with oxide and non-oxide microfibers of refractory compounds.

Research into new composites utilizing cubic boron nitride (PcBN) shows promise for enhancing cutting tool performance. The unique properties of these materials stem from the addition of microfibers made of refractory compounds to their structure. This study looks at developing two-layer composites based on cBN group BL, reinforced with SiCw and Al2O3w microfibers. The goal is to improve tool stability when cutting hardened steels with impact loads. PcBN composite samples were made by sintering a mixture of cBN powder with bundles and microfibers under 7.7 GPa pressure. Bond material selection was based on analyzing the relationship between Poisson's ratio (η) and plasticity parameter (G/B). The density, Young's modulus, Poisson's ratio, and hardness of the composites were determined, and the microstructure of samples with TiCN bond was studied. Tool-life tests were conducted on two-layer cutting inserts made of PcBN reinforced with SiCw and Al2O3w microfibers during the machining of hardened KhVG steel (HRC 55) under impact loads at cutting speeds of 100 and 200 m/min.

Investigation of MAF for Finishing the Inner Wall of Super-Slim Cardiovascular Stents Tube.

The internal wall of cardiovascular stent tubing produced by a drawing process has defects such as pits and bumps, making the surface rough and unusable. In this research, the challenge of finishing the inner wall of a super-slim cardiovascular stent tube was solved by magnetic abrasive finishing. Firstly, a spherical CBN magnetic abrasive was prepared by a new method, plasma molten metal powders bonding with hard abrasives; then, a magnetic abrasive finishing device was developed to remove the defect layer from the inner wall of ultrafine long cardiovascular stent tubing; finally, response surface tests were performed and parameters were optimized. The results show that the prepared spherical CBN magnetic abrasive has a perfect spherical appearance; the sharp cutting edges cover the surface layer of the iron matrix; the developed magnetic abrasive finishing device for a ultrafine long cardiovascular stent tube meets the processing requirements; the process parameters are optimized by the established regression model; and the inner wall roughness (Ra) of the nickel-titanium alloy cardiovascular stents tube is reduced from 0.356 µm to 0.083 µm, with an error of 4.3% from the predicted value. Magnetic abrasive finishing effectively removed the inner wall defect layer and reduced the roughness, and this solution provides a reference for polishing the inner wall of ultrafine long tubes.

Synthesis of cBN-hBN-SiCw Nanocomposite with Superior Hardness, Strength, and Toughness.

Nanocomposites with one-dimensional (1D) and two-dimensional (2D) phases can demonstrate superior hardness, fracture toughness, and flexural strength. Cubic boron nitride-hexagonal boron nitride-silicon carbide whiskers (cBN-hBN-SiCw) nanocomposites with the simultaneous containing 1D SiCw and 2D hBN phases were successfully fabricated via the high-pressure sintering of a mixture of SiCw and cBN nanopowders. The hBN was generated in situ via the limited phase transition from cBN to hBN. Nanocomposites with 25 wt.% SiCw exhibited optimal comprehensive mechanical properties with Vickers hardness of 36.5 GPa, fracture toughness of 6.2 MPa·m1/2, and flexural strength of 687.4 MPa. Higher SiCw contents did not significantly affect the flexural strength but clearly decreased the hardness and toughness. The main toughening mechanism is believed to be a combination of hBN inter-layer sliding, SiCw pull-out, crack deflection, and crack bridging.

An efficient and simple SERS approach for trace analysis of tetrahydrocannabinol and cannabinol and multi-cannabinoid detection.

Many countries have legalized cannabis and its derived products for multiple purposes. Consequently, it has become necessary to develop a rapid, effective, and reliable tool for detecting delta-9-tetrahydrocannabinol (THC) and cannabinol (CBN), which are important biologically active compounds in cannabis. Herein, we have fabricated SERS chips by using glancing angle deposition and tuned dimensions of silver nanorods (AgNRs) for detecting THC and CBN at low concentrations. Experimental and computational results showed that the AgNR substrate with film thickness (or nanorod length) of 150 nm, corresponding to nanorod diameter of 79 nm and gap between nanorods of 23 nm, can effectively sense trace THC and CBN with good reproducibility and sensitivity. Due to limited spectral studies of the cannabinoids in previous reports, this work also explored towards identifying characteristic Raman lines of THC and CBN. This information is critical to further reliable data analysis and interpretation. Moreover, multianalyte detection of THC and CBN in a mixture was successfully demonstrated by applying an open-source independent component analysis (ICA) model. The overall method is fast, sensitive, and reliable for sensing trace THC and CBN. The SERS chip-based method and spectral results here are useful for a variety of cannabis testing applications, such as product screening and forensic investigation.

Effect of the Granularity of Cubic Boron Nitride Vitrified Grinding Wheels on the Planar Technical Blades Sharpening Process.

The most widely used method for shaping technical blades is grinding with abrasive tools made of cubic boron nitride (cBN) grains and vitrified bond. The goal of this work was to determine the effect of grinding wheel grain size (cBN grain number according to FEPA standards: B126, B181 and B251), kinematics (grinding with the circumference, face and conical surface of the wheel) and feed rate (vf = 100; 150; 200 mm/min) on the effects of the grinding process evaluated by the cutting force of the blade after machining F, blade surface texture parameters (Sa, St, Smvr, Str, Sdq, Sdr and Sbi) as well as blade surface morphology. An analysis of output quantities showed that grinding wheels made of B181 cBN grains are most favorable for shaping planar technical blades of X39Cr13 steel in the grinding process.

Study on Preparation and Grinding Performance of Vitrified Bond CBN Grinding Wheel with Controllable Porosity.

Vitrified bond cubic boron nitride (CBN) grinding wheel specimens with controllable porosity were prepared by regulating the pore former dextrin content and varying the forming pressure, and the performance of the grinding camshaft was studied. The porosity of the specimens increases with the increase in dextrin content, and decreases first and then increases with the increase in the forming pressure. The grinding experiments show that the dextrin content is negatively correlated with the grinding force and grinding temperature, while the grinding force and grinding temperature of the specimens increase and then decrease with the increase in the forming pressure. When we observe and measure the grinding surface of the specimen and workpiece, we see that the surface roughness of the specimen after grinding is smaller than that before grinding. In addition, the greater the porosity of the specimen, the rougher the surface of the workpiece after grinding.

Monitoring Cannabinoids and the Safety of the Trace Element Profile of Light Cannabis sativa L. from Different Varieties and Geographical Origin.

Non-intoxicating Cannabis sativa L. (i.e., hemp) is increasingly used for industrial, cosmetic and food applications. Despite the fact that the EU has not yet established a regulatory framework on hazardous compounds (i.e., toxic inorganic elements), the monitoring of cannabis products is of paramount importance to safeguard consumers, also in view of the species propensity to accumulate toxic metals from the environment. The aim of this work was to assess the compliance with Law n. 242/2016 and the safety of hemp inflorescences from different varieties and Italian regions by monitoring the main cannabinoids and trace elements. All samples complied with the Italian law due to a THC content <0.6% counterbalanced by high CBD levels. However, inflorescences grown in Apulia and Lombardy, and from Finola and Tiborzallasi varieties accumulated higher Cu, Co, Cr, Ni and Pb contents than products from other producing areas (i.e., Sicily and Latium) and varieties (i.e., Antal, Futura75, Kompolti and Carmagnola), being moreover above the limits set by the US Pharmacopeia. A principal component analysis confirmed that trace elements, including toxic metals, were mainly affected by the geographical origin more than the botanical variety. Overall, this study highlights the need to continuously monitor hemp products and establish the earliest related regulatory frameworks.

Structural analysis of cannabinoids against EGFR-TK leads a novel target against EGFR-driven cell lines.

Epidermal growth factor receptor (EGFR) is a member of the ErbB family of proteins and are involved in downstream signal transduction, plays prominent roles in cell growth regulation, proliferation, and the differentiation of many cell types. They are correlated with the stage and severity of cancer. Therefore, EGFRs are targeted proteins for the design of new drugs to treat cancers that overexpress these proteins. Currently, several bioactive natural extracts are being studied for therapeutic purposes. Cannabis has been reported in many studies to have beneficial medicinal effects, such as anti-inflammatory, analgesic, antibacterial, and anti-inflammatory effects, and antitumor activity. However, it is unclear whether cannabinoids reduce intracellular signaling by inhibiting tyrosine kinase phosphorylation. In this study, cannabinoids (CBD, CBG, and CBN) were simulated for binding to the EGFR-intracellular domain to evaluate the binding energy and binding mode based on molecular docking simulation. The results showed that the binding site was almost always located at the kinase active site. In addition, the compounds were tested for binding affinity and demonstrated their ability to inhibit kinase enzymes. Furthermore, the compounds potently inhibited cellular survival and apoptosis induction in either of the EGFR-overexpressing cell lines.

Cannabinol and Sleep: Separating Fact from Fiction.

In recent years, marketers of cannabis (i.e., marijuana) products have claimed that cannabinol (CBN) has unique sleep-promoting effects. Despite a plausible mechanism, it is possible that such claims are merely rooted in cannabis lore. The aim of this narrative review was to answer the question: "Is there sufficient clinical evidence to support claims that CBN has sleep-promoting effects?" A systematic search of PubMed/MEDLINE was performed to evaluate the published evidence. The abstracts of 99 human studies were screened for relevance by the author and reviewed for compliance with the inclusion criteria. The characteristics and principal findings were extracted from eight full-text articles that met inclusion criteria for detailed review. Pre-clinical and clinical research investigating the effects of CBN is dated and limited, with the preponderance of human studies occurring in the 1970-1980s with small sample sizes lacking diversity in sociodemographic characteristics. Studies specifically assessing subjective effects associated with sleep, such as sedation or fatigue, are rare. Most importantly, published clinical trials investigating associations between CBN and validated sleep questionnaires and/or formal polysomnography were not identified in this review. In addition, evidence demonstrating that CBN itself elicits cannabis-like effects in humans is mixed, with the majority of available evidence demonstrating a lack of such an effect. Consequently, there is insufficient published evidence to support sleep-related claims. Randomized controlled trials are needed to substantiate claims made by manufacturers of cannabis products containing CBN. These studies should specifically evaluate its effects on sleep through polysomnography, or at minimum, through validated sleep questionnaires, and use dosages significantly higher than those found in currently available cannabis products marketed for sleep (typically ≤5 mg). Individuals seeking cannabis-derived sleep aids should be skeptical of manufacturers' claims of sleep-promoting effects.

Peridynamic Simulation to Fracture Mechanism of CBN Grain in the Honing Wheel Dressing Process.

Regularly dressing of CBN honing wheel is an effective way to keep its sharpness and correct geometry during honing process. This study aims to understand the fracture mechanism of single CBN grain in the dressing process of honing wheel. The honing wheel dressing process was simplified into the dressing process of grinding wheel, and the bond-based Peridynamic method considering bond rotation effect was developed to investigate the progressive fracture evolution, stress characteristics, and fracture modes of CBN grains in this process. It was found that fracture evolution of CBN grains mainly underwent four stages: elastic deformation, damage initiation, crack formation, and macro fracture. In addition, the fracture initiation and propagation were mainly determined by the tensile and shear stress, where the former led to mode I fractures and the latter led to mode II fractures. The propagation of mode I fractures was stable while the propagation of mode II fracture was unstable. The results show that the Peridynamic approach has great potential to predict the fracture mechanism of CBN grain in the dressing process of honing and grinding wheels.