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Dermatological diseases pose a significant burden on the quality of life of individuals and can be challenging to treat effectively. In this aspect, cannabinoids are gaining increasing importance due to their therapeutic potential in various disease entities including skin diseases. In this synthetic review, we comprehensively analyzed the existing literature in the field of potential dermatological applications of a lesser-known subgroup of cannabinoids, the so-called minor cannabinoids, such as cannabidivarin (CBDV), cannabidiforol (CBDP), cannabichromene (CBC), tetrahydrocannabivarin (THCV), cannabigerolic acid (CBGA), cannabigerol (CBG), cannabielsoin (CBE), cannabimovone (CBM) or cannabinol (CBN), while drawing attention to their unique pharmacological properties. We systematically searched the available databases for relevant studies and analyzed the data to provide an overview of current thematic knowledge. We looked through the full-text, bibliographic and factographic databases, especially Scopus, Web of Science, PubMed, Polish Scientific Journals Database, and selected the most relevant papers. Our review highlights that minor cannabinoids exhibit diverse pharmacological activities, including anti-inflammatory, analgesic, antimicrobial, and anti-itch properties. Several studies have reported their efficacy in mitigating symptoms associated with dermatological diseases such as psoriasis, eczema, acne, and pruritus. Furthermore, minor cannabinoids have shown potential in regulating sebum production, a crucial factor in acne pathogenesis. The findings of this review suggest that minor cannabinoids hold therapeutic promise in the management of dermatological diseases. Further preclinical and clinical investigations are warranted to elucidate their mechanisms of action, determine optimal dosage regimens, and assess long-term safety profiles. Incorporating minor cannabinoids into dermatological therapies could potentially offer novel treatment options of patients and improve their overall well-being.

This study aims to evaluate the usefulness and effectiveness of four machine learning (ML) models for modelling cyanobacteria blue-green algae ( CBGA ) at two rivers located in the USA. The proposed modelling framework was based on establishing a link between five water quality variables and the concentration of CBGA. For this purpose, artificial neural network (ANN), extreme learning machine (ELM), random forest regression (RFR), and random vector functional link ( RVFL ) are developed. First, the four models were developed using only water quality variables. Second, based on the results of the first, a new modelling strategy was introduced based on preprocessing signal decomposition. Hence, the empirical mode decomposition (EMD), the variational mode decomposition (VMD), and the empirical wavelet transform (EWT) were used for decomposing the water quality variables into several subcomponents, and the obtained intrinsic mode functions (IMFs) and multiresolution analysis (MRA) components were used as new input variables for the ML models. Results of the present investigation show that (i) using single models, good predictive accuracy was obtained using the RFR model exhibiting an R and NSE values of ≈0.914 and ≈0.833 for the first station, and ≈0.944 and ≈0.884 for the second station, while the others models, i.e., ANN, RVFL, and ELM, have failed to provide a good estimation of the CBGA; (ii) the decomposition methods have contributed to a significant improvement of the individual models performances; (iii) among the thee decomposition methods, the EMD was found to be superior to the VMD and EWT; and (iv) the ANN and RFR were found to be more accurate compared to the ELM and RVFL models, exhibiting high numerical performances with R and NSE values of approximately ≈0.983, ≈0.967, and ≈0.989 and ≈0.976, respectively. Graphical abstract

The study of hemp-based cannabinoids has focused primarily on cannabidiol (CBD). however, naturally synthesizes cannabidiolic acid (CBDA) as opposed to the better-known neutral derivative. The precursor to cannabidiolic CBDA is cannabigerolic acid (CBGA) and cultivar extracts that contain both acidic cannabinoids are available as animal supplements. Pharmacokinetically these acidic cannabinoids are often superior to the neutral cannabinoids. The combinations of cannabinoids may affect their bioavailability and has not been well studied. Pharmacokinetics and safety of 90 day administration of a combination of CBGA and CBDA were examined in dogs. Eight adult beagles between 10 and 11 kg were provided a whole hemp blended extract containing primarily CBDA (1 mg/kg) and CBGA (1 mg/kg). Initial single dose 24-h pharmacokinetics were performed, and from day 2-90 dogs were dosed similarly at 7 a.m. and 3 p.m. daily and serum concentrations relative to steady state were examined at days 27, 57 and 90. Complete blood counts, serum chemistry and physical examination were performed at these time points to examine physiological effects. Both CBDA and CBGA were detected in the bloodstream with AUC geometric means of 1,383 ng-h/mL and 930 ng-h/mL, respectively, on 24 h pharmacokinetics assessment. Both minor cannabinoids cannabichromenic acid (CBCA) and tetrahydrocannabinolic acid (THCA) were also observed throughout the trial, while neutral cannabinoids such as cannabidiol (CBD) could not be found. Monthly cannabinoid analysis revealed both CBDA and CBGA in the range of 10-175 ng/mL 6 h after morning dosing for all dogs. THCA and CBCA were observed in the serum of dogs at significant concentrations in the 5-75 ng/mL range. All physical exam findings and blood work were unremarkable. An equal blend of primarily CBDA and CBGA whole hemp acidic cannabinoid rich oil in soft gel appears to be well tolerated by dogs over a 90 day period with no adverse events. Pharmacokinetics are like other CBDA and CBGA studies in dogs with surprising concentrations of the other minor cannabinoids THCA and CBCA. Considering the favorable absorption/retention profile of the acidic cannabinoids, further research for therapeutic interventions for inflammatory conditions and organ dysfunction should be considered.

Cannabis sativa yields a wide range of bioactive compounds, including terpenes, flavonoids, and cannabinoids. Tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA), cannabigerolic acid (CBGA), and cannabichromenic acid (CBCA) are the acidic biosynthetic precursors of the neutral cannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), which have been the subject of much research. This review examines the biosynthesis, decarboxylation, molecular pharmacology, and therapeutic significance of acidic cannabinoids, intending to address a significant knowledge gap. Peer-reviewed literature from major scientific databases was used in a systematic narrative review with an emphasis on investigations of acidic cannabinoid chemistry, pharmacology, pharmacokinetics, and disease-specific applications. According to the reviewed data, acidic cannabinoids exhibit unique biological activities that distinguish them from their neutral counterparts. These include neuroprotective, anti-inflammatory, anticonvulsant, and anti-proliferative actions, which are mediated by molecular targets such as serotonin 5-HT1A receptors, cyclooxygenase-2 (COX-2), transient receptor potential (TRP) channels, and peroxisome proliferator-activated receptor-γ (PPARγ). Acidic cannabinoids are more appealing for therapeutic usage in children and the elderly, considering that they are not intoxicating like THC; however, this distinction applies primarily to non‑heated consumption. Chemical instability, low bioavailability, and a dearth of controlled human trials impede clinical translation despite their potential. According to the findings, acidic cannabinoids are an underutilized yet potentially valuable class of precision medicines. In this study, we outline existing understanding on acidic cannabinoids, discuss their production and transformation, and identify research needs that could influence cannabis science research.

Objective Cannabigerolic acid (CBGA), a precursor cannabinoid in Cannabis sativa , has recently been found to have anticonvulsant properties in the Scn1a +/- mouse model of Dravet syndrome. Poor brain penetration and chemical instability of CBGA limits its potential as an anticonvulsant therapy. Here, we examined whether CBGA methyl ester, a more stable analogue of CBGA, might have superior pharmacokinetic and anticonvulsant properties. In addition, we examined whether olivetolic acid, the biosynthetic precursor to CBGA with a truncated (des-geranyl) form, might possess minimum structural requirements for anticonvulsant activity. We also examined whether olivetolic acid and CBGA methyl ester retain activity at the epilepsy-relevant drug targets of CBGA: G-protein-coupled receptor 55 (GPR55) and T-type calcium channels. Methods The brain and plasma pharmacokinetic profiles of CBGA methyl ester and olivetolic acid were examined following 10 mg/kg intraperitoneal (i.p.) administration in mice ( n = 4). The anticonvulsant potential of each was examined in male and female Scn1a +/- mice ( n = 17–19) against hyperthermia-induced seizures (10–100 mg/kg, i.p.). CBGA methyl ester and olivetolic acid were also screened in vitro against T-type calcium channels and GPR55 using intracellular calcium and ERK phosphorylation assays, respectively. Results CBGA methyl ester exhibited relatively limited brain penetration (13%), although somewhat superior to that of 2% for CBGA. No anticonvulsant effects were observed against thermally induced seizures in Scn1a +/- mice. Olivetolic acid also showed poor brain penetration (1%) but had a modest anticonvulsant effect in Scn1a +/- mice increasing the thermally induced seizure temperature threshold by approximately 0.4°C at a dose of 100 mg/kg. Neither CBGA methyl ester nor olivetolic acid displayed pharmacological activity at GPR55 or T-type calcium channels. Conclusions Olivetolic acid displayed modest anticonvulsant activity against hyperthermia-induced seizures in the Scn1a +/- mouse model of Dravet syndrome despite poor brain penetration. The effect was, however, comparable to the known anticonvulsant cannabinoid cannabidiol in this model. Future studies could explore the anticonvulsant mechanism(s) of action of olivetolic acid and examine whether its anticonvulsant effect extends to other seizure types.

Cannabinoids are a major class of compounds produced by the plant Cannabis sativa. Previous work has demonstrated that the main cannabinoids cannabidiol (CBD) and tetrahydrocannabinol (THC) can have some beneficial effects on pain, inflammation, epilepsy, and chemotherapy-induced nausea and vomiting. While CBD and THC represent the two major plant cannabinoids, some hemp varieties with enzymatic deficiencies produce mainly cannabigerolic acid (CBGA). We recently reported that CBGA has a potent inhibitory effect on both Store-Operated Calcium Entry (SOCE) via inhibition of Calcium Release-Activated Calcium (CRAC) channels as well as currents carried by the channel-kinase TRPM7. Importantly, CBGA prevented kidney damage and suppressed mRNA expression of inflammatory cytokines through inhibition of these mechanisms in an acute nephropathic mouse model. In the present study, we investigate the most common major and minor cannabinoids to determine their potential efficacy on TRPM7 channel function. We find that approximately half of the tested cannabinoids suppress TRPM7 currents to some degree, with CBGA having the strongest inhibitory effect on TRPM7. We determined that the CBGA-mediated inhibition of TRPM7 requires a functional kinase domain, is sensitized by both intracellular Mg⋅ATP and free Mg2+ and reduced by increases in intracellular Ca2+. Finally, we demonstrate that CBGA inhibits native TRPM7 channels in a B lymphocyte cell line. In conclusion, we demonstrate that CBGA is the most potent cannabinoid in suppressing TRPM7 activity and possesses therapeutic potential for diseases in which TRPM7 is known to play an important role such as cancer, stroke, and kidney disease. Graphical Abstract Graphical Abstract

This paper proposes a new hybrid master–slave optimization approach to address the problem of the optimal placement and sizing of distribution static compensators (D-STATCOMs) in electrical distribution grids. The optimal location of the D-STATCOMs is identified by implementing the classical and well-known Chu and Beasley genetic algorithm, which employs an integer codification to select the nodes where these will be installed. To determine the optimal sizes of the D-STATCOMs, a second-order cone programming reformulation of the optimal power flow problem is employed with the aim of minimizing the total costs of the daily energy losses. The objective function considered in this study is the minimization of the annual operative costs associated with energy losses and installation investments in D-STATCOMs. This objective function is subject to classical power balance constraints and device capabilities, which generates a mixed-integer nonlinear programming model that is solved with the proposed genetic-convex strategy. Numerical validations in the 33-node test feeder with radial configuration show the proposed genetic-convex model’s effectiveness to minimize the annual operative costs of the grid when compared with the optimization solvers available in GAMS software.

In this paper, we analyze the residual stress of different components of the crystal structures of electronic device materials following exposure to elevated temperatures using a combination of experimental tests and finite element simulations. X-ray diffraction (XRD) and LXRD micro-area residual stress analyzer were employed to determine the residual strain and stress of the CBGA sample encapsulation cover and solder joints. Subsequently, the experimental data were utilized to verify the accuracy of the simulation. The discrepancy between experimental measurements and simulation outcomes of the residual stress following reflow soldering of CBGA-assembled micro-solder joints is below 14%. The analysis also included thermal warping deformation of the CBGA encapsulation cover and how the residual stress was influenced by the diameter, spacing, and height of the solder joints. The study reveals that the residual stress following reflow soldering of BGA solder joints is non-uniformly distributed within the array. Within a single solder joint, residual stress gradually increases in distribution from its middle to the point where it make contact with the PCB and chip, with the highest level of residual stress observed where the solder joint contacts the chip. The variation in material parameters, such as the coefficient of thermal expansion, is the primary cause of thermal warping deformation on the surface of CBGA encapsulation covers. Three primary factors significantly impact the residual stress on BGA solder joints: solder joint diameter, spacing, and height. The maximum value is inversely proportional to the height of the solder joints and the residual stress. Conversely, the diameter and spacing of the joints are positively proportional to the highest value. When the diameter of the solder joint is increased from 0.55 mm to 0.75 mm, the maximum residual stress in the BGA solder joint increases from 37.243 MPa to 36.835 MPa. Conversely, increasing the height of the solder joint from 0.36 mm to 0.44 mm reduces the stress from 39.776 MPa to 36.835 MPa.

Y2O3 addition has a significant influence on the crystallization, thermal, mechanical, and electrical properties of BaO-Al2O3-B2O3-SiO2 (BABS) glass–ceramics. Semi-quantitative calculation based on x-ray diffraction demonstrated that with increasing Y2O3 content, both the crystallinity and the phase content of cristobalite gradually decreased. It is effective for the additive Y2O3 to inhibit the formation of cristobalite phase with a large coefficient of thermal expansion value. The flexural strength and the Young’s modulus, thus, are remarkably increased from 140 MPa to 200 MPa and 56.5 GPa to 63.7 GPa, respectively. Also, the sintering kinetics of BABS glass–ceramics with various Y2O3 were investigated using the isothermal sintering shrinkage curve at different sintering temperatures. The sintering activation energy Q sharply decreased from 99.8 kJ/mol to 81.5 kJ/mol when 0.2% Y2O3 was added, which indicated that a small amount of Y2O3 could effectively promote the sintering procedure of BABS glass–ceramics.