Domain-Selective Enzymatic Cross-linking and Etching for Shape-Morphing DNA-Linked Nanoparticle Films.

The highly programmable and responsive molecular recognition properties of DNA provide unparalleled opportunities for fabricating dynamic nanostructures capable of structural transformation in response to various external stimuli. However, they typically operate in tightly controlled environments because certain conditions (ionic strength, pH, temperature, etc.) must be met for DNA duplex formation. In this study, we adopted site-specific enzymatic ligation and DNA-based layer-by-layer thin film fabrication to build shape-morphing DNA-linked nanoparticle films operational in a broad range of environments. The ligated films remained intact in unusual conditions such as pure water and high temperature causing dissociation of DNA duplexes and showed predictable and reversible shape morphing in response to various environmental changes and DNA exchange reactions. Furthermore, domain-selective ligation combined with photoinduced interlayer mixing allowed for the fabrication of unusual edge-sealed double-layered films through midlayer etching, which is difficult to realize by other methods.

The complexity of biological control systems: An autophagy case study.

Autophagy and YAP1-WWTR1/TAZ signalling are tightly linked in a complex control system of forward and feedback pathways which determine different cellular outcomes in differing cell types at different time-points after perturbations. Here we extend our previous experimental and modelling approaches to consider two possibilities. First, we have performed additional mathematical modelling to explore how the autophagy-YAP1 crosstalk may be controlled by posttranslational modifications of components of the pathways. Second, since analogous contrasting results have also been reported for autophagy as a regulator of other transduction pathways engaged in tumorigenesis (Wnt/ß-catenin, TGF-ß/Smads, NF-kB or XIAP/cIAPs), we have considered if such discrepancies may be explicable through situations involving competing pathways and feedback loops in different cell types, analogous to the autophagy-YAP/TAZ situation. Since distinct posttranslational modifications dominate those pathways in distinct cells, these need to be understood to enable appropriate cell type-specific therapeutic strategies for cancers and other diseases.

Decreased aggressive care at the end of life among advanced cancer patients in the Republic of Korea: a nationwide study from 2012 to 2018.

BACKGROUND: This study aimed to investigate the trends of aggressive care at the end-of-life (EoL) for patients with advanced cancer in Korea and to identify factors affecting such care analyzing nationwide data between 2012 to 2018. METHODS: This was a population-based, retrospective nationwide study. We used administrative data from the National Health Insurance Service and the Korea Central Cancer Registry to analyze 125,350 patients aged 20 years and above who died within one year of a stage IV cancer diagnosis between 2012 and 2018. RESULTS: The overall aggressiveness of EoL care decreased between 2012 and 2018. In patients' last month of life, chemotherapy use (37.1% to 32.3%; p < 0.05), cardiopulmonary resuscitation (13.2% to 10.4%; p < 0.05), and intensive care unit admission (15.2% to 11.1%; p < 0.05) decreased during the study period, although no significant trend was noted in the number of emergency room visits. A steep increase was seen in inpatient hospice use in the last month of life (8.6% to 26.6%; p < 0.05), while downward trends were observed for hospice admission within three days prior to death (13.9% to 11%; p < 0.05). Patients were more likely to receive aggressive EoL care if they were younger, women, had treatment in tertiary hospitals, or had hematologic malignancies. In the subgroup analysis, the overall trend of aggressive EoL care decreased for all five major cancer types. CONCLUSION: The aggressiveness of EoL care in stage IV cancer patients showed an overall decrease during 2012-2018 in Korea.

Conjugated Block Copolymers for Functional Nanostructures.

Conjugated polymers have been actively studied as an alternative to inorganic semiconductors for their unique optical and electrical properties and low-cost solution processability. However, typical conjugated polymer films contain numerous defects that negatively affect their transport properties, which remains a major issue despite much effort to develop ways to improve the molecular packing structure. In principle, conjugated block copolymers (BCPs) composed of a rod-type conjugated polymer and a coil-type insulating polymer can assemble into various types of ordered nanostructures based on the microphase segregation of two polymer blocks. However, such assembly typically requires a relatively large volume fraction of the coil block or modification of the rod block, both of which tend to impede charge transport. As an alternative, we and others have fabricated nanoscale assemblies of conjugated BCPs via solution-phase self-assembly, which can be used as building blocks for construction of extended nanoarrays of conjugated polymers. In particular, BCPs containing poly(3-hexylthiophene) (P3HT), a conjugated polymer widely used for its high hole mobility, form highly ordered and technologically relevant one-dimensional (1D) nanowires with controlled lengths. A range of well-defined assembly structures such as square plates, ribbons, vesicles, and helices have been prepared from various conjugated BCPs, resembling those of peptide self-assembly, forming diverse nanostructures through combinations of π-π stacking, hydrogen bonding, and hydrophobic interactions.When the self-assembly of P3HT BCPs takes place at an air-water interface, the initially formed polymer nanowires further assemble into hierarchical two-dimensional (2D) nanoarrays with solvent evaporation. The fluidic nature of the water subphase allows fabrication of highly ordered assembly structures from P3HT BCPs with high P3HT content. The ultrathin free-standing film integrated in a field effect transistor (FET) showed orders of magnitude higher current and hole mobility compared to that fabricated by conventional spin-coating. Furthermore, binary self-assembly of a P3HT BCP and quantum dots (QDs) at the air-water interface generates well-ordered 2D films of alternating P3HT nanowires and 1D QD arrays. Unlike coil-coil BCP systems, QDs reside at the interface between P3HT and coil blocks for a broad range of QD sizes due to the strong P3HT packing interactions and the flexible water subphase, forming tight p-n junctions for enhanced photocurrent. Incorporation of magnetic nanoparticles can further improve the degree of order, enabling fabrication of long-range order and direction-controlled P3HT nanoarrays through magnetic-field induced self-assembly.The conjugated BCP approach is highly modular and can be combined with various types of functional molecules, polymers, and nanoparticles, offering a powerful platform for fabrication of functional polymer nanostructures with desired morphologies and properties. This Account introduces recent advances in the self-assembly of π-conjugated BCPs, describes how they differ from prototypical coil-coil type BCPs, and discusses current issues and future outlooks.

Oligonucleotides as Inhibitors of Ice Recrystallization.

Oligonucleotides of adenine (A20), guanine (G20), cytosine (C20), thymine (T20), cytosine-guanine ((CG)20), and adenine-thymine ((AT)20) were investigated as model compounds for ice recrystallization inhibition (IRI). Dehydroxy uracil (dU20), U20, and T20 were also compared to investigate the effect of minute changes in the hydrophobicity of the oligonucleotides on the IRI activity. Among the oligonucleotides considered in this study, T20 exhibited the best performance for IRI. In addition, the degree of polymerization of oligothymines varied over 5, 10, 20, 30, 50, and 100, and T20 was found to be the most effective for IRI. The IRI mechanism was investigated by comparing U20 and T20, which exhibited the lowest and highest IRI activity, respectively, among the oligonucleotides for their dynamic ice-shaping, thermal hysteresis, and ice nucleation inhibition. Little or no dynamic ice-shaping activity and small thermal hysteresis were observed for both nucleotides. All of the findings suggest that not the ice-polymer adhesion but the hydrophobic interactions of T20 in the interface layer might interfere with the water deposition on the ice crystal surfaces and contribute to the IRI activity of the T20 oligonucleotide.

Low-Molecular-Weight Fish Collagen Peptide (Valine-Glycine-Proline-Hydroxyproline-Glycine-Proline-Alanine-Glycine) Prevents Osteoarthritis Symptoms in Chondrocytes and Monoiodoacetate-Injected Rats.

The objective of this study was to investigate the effect of low-molecular-weight fish collagen (valine-glycine-proline-hydroxyproline-glycine-proline-alanine-glycine; LMWCP) on H2O2- or LPS-treated primary chondrocytes and monoiodoacetate (MIA)-induced osteoarthritis rat models. Our findings indicated that LMWCP treatment exhibited protective effects by preventing chondrocyte death and reducing matrix degradation in both H2O2-treated primary chondrocytes and cartilage tissue from MIA-induced osteoarthritis rats. This was achieved by increasing the levels of aggrecan, collagen type I, collagen type II, TIMP-1, and TIMP-3, while simultaneously decreasing catabolic factors such as phosphorylation of Smad, MMP-3, and MMP-13. Additionally, LMWCP treatment effectively suppressed the activation of inflammation and apoptosis pathways in both LPS-treated primary chondrocytes and cartilage tissue from MIA-induced osteoarthritis rats. These results suggest that LMWCP supplementation ameliorates the progression of osteoarthritis through its direct impact on inflammation and apoptosis in chondrocytes.

SH-PRO extract alleviates benign prostatic hyperplasia via ROS-mediated activation of PARP/caspase 3 and inhibition of FOXO3a/AR/PSA signaling in vitro and in vivo.

To target benign prostatic hyperplasia (BPH) as a common urinary disease in old men, in the current study, the antiproliferative and apoptotic mechanism of SH-PRO, a mixture of Angelica gigas and Astragalus membranaceus (2:1), was evaluated in BPH-1 cells and rats with testosterone-induced BPH. Herein, SH-PRO significantly reduced the viability of BPH-1 cells and dihydrotestosterone (DHT)-treated RWPE-1 cells. Also, SH-PRO increased the sub-G1 population in BPH-1 cells and consistently attenuated the expression of pro-PARP, pro-caspase 3, Bcl2, FOXO3a, androgen receptor (AR), and prostate-specific antigen (PSA) in BPH-1 cells and DHT-treated RWPE-1 cells. Of note, SH-PRO generated reactive oxygen species (ROS) in BPH-1 cells, while ROS inhibitor N-acetyl-l-cysteine (NAC) disturbed the ability of SH-PRO to reduce the expression of pro-PARP, FOXO3a, catalase, SOD, and increase sub-G1 population in BPH-1 cells. Furthermore, oral treatment of SH-PRO significantly abrogated the weight of the prostate in testosterone-treated rats compared to BPH control with the reduced expression of AR, PSA, and DHT and lower plasma levels of DTH, bFGF, and EGF with no toxicity. Overall, these findings highlight the antiproliferative and apoptotic potential of SH-PRO via ROS-mediated activation of PARP and caspase 3 and inhibition of FOXO3a/AR/PSA signaling as a potent anti-BPH candidate.

Correlating 3D Surface Atomic Structure and Catalytic Activities of Pt Nanocrystals.

Active sites and catalytic activity of heterogeneous catalysts is determined by their surface atomic structures. However, probing the surface structure at an atomic resolution is difficult, especially for solution ensembles of catalytic nanocrystals, which consist of heterogeneous particles with irregular shapes and surfaces. Here, we constructed 3D maps of the coordination number (CN) and generalized CN (CN_) for individual surface atoms of sub-3 nm Pt nanocrystals. Our results reveal that the synthesized Pt nanocrystals are enclosed by islands of atoms with nonuniform shapes that lead to complex surface structures, including a high ratio of low-coordination surface atoms, reduced domain size of low-index facets, and various types of exposed high-index facets. 3D maps of CN_ are directly correlated to catalytic activities assigned to individual surface atoms with distinct local coordination structures, which explains the origin of high catalytic performance of small Pt nanocrystals in important reactions such as oxygen reduction reactions and CO electro-oxidation.

Depletion of HNRNPA1 induces peroxisomal autophagy by regulating PEX1 expression.

Peroxisomes play an essential role in cellular homeostasis by regulating lipid metabolism and the conversion of reactive oxygen species (ROS). Several peroxisomal proteins, known as peroxins (PEXs), control peroxisome biogenesis and degradation. Various mutations in the PEX genes are genetic causes for the development of inheritable peroxisomal-biogenesis disorders, such as Zellweger syndrome. Among the peroxins, PEX1 defects are the most common mutations in Zellweger syndrome. PEX1 is an AAA-ATPase that regulates the recycling of PEX5, which is essential for importing peroxisome matrix proteins. However, the post-transcriptional regulation of PEX1 is largely unknown. Here, we showed that heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) controls PEX1 expression. In addition, we found that depletion of HNRNPA1 induces autophagic degradation of peroxisome, which is blocked in ATG5-knockout cells. In addition, depletion of HNRNPA1 increased peroxisomal ROS levels. Inhibition of the generation of peroxisomal ROS by treatment with NAC significantly suppressed pexophagy in HNRNPA1-deficient cells. Taken together, our results suggest that depletion of HNRNPA1 increases peroxisomal ROS and pexophagy by downregulating PEX1 expression.

Janus Nanosheets with Face-Selective Molecular Recognition Properties from DNA-Peptide Conjugates.

Chemical and functional anisotropy in Janus materials offer intriguing possibilities for constructing complex nanostructures and regulating chemical and biological reactions. Here, the authors report the fabrication of Janus nanosheets from molecular building blocks composed of two information-carrying biopolymers, DNA and peptides. Experimental and structural modeling studies reveal that DNA-peptide diblock conjugates assemble into Janus nanosheets with distinct DNA and peptide faces. The surprising level of structural control is attributed to the exclusive parallel ß-sheet formation of phenylalanine-rich peptides. This approach is extended to triblock DNA1-peptide-DNA2 conjugates, which assemble into nanosheets presenting two different DNA on opposite faces. The Janus nanosheets with independently addressable faces are utilized to organize an enzyme pair for concerted enzymatic reactions, where enhanced catalytic activities are observed. These results demonstrate that the predictable and designable peptide interaction is a promising tool for creating Janus nanostructures with regio-selective and sequence-specific molecular recognition properties.

Hypothermic Stem Cell Storage Using a Polypeptide Thermogel.

We report a polypeptide-based thermogel as a new tool for hypothermic storage of stem cells at ambient temperature (25 °C). Stem cells were suspended in the sol state (10 °C) of an aqueous poly(ethylene glycol)-poly(l-alanine) (PEG-PA) solution (4.0 wt %) in phosphate-buffered saline (PBS), which turned into a stem cell-incorporated gel by a heat-induced sol-to-gel transition. The cell harvesting procedure from the thermogels was simply performed through a gel-to-sol transition by diluting and cooling the system. More than 99% of stem cells died in PBS and Pluronic F127 thermogel (control thermogel) when the cells were stored at 25 °C for 7 days. The cell recovery rate from the PEG-PA thermogel (64%) was significantly greater than that from the commercially available HypoThermosol FRS preservation solution (HTS) (26%). Additionally, the surviving stem cells from the PEG-PA thermogel were healthier than those from HTS in terms of (1) expression of stemness biomarkers (NANOG, OCT4, and SOX2), (2) proliferation rate, and (3) differentiation potentials into osteogenic, chondrogenic, and adipogenic lineages. Membrane stabilization was suggested as a cell protection mechanism in the cytocompatible PEG-PA thermogel. The PEG-PA thermogel provides a convenient cytocompatible way for the storage and recovery of cells and thus is a promising tool for the transportation and short-term banking of cells.

Long-term impacts of appendectomy associated with increased incidence of inflammatory bowel disease, infection, and colorectal cancer.

PURPOSE: Although the appendix has been suggested to play a role in maintaining the gut microbiome and immune system, the ramifications of appendectomy on the development inflammatory bowel disease, sepsis, and colorectal cancer are yet to be determined. The purpose of this study was to evaluate the potential long-term impacts of appendectomy, with a focus on inflammatory bowel disease, infection, and colorectal cancer, using the National Healthcare Insurance Service (NHIS) database of Korea. METHODS: The National Healthcare Insurance Service database in Korea was used for analysis. Adult patients who received appendectomy between 2005 and 2013 were identified. The control group consisted of patients who did not receive appendectomy were matched by baseline characteristics including comorbidities and frequency of healthcare resource utilization. The primary outcome was the incidence-rate ratio (IRR) of Crohn's disease, ulcerative colitis, Clostridium difficile infection, sepsis, and colorectal cancer after appendectomy or the index date. RESULTS: We identified 914,208 patients who underwent appendectomy, and after matching with control patients, a total of 486,844 patients were included for analysis. Patients who underwent appendectomy showed a significantly higher incidence of Crohn's disease (IRR 4.40, 95% confidence interval (CI) 3.78-5.13) and ulcerative colitis (IRR 1.78, 95% CI 1.63-1.93) compared to the control group during the 5-year follow-up period. The associations between appendectomy and Clostridium difficile infection, sepsis, and colorectal cancer were all found to be significant. CONCLUSION: Patients who underwent appendectomy may be at increased risk for developing Crohn's disease, ulcerative colitis, Clostridium difficile infection, sepsis, and colorectal cancer.

Association between continuous deep sedation and survival time in terminally ill cancer patients.

PURPOSE: Our study aimed to evaluate the association between CDS and survival time using the likelihood of receiving CDS to select a matched non-CDS group through an accurate measurement of survival time based on initiation of CDS. METHODS: A retrospective cohort study was performed using an electronic database to collect data regarding terminally ill cancer patients admitted to a specialized palliative care unit from January 2012 to December 2016. We first used a Cox proportional hazard model with receiving CDS as the outcome to identify individuals with the highest plausibility of receiving CDS among the non-CDS group (n = 663). We then performed a multiple regression analysis comparing the CDS group (n = 311) and weighted non-CDS group (n = 311), using initiation of CDS (actual for the CDS group; estimated for the non-CDS group) as the starting time-point for measuring survival time. RESULTS: Approximately 32% of participants received CDS. The most common indications were delirium or agitation (58.2%), intractable pain (28.9%), and dyspnea (10.6%). Final multiple regression analysis revealed that survival time was longer in the CDS group than in the non-CDS group (Exp(ß), 1.41; P < 0.001). Longer survival with CDS was more prominent in females, patients with renal dysfunction, and individuals with low C-reactive protein (CRP) or ferritin, compared with their counterpart subgroup. CONCLUSIONS: CDS was not associated with shortened survival; instead, it was associated with longer survival in our terminally ill cancer patients. Further studies in other populations are required to confirm or refute these findings.

Paediatric palliative screening scale as a useful tool for clinicians' assessment of palliative care needs of pediatric patients: a retrospective cohort study.

BACKGROUND: Although the importance of palliative care in pediatric patients has been emphasized, many health care providers have difficulty determining when patients should be referred to the palliative care team. The Paediatric Palliative Screening Scale (PaPaS) was developed as a tool for screening pediatric patients for palliative care needs. The study aimed to evaluate the PaPaS as a reliable tool for primary care clinicians unfamiliar with palliative care. METHODS: This was a retrospective cohort study of patients referred to the pediatric palliative care teams in two tertiary hospitals in the Republic of Korea between July 2018 and October 2019. RESULTS: The primary clinical and pediatric palliative care teams assessed the PaPaS scores of 109 patients, and both teams reported a good agreement for the sum of the PaPaS score. Furthermore, the PaPaS scores correlated with those obtained using the Lansky performance scale. Although the mean PaPaS score was higher in the pediatric palliative care team, the scores were higher than the cut-off score for referral in both groups. CONCLUSION: The PaPaS can be a useful tool for primary care clinicians to assess the palliative care needs of patients and their families.

Synthesis and Single-Particle Surface-Enhanced Raman Scattering Study of Plasmonic Tripod Nanoframes with Y-Shaped Hot-Zones.

Herein, plasmonic metal tripod nanoframes with three-fold symmetry were synthesized in a high yield (∼83%), and their electric field distribution and single-particle surface-enhanced Raman scattering (SERS) were studied. We realized such complex frame morphology by synthesizing analogous tripod nanoframes through multiple transformations. The precise control of the Au growth pattern led to uniform tripod nanoframes embedded with circle or line-shaped hot spots. The linear-shaped nanogaps ("Y"-shaped hot-zone) of the frame structures can strongly and efficiently confine the electric field, allowing for strong SERS signals. Coupled with a high synthetic yield of the targeted frame structure, strong and uniform SERS signals were obtained inside the nanoframe gaps. Remarkably, quite reproducible SERS signals were obtained with these structures-the SERS enhancement factors with an average value of 7.9 × 107 with a distribution of enhancement factors from 2.2 × 107 to 2.2 × 108 for 45 measured individual particles.

Single chain in mean field simulation of flexible and semiflexible polymers: comparison with discrete chain self-consistent field theory.

Single chain in mean field (SCMF) simulation is a theoretical framework performing Monte Carlo moves of explicit polymer chains under quasi-instantaneously updated external fields which were originally imported from the self-consistent field theory (SCFT). Even though functional-based hybrid simulations are often used to compare the results of SCFT and MC simulation, the adoption of a finite number of coarse-grained segments makes direct comparison rather difficult. In this study, we perform SCMF simulation of block copolymers using various chain models and quantitatively compare it with discrete chain SCFT (DCSCFT) which finds the mean field solution of polymers with a finite number of segments. By comparing free energy and natural period of the symmetric block copolymer lamellar phase, we systematically show that DCSCFT serves as an intermediate step between SCMF simulation and SCFT. In addition, by adopting angle dependent bond potential, we perform SCMF simulation of semiflexible polymers using bead-spring and freely jointed chain models. As the chain stiffness increases, the lamellar phase tends to align perpendicular to the surfaces when confined between two neutral walls. We also investigate the effects of fluctuation and chain stiffness on the distribution of chain ends. The tendency of chain end segregation towards the surfaces turns out to increase as the chain stiffness increases for both homopolymer and block copolymer systems.

Effectiveness of home hospice care: a nationwide prospective observational study.

PURPOSE: Many assert the need for home hospice care. However, limited research has shown its effectiveness. The authors of this study thus evaluated the effectiveness of a home hospice care pilot project regarding (1) early enrollment in hospice care, (2) efficient use of inpatient hospice resources, and (3) enabling terminally ill patients to stay at their preferred place of care. METHODS: The authors conducted a nationwide prospective observational study. Patients were divided into home hospice care users (ever-users, n = 902) and inpatient-only hospice care users (never-users, n = 8210). Information about hospice service utilization was collected from a web-based registry system. Patients were registered if they started to receive the hospice service after providing written informed consent during the pilot project from March 2016-July 2017. RESULTS: Most ever-users preferred to stay at home (84.0%), while never-users preferred hospital admission (66.9%). Most ever-users were enrolled in hospice by home care (78.9%) and used both home and inpatient care (72.4%). The overall duration of hospice care was significantly longer among ever-users than never-users (median 39 vs. 15 days, respectively; mean ± SD 59.6 ± 62.8 vs. 24.8 ± 32.1, respectively; p < .001). Participation in the pilot program improved bed utilization (p = .025) and turnover rate (p < .001) of inpatient hospice service. CONCLUSIONS: Home hospice care enabled early enrollment in hospice services and provided a valid option to patients who wished to stay at home. Policy efforts to facilitate home hospice care are needed.

Synthesis, biological evaluation and molecular modelling of 2,4-disubstituted-5-(6-alkylpyridin-2-yl)-1H-imidazoles as ALK5 inhibitors.

A series of 2,4-disubstituted-5-(6-alkylpyridin-2-yl)-1H-imidazoles, 7a-c, 11a-h, and 16a-h has been synthesised and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. Incorporation of a quinoxalin-6-yl moiety and a methylene linker at the 4- and 2-position of the imidazole ring, respectively, and a m-CONH2 substituent in the phenyl ring generated a highly potent and selective ALK5 inhibitor 11e. Docking model of ALK5 in complex with 11e showed that it fitted well in the ATP-binding pocket with favourable interactions.

LC-MS/MS analysis of puerarin and 18ß-glycyrrhetinic acid in human plasma after oral administration of Samso-eum and its application to pharmacokinetic study.

The aim of this study was to confirm pharmacokinetic screening of multiple components in healthy Korean subjects after oral administration of Samso-eum and perform quantitation of active components in the human plasma. Thirteen potential bioactive components [puerarin (PRR), daidzin, nodakenin, ginsenoside Rb1, 18ß-glycyrrhetinic acid (18ß-GTA), 6-shogaol, naringin, glycyrrhizin, hesperidin, platycodin D, naringenin, hesperetin, and 6-gingerol] were screened based on literature. The results showed that three analytes (daidzin, naringenin, and hesperetin) were detected in trace amounts. In addition, PRR and 18ß-GTA were detected in human plasma after the oral administration of Samso-eum. In this study, a liquid chromatography-electrospray ionization-tandem mass spectrometry method was validated for the simultaneous determination of PRR and 18ß-GTA in human plasma. This was the first study to evaluate pharmacokinetics of PRR and 18ß-GTA after the usual oral dose of Samso-eum (30 g containing 102.48 mg PRR, 48.18 mg glycyrrhizin) in human subjects.

QSAR Model for Predicting the Cannabinoid Receptor 1 Binding Affinity and Dependence Potential of Synthetic Cannabinoids.

In recent years, there have been frequent reports on the adverse effects of synthetic cannabinoid (SC) abuse. SCs cause psychoactive effects, similar to those caused by marijuana, by binding and activating cannabinoid receptor 1 (CB1R) in the central nervous system. The aim of this study was to establish a reliable quantitative structure-activity relationship (QSAR) model to correlate the structures and physicochemical properties of various SCs with their CB1R-binding affinities. We prepared tetrahydrocannabinol (THC) and 14 SCs and their derivatives (naphthoylindoles, naphthoylnaphthalenes, benzoylindoles, and cyclohexylphenols) and determined their binding affinity to CB1R, which is known as a dependence-related target. We calculated the molecular descriptors for dataset compounds using an R/CDK (R package integrated with CDK, version 3.5.0) toolkit to build QSAR regression models. These models were established, and statistical evaluations were performed using the mlr and plsr packages in R software. The most reliable QSAR model was obtained from the partial least squares regression method via Y-randomization test and external validation. This model can be applied in vivo to predict the addictive properties of illicit new SCs. Using a limited number of dataset compounds and our own experimental activity data, we built a QSAR model for SCs with good predictability. This QSAR modeling approach provides a novel strategy for establishing an efficient tool to predict the abuse potential of various SCs and to control their illicit use.