Phosphorylation of hTERT at threonine 249 is a novel tumor biomarker of aggressive cancer with poor prognosis in multiple organs.

Recent evidence indicates that RNA-dependent RNA polymerase (RdRP) activity of human telomerase reverse transcriptase (hTERT) regulates expression of target genes and is directly involved in tumor formation in a telomere-independent manner. Non-canonical function of hTERT has been considered as a therapeutic target for cancer therapy. We have previously shown that hTERT phosphorylation at threonine 249 (p-hTERT), which promotes RdRP activity, is an indicator of an aggressive phenotype and poor prognosis in liver and pancreatic cancers, using two cohorts with small sample sizes with polyclonal p-hTERT antibody. To clarify the clinical relevance of p-hTERT, we developed a specific monoclonal antibody and determined the diagnostic and prognostic value of p-hTERT in cancer specimens using a large cohort. A monoclonal antibody for phosphorylated hTERT (p-hTERT) at threonine 249 was developed and validated. The antibody was used for the immunohistochemical staining of formalin-fixed, paraffin-embedded specimens from 1523 cases of lung, colon, stomach, pancreatic, liver, breast, and kidney cancers. We detected elevated p-hTERT expression levels in cases with a high mitotic activity, high pathological grade, and high nuclear pleomorphism. Elevated p-hTERT expression was an independent prognostic factor for lung, pancreatic, and liver cancers. Furthermore, p-hTERT expression was associated with immature and aggressive features, such as adenosquamous carcinoma (lung and pancreas), invasive type of cancer (lung), high serum alpha-fetoprotein level (liver), and triple-negative status (breast). In conclusion, RdRP activity indicated by p-hTERT expression predicts aggressive cancer phenotypes in various types of cancer. Thus, p-hTERT is a novel biomarker for the diagnosis of aggressive cancers with a poor prognosis. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Prostaglandin E2-Induced Immune Exhaustion and Enhancement of Antiviral Effects by Anti-PD-L1 Antibody Combined with COX-2 Inhibitor in Bovine Leukemia Virus Infection.

Bovine leukemia virus (BLV) infection is a chronic viral infection of cattle and endemic in many countries, including Japan. Our previous study demonstrated that PGE2, a product of cyclooxygenase (COX) 2, suppresses Th1 responses in cattle and contributes to the progression of Johne disease, a chronic bacterial infection in cattle. However, little information is available on the association of PGE2 with chronic viral infection. Thus, we analyzed the changes in plasma PGE2 concentration during BLV infection and its effects on proviral load, viral gene transcription, Th1 responses, and disease progression. Both COX2 expression by PBMCs and plasma PGE2 concentration were higher in the infected cattle compared with uninfected cattle, and plasma PGE2 concentration was positively correlated with the proviral load. BLV Ag exposure also directly enhanced PGE2 production by PBMCs. Transcription of BLV genes was activated via PGE2 receptors EP2 and EP4, further suggesting that PGE2 contributes to disease progression. In contrast, inhibition of PGE2 production using a COX-2 inhibitor activated BLV-specific Th1 responses in vitro, as evidenced by enhanced T cell proliferation and Th1 cytokine production, and reduced BLV proviral load in vivo. Combined treatment with the COX-2 inhibitor meloxicam and anti-programmed death-ligand 1 Ab significantly reduced the BLV proviral load, suggesting a potential as a novel control method against BLV infection. Further studies using a larger number of animals are required to support the efficacy of this treatment for clinical application.

Cation-π Interactions in Organic Synthesis.

The cation-π interaction is an attractive noncovalent interaction between a cation and a π system. Due to the stronger interaction energy than those of the other π interactions, such as π-π and CH-π interactions, the cation-π interaction has recently been recognized as a new tool for controlling the regio- and stereoselectivities in various types of organic reactions. This review attempts to cover a variety of organic reactions controlled by cation-π interactions, which includes not only recent examples but also those reported before the term "cation-π interaction" was defined in 1990. This review will provide comprehensive knowledge on the role of cation-π interactions in organic synthesis.

[Intractable Atrial Arrhythmia after Maze Procedure].

Maze procedure has achieved high cure rates and become the surgical golden standard for the treatment of atrial fibrillation. But, atrial arrhythmia after maze procedure is often persistent and drug-resistant. In these cases, diagnosis by electrophysiological study (EPS) and treatment by catheter ablation (ABL) are useful. In our hospital, maze procedure has been actively performed for mitral valve surgery with atrial arrhythmia. We examined the cases that required ABL after maze procedure in our hospital. We reported 2 such typical cases where ablation of cavo-tricuspid isthmus line (CTI) in the right atrium and left superior pulmonary vein-left atrial appendage space( LSPV-LAA ridge) in the left atrium was effective.

Amphiprotism-Coupled Near-Infrared Emission in Extended Pyrazinacenes Containing Seven Linearly Fused Pyrazine Units.

Peripherally substituted tetradecaazaheptacene (N14Hp) compounds, exhibiting amphiprotism-coupled emission, have been synthesized. X-ray crystallography reveals a planar acene-like chromophore, and electronic absorption and emission occur in the near-infrared biological transparency window (650-900 nm). The compounds exhibit long-wavelength emission with photoluminescence quantum yields ΦPL up to ∼0.61 at 686 nm, with the monodeprotonated state ΦPL ≈ 0.58 at 712 nm. This unprecedented highly nitrogenous chromophore illustrates the stability and utility of the pyrazinacenes for different applications based on their photophysical properties and chemical structures.

Aqueous Lubrication with the Molecularly Confined Films of Silicone-Based Amphiphilic Block Copolymer Aggregates.

The confined film structures and tribological properties of the dilute aqueous solution of a silicone-based amphiphilic block copolymer, bis-isobutyl poly(ethylene glycol) (PEG)-14/amodimethicone (BIPA) copolymer, between mica surfaces were investigated. The BIPA copolymer existed as positively charged water-soluble aggregates in the solution. The adsorption behavior of the BIPA copolymer aggregates on a mica surface from solution was studied using an atomic force microscope (AFM); the result showed the immediate formation of a uniform adsorbed BIPA copolymer layer, followed by the gradual deposition of BIPA aggregates on the top of the adsorbed layer. Friction measurements were carried out using the surface forces apparatus (SFA) for the confined films of BIPA copolymer solution between mica surfaces, which revealed two different sliding film structures depending on the elapsed time after surface preparation. The sliding film consisting of two adsorbed BIPA copolymer layers was obtained for a relatively short elapsed time (not longer than 3 h), which had an extremely low friction coefficient µ (of the order of 10-5). The sliding film on the following day (elapsed time of approximately 24 h) had the structure of a deposited/kinetically trapped BIPA aggregate layer confined between the opposing adsorbed layers, and the µ values were within the range from 10-4 to 10-3. Our results suggest that the different elapsed time ranges and resulting absence or presence of the intervening layer of trapped aggregates between the absorbed layers determine the tribological properties of the confined films. Molecular friction mechanisms are discussed for the two sliding structures, which give insight into using amphiphilic block copolymer aggregates for a new class of aqueous lubrication system to design extremely low friction interfaces.

[Severe Coronary Artery Spasm after Coronary Artery Bypass Grafting;Report of a Case].

Coronary artery spasm after coronary artery bypass grafting(CABG) is rare and often fatal. There is no established treatment for perioperative coronary spasm because of the rare and not fully understood complications. We report a 67-year-old male, who experienced perioperative spasm of native coronary arteries and the left thoracic artery graft following CABG. Several transcatheter intracoronary injections of isosorbide sulfate failed to relieve the spasm completely. After 5 days' circulatory support with intra-aortic balloon pumping, the cardiac function improved and the patient recovered. Echocardiography performed before discharge showed decreased left ventricular systolic function with apical akinesis. Postoperative coronary angiography revealed 4 of the 5 grafts were patent.

Prostaglandin E2 Induction Suppresses the Th1 Immune Responses in Cattle with Johne's Disease.

Johne's disease, caused by Mycobacterium avium subsp. paratuberculosis, is a bovine chronic infection that is endemic in Japan and many other countries. The expression of immunoinhibitory molecules is upregulated in cattle with Johne's disease, but the mechanism of immunosuppression is poorly understood. Prostaglandin E2 (PGE2) is immunosuppressive in humans, but few veterinary data are available. In this study, functional and kinetic analyses of PGE2 were performed to investigate the immunosuppressive effect of PGE2 during Johne's disease. In vitro PGE2 treatment decreased T-cell proliferation and Th1 cytokine production and upregulated the expression of immunoinhibitory molecules such as interleukin-10 and programmed death ligand 1 (PD-L1) in peripheral blood mononuclear cells (PBMCs) from healthy cattle. PGE2 was upregulated in sera and intestinal lesions of cattle with Johne's disease. In vitro stimulation with Johnin purified protein derivative (J-PPD) induced cyclooxygenase-2 (COX-2) transcription, PGE2 production, and upregulation of PD-L1 and immunoinhibitory receptors in PBMCs from cattle infected with M. avium subsp. paratuberculosis Therefore, Johnin-specific Th1 responses could be limited by the PGE2 pathway in cattle. In contrast, downregulation of PGE2 with a COX-2 inhibitor promoted J-PPD-stimulated CD8+ T-cell proliferation and Th1 cytokine production in PBMCs from the experimentally infected cattle. PD-L1 blockade induced J-PPD-stimulated CD8+ T-cell proliferation and interferon gamma production in vitro Combined treatment with a COX-2 inhibitor and anti-PD-L1 antibodies enhanced J-PPD-stimulated CD8+ T-cell proliferation in vitro, suggesting that the blockade of both pathways is a potential therapeutic strategy to control Johne's disease. The effects of COX-2 inhibition warrant further study as a novel treatment of Johne's disease.

Cooperation of PD-1 and LAG-3 in the exhaustion of CD4+ and CD8+ T cells during bovine leukemia virus infection.

Bovine leukemia virus (BLV) is a retrovirus that infects B cells in cattle and causes bovine leukosis after a long latent period. Progressive exhaustion of T cell functions is considered to facilitate disease progression of BLV infection. Programmed death-1 (PD-1) and lymphocyte activation gene-3 (LAG-3) are immunoinhibitory receptors that contribute to T-cell exhaustion caused by BLV infection in cattle. However, it is unclear whether the cooperation of PD-1 and LAG-3 accelerates disease progression of BLV infection. In this study, multi-color flow cytometric analyses of PD-1- and LAG-3-expressing T cells were performed in BLV-infected cattle at different stages of the disease. The frequencies of PD-1+LAG-3+ heavily exhausted T cells among CD4+ and CD8+ T cells was higher in the blood of cattle with B-cell lymphoma over that of BLV-uninfected and BLV-infected cattle without lymphoma. In addition, blockade assays of peripheral blood mononuclear cells were performed to examine whether inhibition of the interactions between PD-1 and LAG-3 and their ligands by blocking antibodies could restore T-cell function during BLV infection. Single or dual blockade of the PD-1 and LAG-3 pathways reactivated the production of Th1 cytokines, interferon-γ and tumor necrosis factor-α, from BLV-specific T cells of the infected cattle. Taken together, these results indicate that PD-1 and LAG-3 cooperatively mediate the functional exhaustion of CD4+ and CD8+ T cells and are associated with the development of B-cell lymphoma in BLV-infected cattle.

[2 + 2] Photodimerization of Naphthylvinylpyridines through Cation-π Interactions in Acidic Solution.

Irradiation of (E)-4-(2-(2-naphthyl)vinyl)pyridine (1a) and (E)-4-(2-(1-naphthyl)vinyl)pyridine (1b) with a 250 W high-pressure mercury lamp in acidic solution afforded synHT dimers in high stereoselectivities. Similar results were obtained by visible light irradiation. On the other hand, when the reactions were carried out under neutral conditions, the stereoselectivities were very low, and the yields were decreased by visible light irradiation. Comparison of the UV-vis spectra between the acidic and the neutral conditions elucidated that the red shift was observed in acidic solutions. These results show that HCl plays essential roles not only in the preorientation of substrates through cation-π interactions, but also in the changes in the absorption properties of substrates that enable visible light reactions.

[Fifteen-year Follow-up of a Patient with Aortitis, Treated by Sino-tubular Junction Plication Using a Prosthetic Tube Graft for Aortic Regurgitation;Report of a Case].

A 43-year-old woman was diagnosed with aortitis associated with mild aortic regurgitation (AR) at the age of 25, which advanced to a severe grade requiring surgical treatment at age 28. Dilation of the sinotubular junction (STJ) was treated with ascending aortic replacement (Hemashield Gold 24 mm), which reduced AR from severe to mild. The patient conceived 9 years later and delivered a baby by cesarean section at 38 weeks of gestation. By appropriate control of inflammation with steroid, neither deterioration of the aortic valve nor cardiac function has been noted during the 15 years of follow-up after surgery.

Synthesis of Molecular Seesaw Balances and the Evaluation of Pyridinium-π Interactions.

A series of molecular seesaw balances 1-5 have been developed to measure the relative strength of pyridinium-π (cation-π) interactions. The cycloaddition of 1-azaanthracene and o-quinodimethane under microwave irradiation afforded the efficient synthesis of 1 and 5. Introduction of substituents to the pyridine ring of balance 1 was achieved to produce 2-4 in good yields. Anion exchange of 1·MeI afforded 1·MeX with a variety of counteranions (X = Cl, Br, I, BF4, PF6, OAc). These balances adopt two distinct conformers, A and B, which are stabilized by a cation-π interaction and a π-π interaction, respectively. The conformer ratio was determined on the basis of the observed averaged 3J coupling constants for H1-C-C-H2 by comparison with the boundary JA and JB values, which were estimated by applying the Carplus-Altona equation to the dihedral angles of the optimized conformers A and B. The effects of the solvent, substituent and counteranion on the ΔG values were elucidated using these molecular balances. Thermodynamic parameters obtained from a van't Hoff plot as well as the electrostatic potential maps for both conformers A and B of the molecular balances helped us to better understand the obtained results.

Toward the treatment for Alzheimer's disease: adsorption is primary mechanism of removing amyloid ß protein with hollow-fiber dialyzers of the suitable materials, polysulfone and polymethyl methacrylate.

The accumulation of amyloid ß protein (Aß) in the brain reflects cognitive impairment in Alzheimer's disease. We hypothesized that the rapid removal of Aß from the blood by an extracorporeal system may act as a peripheral Aß sink from the brain. The present study aimed to determine the optimal materials and modality for Aß removal by hemodialyzers. In a batch analysis, hollow-fiber fragments of polysulfone (PSf) and polymethyl methacrylate (PMMA) showed greater removal efficiency of Aß than did other materials, such as cellulose-triacetates and ethylene-vinyl alcohol copolymer (PSf:PMMA at 30 min, 98.6 ± 2.4 %:97.8 ± 0.4 % for Aß1-40 and 96.6 ± 0.3 %:99.0 ± 1.0 % for Aß1-42). In a modality study, the Aß solution was applied to PSf dialyzers and circulated in the dialysis and Air-filled adsorption-mode (i.e., the outer space of the hollow fibers was filled with air) or phosphate-buffered saline (PBS)-filled adsorption modes. The Aß1-40 removal efficiency of the pre/post dialyzer in the Air-filled adsorption-mode was the highest (62.4 ± 12.6 %, p = 0.007). In a flow rate study in the Air-filled adsorption-mode, 200 mL/min showed the highest Aß1-40 reduction rate of pool solution (97.3 ± 0.8 % at 15 min) compared with 20 mL/min (p = 0.00001) and 50 mL/min (p = 0.00382). PMMA dialyzers showed similar high reduction rates. Thus, the optimal modality for Aß removal was the adsorption-mode with PSf or PMMA hollow fibers at around 50 mL/min flow rate, which seems to be suitable for clinical use.

[Incomplete Surgical Resection of a Right Ventricular Hemangioma with Asymptomatic Gradual Enlargement for more than a Decade;Report of a Case].

We encountered a case of a cardiac hemangioma protruding into the inner cavity of the right ventricle from the right ventricular free wall. The tumor gradually enlarged over 11 years (from 35 mm to 78mm) without presenting any symptoms. However, when it extended to the right ventricular outflow tract, non-sustained ventricular tachycardia occurred, and emergency surgery was required. The tumor was diagnosed as a cavernous benign hemangioma. Complete resection was not possible, and the part involving the right ventricle remained. This residual tumor caused postoperative ventricular arrhythmia, and an implantable cardioverter defibrillator was required. We concluded that non-surgically treated cardiac hemangiomas carry the risk of non-resectability, regardless of malignancy.

Low-Friction Adsorbed Layers of a Triblock Copolymer Additive in Oil-Based Lubrication.

The tribological properties of the dilute solution of an ABA triblock copolymer, poly(11-acrylamidoundecanoic acid)-block-poly(stearyl methacrylate)-block-poly(11-acrylamidoundecanoic acid (A5S992A5), in poly(α-olefin) (PAO) confined between mica surfaces were investigated using the surface forces apparatus (SFA). Friction force was measured as a function of applied load and sliding velocity, and the film thickness and contact geometry during sliding were analyzed using the fringes of equal chromatic order (FECO) in the SFA. The results were contrasted with those of confined PAO films; the effects of the addition of A5S992A5 on the tribological properties were discussed. The thickness of the A5S992A5/PAO system varied with time after surface preparation and with repetitive sliding motions. The thickness was within the range from 40 to 70 nm 1 day after preparation (the Day1 film), and was about 20 nm on the following day (the Day2 film). The thickness of the confined PAO film was thinner than 1.4 nm, indicating that the A5S992A5/PAO system formed thick adsorbed layers on mica surfaces. The friction coefficient was about 0.03 to 0.04 for the Day1 film and well below 0.01 for the Day2 film, which were 1 or 2 orders of magnitude lower than the values for the confined PAO films. The time dependent changes of the adsorbed layer thickness and friction properties should be caused by the relatively low solubility of A5S992A5 in PAO. The detailed analysis of the contact geometry and friction behaviors implies that the particularly low friction of the Day2 film originates from the following factors: (i) shrinkage of the A5S992A5 molecules (mainly the poly(stearyl methacrylate) blocks) that leads to a viscoelastic properties of the adsorbed layers; and (ii) the intervening PAO layer between the adsorbed polymer layers that constitutes a high-fluidity sliding interface. Our results suggest that the block copolymer having relatively low solubility in a lubricant base oil is effective at forming low-friction adsorbed layers in oil-based lubrication.

Isolation, identification, and formation conditions of a novel Maillard yellowish pigment, pyrrolothiazolate.

We isolated a novel yellow pigment from a model Maillard reaction system containing l-cysteine, l-lysine, and glucose and identified it as 6-hydroxy-3[R],7a[S]-dimethyl-7-oxo-2,3-dihydropyrrolo[2,1-b]thiazole-3-calboxylic acid. This compound was a novel pyrrolothiazole derivative carrying a carboxy group and was named pyrrolothiazolate. This compound showed the absorption maxima at 300 and 360 nm under acidic and neutral conditions, while 320 and 400 nm did under alkaline conditions. Pyrrolothiazolate formed from cysteine and glucose was the major low-molecular-weight Maillard pigment in the reaction mixture, and its formation was stimulated by adding lysine to the reaction cocktail. After heating at 110 °C for 2 h, 1-2 mg/mL of pyrrolothiazolate was formed in a reaction mixture containing 100 mM cysteine, 200 mM lysine, and 300 mM glucose dissolved in 0.5 m acetate buffer (pH 6.0) or 0.5 m phosphate buffer (pH 6.5).

Serum bta-miRNA-375 as a potential biomarker for the early diagnosis of enzootic bovine leukosis.

To identify a biomarker for the early diagnosis of enzootic bovine leukosis (EBL) caused by bovine leukemia virus (BLV), we investigated the expression of a microRNA, bta-miR-375, in cattle serum. Using quantitative reverse-transcriptase PCR analysis, we measured bta-miR-375 levels in 27 samples from cattle with EBL (EBL cattle), 45 samples from animals infected with BLV but showing no clinical signs (NS cattle), and 30 samples from cattle uninfected with BLV (BLV negative cattle). In this study, we also compared the kinetics of bta-miR-375 with those of the conventional biomarkers of proviral load (PVL), lactate dehydrogenase (LDH), and thymidine kinase (TK) from the no-clinical-sign phase until EBL onset in three BLV-infected Japanese black (JB) cattle. Bta-miR-375 expression was higher in NS cattle than in BLV negative cattle (P < 0.05) and greater in EBL cattle than in BLV negative and NS cattle (P < 0.0001 for both comparisons). Receiver operating characteristic curves demonstrated that bta-miR-375 levels distinguished EBL cattle from NS cattle with high sensitivity and specificity. In NS cattle, bta-miR-375 expression was increased as early as at 2 months before EBL onset-earlier than the expression of PVL, TK, or LDH isoenzymes 2 and 3. These results suggest that serum miR-375 is a promising biomarker for the early diagnosis of EBL.

Molecular characterization of feline immune checkpoint molecules and establishment of PD-L1 immunohistochemistry for feline tumors.

Spontaneous tumors are a major cause of death in cats. Treatment of human tumors has progressed dramatically in the past decade, partly due to the success of immunotherapies using immune checkpoint inhibitors, such as anti-programmed death 1 (PD-1) and anti-PD-ligand 1 (PD-L1) antibodies. However, little is known about the PD-1 pathway and its association with tumor disease in cats. This study investigated the applicability of anti-PD-1/PD-L1 therapy in feline tumors. We first determined the complete coding sequence of feline PD-L1 and PD-L2, and found that the deduced amino acid sequences of feline PD-L1/PD-L2 share high sequence identities (66-83%) with orthologs in other mammalian species. We prepared recombinant feline PD-1, PD-L1, and PD-L2 proteins and confirmed receptor-ligand binding between PD-1 and PD-L1/PD-L2 using flow cytometry. Next, we established an anti-feline PD-L1 monoclonal antibody (clone CL1Mab-7) to analyze the expression of PD-L1. Flow cytometry using CL1Mab-7 revealed the cell surface expression of PD-L1 in a feline macrophage (Fcwf-4) and five mammary adenocarcinoma cell lines (FKNp, FMCm, FYMp, FONp, and FONm), and showed that PD-L1 expression was upregulated by interferon-γ stimulation. Finally, immunohistochemistry using CL1Mab-7 also showed PD-L1 expression in feline squamous cell carcinoma (5/5, 100%), mammary adenocarcinoma (4/5, 80%), fibrosarcoma (5/5, 100%), and renal cell carcinoma (2/2, 100%) tissues. Our results strongly encourage further investigations of the PD-1/PD-L1 pathway as a potential therapeutic target for feline tumors.

Aging and stiction dynamics in confined films of a star polymer melt.

The stiction properties of a star polyisoprene (PIP) melt (having 22 arms and an arm molecular weight of around 5000, M(w) ≈ 110,000) confined between mica surfaces were investigated using the surface forces apparatus. Stop-start experiments were carried out and the stiction spike was measured as a function of surface stopping (aging) time t and applied pressure P; the time constants of the phase transitions in the stiction dynamics (freezing on stopping and melting on starting) were obtained from the force relaxation behaviors. The results were compared with those of a confined linear-PIP melt (M(w) ≈ 48,000) and other confined fluid systems; the effect of star architecture on the phase transitions in confinement during aging is discussed. Estimation of the molecular size gives that the confined star-PIP films consist of three molecular layers; a non-adsorbed layer sandwiched between two layers adsorbed on opposed mica surfaces. There are (at least) four time constants in the freezing transition of the confined star-PIP melt; fast (τ(1)) and slow (τ(2)) time constants for lateral force relaxation on stopping, critical aging time for freezing (τ(f)), and the logarithmic increase of the spike height against t. The three time constants on stopping, τ(1), τ(2), and τ(f), increase with the increase of P (decrease of the thickness D). As regards the melting transition on starting, spike force decay was fitted by a single exponential function and one time constant was obtained, which is insensitive to P (D). Comparison of the time constants between freezing and melting, and also with the results of linear-PIP reveals that the stiction dynamics of the star-PIP system involves the relaxation and rearrangement of segmental-level and whole molecular motions. Lateral force relaxation on stopping is governed by the individual and cooperative rearrangements of local PIP segments and chain ends of the star, which do not directly lead to the freezing of the system. Instead, geometrical rearrangements of the soft star-PIP spheres into dense packing between surfaces (analogous to the concept of a colloidal glass transition) are the major mechanism of the freezing transition (stiction) after aging. Interdigitation of PIP segments/chain ends between neighboring star molecules also contributes to the spike growth along with aging, and the melting transition on starting.

Contribution of cation-π interactions in iminium catalysis.

Ab initio calculations were carried out for a benzyl-substituted iminium cation derived from (E)-crotonaldehyde and a chiral imidazolidinone that was developed as an organocatalyst by MacMillan et al. At the MP2 level of theory it is predicted that the phenyl group is close to the iminium moiety in the most stable conformer, suggesting that the cation-π interaction contributes to the stabilization of this conformer. Energy decomposition analyses on model systems indicate that the electrostatic and polarization terms make significant contribution to the attractive interactions between the benzene ring and the iminium cation.