Coordinated demethylation of H3K9 and H3K27 is required for rapid inflammatory responses of endothelial cells.

Histone H3 lysine-9 di-methylation (H3K9me2) and lysine-27 tri-methylation (H3K27me3) are linked to repression of gene expression, but the functions of repressive histone methylation dynamics during inflammatory responses remain enigmatic. Here, we report that lysine demethylases 7A (KDM7A) and 6A (UTX) play crucial roles in tumor necrosis factor (TNF)-α signaling in endothelial cells (ECs), where they are regulated by a novel TNF-α-responsive microRNA, miR-3679-5p. TNF-α rapidly induces co-occupancy of KDM7A and UTX at nuclear factor kappa-B (NF-κB)-associated elements in human ECs. KDM7A and UTX demethylate H3K9me2 and H3K27me3, respectively, and are both required for activation of NF-κB-dependent inflammatory genes. Chromosome conformation capture-based methods furthermore uncover increased interactions between TNF-α-induced super enhancers at NF-κB-relevant loci, coinciding with KDM7A and UTX recruitments. Simultaneous pharmacological inhibition of KDM7A and UTX significantly reduces leukocyte adhesion in mice, establishing the biological and potential translational relevance of this mechanism. Collectively, these findings suggest that rapid erasure of repressive histone marks by KDM7A and UTX is essential for NF-κB-dependent regulation of genes that control inflammatory responses of ECs.

Clinical outcomes and predictors of delayed echocardiographic response to cardiac resynchronization therapy.

INTRODUCTION: The clinical outcomes and mechanisms of delayed responses to cardiac resynchronization therapy (CRT) remain unclear. We aimed to investigate the differences in outcomes and gain insight into the mechanisms of early and delayed responses to CRT. METHODS: This retrospective study included 110 patients who underwent CRT implantation. Positive response to CRT was defined as ≥15% reduction of left ventricular (LV) end-systolic volume on echocardiography at 1 year (early phase) and 3 years (delayed phase) after implantation. The latest mechanical activation site (LMAS) of the LV was identified using two-dimensional speckle-tracking radial strain analysis. RESULTS: Seventy-eight (71%) patients exhibited an early response 1 year after CRT implantation. Of 32 non-responders in the early phase, 12 (38%) demonstrated a delayed response, and 20 (62%) were classified as non-responders after 3 years. During the follow-up time of 10.3 ± 0.5 years, the delayed and early responders had a similar prognosis of mortality and heart failure (HF) hospitalization. In contrast, non-responders had a worse prognosis. Multivariate analysis revealed that a longer duration (months) between initial HF hospitalization and CRT (odds ratio [OR]: 1.126; 95% confidence interval [CI]: 1.036-1.222; p = .005), non-exact concordance of LV lead location with LMAS (OR: 32.744; 95% CI: 1.101-973.518; p = .044), and pre-QRS duration (OR: 0.901; 95% CI: 0.827-0.981; p = .016) were independent predictors of delayed response to CRT compared with early response. CONCLUSION: The prognoses were similar regardless of the response time after CRT. A longer history of HF, suboptimal LV lead position, and shorter pre-QRS duration were related to delayed response than early response.

Comparison of novel intrinsic versus conventional antitachycardia pacing for ventricular tachycardia among implantable cardioverter-defibrillator recipients.

INTRODUCTION: Intrinsic antitachycardia pacing (iATP) is a novel automated antitachycardia pacing (ATP) that provides individual treatment to terminate ventricular tachycardia (VT). However, the clinical efficacy of iATP in comparison with conventional ATP is unknown. We aim to compare the termination rate of VT between iATP and conventional ATP in patients with implantable cardioverter-defibrillators using a unique setting of different sequential orders of both ATP algorisms. METHODS: Patients with the iATP algorithm were assigned to iATP-first and conventional ATP-first groups sequentially. In the iATP-first group, a maximum of seven iATP sequences were delivered, followed by conventional burst and ramp pacing. In contrast, in the conventional ATP-first group, two bursts and ramp pacing were initially programmed, followed by iATP sequences. We compared the success rates of VT termination in the first and secondary programmed ATP zones between the two groups. RESULTS: Fifty-eight and 56 patients were enrolled in the iATP-first and conventional ATP-first groups, and 67 and 44 VTs were analyzed in each group, respectively. At the first single ATP therapy, success rates were 64% and 70% in the iATP and conventional groups, respectively. At the end of the first iATP treatment zone, the success rate increased from 64% to 85%. Moreover, secondary iATP therapy following the failure of conventional ATPs increased the success rate from 80% to 93%. There was a significant benefit of alternative iATP for VT termination compared to secondary conventional ATP (100% vs. 33%, p = .028). CONCLUSIONS: iATP may be beneficial as a secondary therapy after failure of conventional ATP to terminate VT.

Alcohol and toxicological factors influencing fatal falls from height in the Greater Tokyo Area: a retrospective study.

Falls from height pose a significant public health concern in urban regions, including the highly urbanized Greater Tokyo Area. The Japanese population is characterized by high rates of suicide and psychoactive drug usage, underscoring the importance of investigating these attributes in falls from height. This study aimed to retrospectively analyze the alcohol and toxicological aspects influencing falls from height in the Greater Tokyo Area between 2014 and 2022 and compare the findings with existing reports on other populations. In total, 75 cases of falls from height and 159 cases of natural deaths were included. Consistent with previous findings, Fisher's exact test revealed a predominance of males (66.67%, 50/75) and young adults (57.33%, 43/75) in falls from height. Multivariate logistic regression analysis identified antidepressant usage as the most significant risk factor within the target population, while younger individuals under alcohol influence constituted another high-risk group. Notably, contradictory to other populations, female individuals involved in fatal falls in the Greater Tokyo Area exhibited a higher frequency of alcohol consumption than males (48.00%, 12/25 vs. 26.00%, 13/50), and most of them were associated with suicide (83.33%, 10/12). These findings elucidate the population characteristics that pose a high risk for fatal falls from height in Japan and can serve as a reference for other Asian populations residing in similar megacities.

Inflammatory myofibroblastic tumor directly invading the right first rib treated with oral steroids: a case report.

BACKGROUND: We present a case of an inflammatory myofibroblastic tumor cured with a short period of steroid administration, a treatment previously unreported for such cases. CASE PRESENTATION: A 49-year-old man had a chief complaint of chest pain for more than 3 days. Computed tomography (CT) revealed a tumoral lesion suspected to have infiltrated into the right first rib and intercostal muscles, with changes in lung parenchymal density around the lesion. The maximal standardized uptake value on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography was high (16.73), consistent with tumor presence. CT-guided biopsy revealed an inflammatory myofibroblastic tumor with no distant metastases. Surgery was indicated based on the disease course. However, he had received an oral steroid before the preoperative contrast-enhanced CT scan due to a history of bronchial asthma, and subsequent CT showed that the tumor shrank in size after administration; he has been recurrence-free for more than a year. CONCLUSIONS: Surgery is still the first choice for inflammatory myofibroblastic tumors, as the disease can metastasize and relapse; however, this condition can also be cured with a short period of steroid therapy.

A novel practical algorithm using machine learning to differentiate outflow tract ventricular arrhythmia origins.

INTRODUCTION: Diagnosis of outflow tract ventricular arrhythmia (OTVA) localization by an electrocardiographic complex is key to successful catheter ablation for OTVA. However, diagnosing the origin of OTVA with a precordial transition in lead V3 (V3TZ) is challenging. This study aimed to create the best practical electrocardiogram algorithm to differentiate the left ventricular outflow tract (LVOT) from the right ventricular outflow tract (RVOT) of OTVA origin with V3TZ using machine learning. METHODS: Of 498 consecutive patients undergoing catheter ablation for OTVA, we included 104 patients who underwent ablation for OTVA with V3TZ and identified the origin of LVOT (n = 62) and RVOT (n = 42) from the results. We analyzed the standard 12-lead electrocardiogram preoperatively and measured 128 elements in each case. The study population was randomly divided into training group (70%) and testing group (30%), and decision tree analysis was performed using the measured elements as features. The performance of the algorithm created in the training group was verified in the testing group. RESULTS: Four measurements were identified as important features: the aVF/II R-wave ratio, the V2S/V3R index, the QRS amplitude in lead V3, and the R-wave deflection slope in lead V3. Among them, the aVF/II R-wave ratio and the V2S/V3R index had a particularly strong influence on the algorithm. The performance of this algorithm was extremely high, with an accuracy of 94.4%, precision of 91.5%, recall of 100%, and an F1-score of 0.96. CONCLUSIONS: The novel algorithm created using machine learning is useful in diagnosing the origin of OTVA with V3TZ.

Diagnostic and Cost Efficiency of the 0-h/1-h Rule-out and Rule-in Algorithm for Patients With Chest Pain in the Emergency Department.

BACKGROUND: This study investigated the economic impact of the European Society of Cardiology (ESC) clinical practice guideline recommendation of using the 0-h/1-h rule-out and rule-in algorithm with high-sensitivity cardiac troponin assays (0/1-h algorithm) to triage patients presenting with chest pain.Methods and Results: This post hoc cost-effectiveness evaluation (DROP-ACS; UMIN000030668) used deidentified electronic medical records from health insurance claims from 2 diagnostic centers in Japan. A cost-effectiveness analysis was conducted with 472 patients with care provided following the 0/1-h algorithm (Hospital A) and 427 patients following point-of-care testing (Hospital B). The clinical outcome of interest was all-cause mortality or subsequent myocardial infarction within 30 days of the index presentation. The sensitivity and specificity for the clinical outcome were 100% (95% confidence interval [CI] 91.1-100%) and 95.0% (95% CI 94.3-95.0%), respectively, in Hospital A and 92.9% (95% CI 69.6-98.7%) and 89.8% (95% CI 89.0-90.0%), respectively, in Hospital B. If the diagnostic accuracy of the 0/1-h algorithm was implemented in Hospital B, it is expected that the number of urgent (<24-h) coronary angiograms would decrease by 50%. Incorporating this assumption, implementing the 0/1-h algorithm could potentially reduce medical costs by JPY4,033,874 (95% CI JPY3,440,346-4,627,402) in Hospital B (JPY9,447 per patient; 95% CI JPY 8,057-10,837 per patient). CONCLUSIONS: The ESC 0/1-h algorithm was efficient for risk stratification and for reducing medical costs.

A rare case of delayed complete lead dislodgement after deep septal pacing: A hidden risk of the specific procedure.

Deep septal ventricular pacing is a recently developed physiological pacing modality with good efficacy; however, it has a potential risk of unusual complications. Here, we report a patient with pacing failure and spontaneous, complete lead dislodgement after >2 years of deep septal pacing, possibly caused by systemic bacterial infection and specific lead behavior in the septal myocardium. This case report may implicate a hidden risk of unusual complications in deep septal pacing.

Cloning and Characterization of Cyp7a1 and Cyp27a1 Genes from the Non-Parasitic Japanese Lamprey Lethenteron reissneri.

Two cytochrome P450 genes homologous to human CYP7A1 and CYP27A1 were cloned from the non-parasitic Japanese lamprey Lethenteron reissneri. Lamprey cyp7a1 mRNA had varied expression levels among individuals: about four orders of magnitude differences in larval liver and nearly three orders of magnitude differences in male adult liver. Overexpressed Cyp7a1 protein tagged with green fluorescent protein (GFP) was localized to the endoplasmic reticulum. Lamprey cyp27a1 mRNA had relatively constant expression levels: within two orders of magnitude differences in larvae and adult liver and intestine. GFP-tagged Cyp27a1 protein was localized to mitochondria. The expression profiles of lamprey cyp7a1 and cyp27a1 genes and the cellular localizations of their products were in good agreement with their counterparts in mammals, where these two P450s catalyze initial hydroxylation reactions of cholesterol in classical and alternative pathways of bile acid synthesis, respectively. The cyp7a1 mRNA levels in adult male liver showed significant negative correlations to both body weight and total length of the animal, implying the involvement of the gene in the production of female-attractive pheromones in sexually matured male livers. The lamprey Cyp7a1 contains a long extension of 116 amino acids between helices D and E of the protein. Possible roles of this extension in regulating the enzymatic activity of lamprey Cyp7a1 are discussed.

The 3 × 120° rotary mechanism of Paracoccus denitrificans F1-ATPase is different from that of the bacterial and mitochondrial F1-ATPases.

The rotation of Paracoccus denitrificans F1-ATPase (PdF1) was studied using single-molecule microscopy. At all concentrations of adenosine triphosphate (ATP) or a slowly hydrolyzable ATP analog (ATPγS), above or below Km, PdF1 showed three dwells per turn, each separated by 120°. Analysis of dwell time between steps showed that PdF1 executes binding, hydrolysis, and probably product release at the same dwell. The comparison of ATP binding and catalytic pauses in single PdF1 molecules suggested that PdF1 executes both elementary events at the same rotary position. This point was confirmed in an inhibition experiment with a nonhydrolyzable ATP analog (AMP-PNP). Rotation assays in the presence of adenosine diphosphate (ADP) or inorganic phosphate at physiological concentrations did not reveal any obvious substeps. Although the possibility of the existence of substeps remains, all of the datasets show that PdF1 is principally a three-stepping motor similar to bacterial vacuolar (V1)-ATPase from Thermus thermophilus This contrasts with all other known F1-ATPases that show six or nine dwells per turn, conducting ATP binding and hydrolysis at different dwells. Pauses by persistent Mg-ADP inhibition or the inhibitory ζ-subunit were also found at the same angular position of the rotation dwell, supporting the simplified chemomechanical scheme of PdF1 Comprehensive analysis of rotary catalysis of F1 from different species, including PdF1, suggests a clear trend in the correlation between the numbers of rotary steps of F1 and Fo domains of F-ATP synthase. F1 motors with more distinctive steps are coupled with proton-conducting Fo rings with fewer proteolipid subunits, giving insight into the design principle the F1Fo of ATP synthase.

A New Boron-Rhodamine-Containing Carboxylic Acid as a Sugar Chemosensor.

We propose a boron-rhodamine-containing carboxylic acid (BRhoC) substance as a new sugar chemosensor. BRhoC was obtained by the Friedel-Crafts reaction of 4-formylbenzoic acid and N,N-dimethylphenylboronic acid, followed by chloranil oxidation. In an aqueous buffer solution at pH 7.4, BRhoC exhibited an absorption maximum (Absmax) at 621 nm. Its molar absorption coefficient at Absmax was calculated to be 1.4 × 105 M-1 cm-1, and it exhibited an emission maximum (Emmax) at 644 nm for the excitation at 621 nm. The quantum yield of BRhoC in CH3OH was calculated to be 0.16. The borinate group of BRhoC reacted with a diol moiety of sugar to form a cyclic ester, which induced a change in the absorbance and fluorescence spectra. An increase in the D-fructose (Fru) concentration resulted in the red shift of the Absmax (621 nm without sugar and 637 nm with 100 mM Fru) and Emmax (644 nm without sugar and 658 nm with 100 mM Fru) peaks. From the curve fitting of the plots of the fluorescence intensity ratio at 644 nm and 658 nm, the binding constants (K) were determined to be 2.3 × 102 M-1 and 3.1 M-1 for Fru and D-glucose, respectively. The sugar-binding ability and presence of a carboxyl group render BRhoC a suitable building block for the fabrication of highly advanced chemosensors.

Pathophysiology and Treatment of Chronic Thromboembolic Pulmonary Hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a condition in which an organic thrombus remains in the pulmonary artery (PA) even after receiving anticoagulation therapy for more than 3 months and is complicated by pulmonary hypertension (PH), leading to right-sided heart failure and death. CTEPH is a progressive pulmonary vascular disease with a poor prognosis if left untreated. The standard treatment for CTEPH is pulmonary endarterectomy (PEA), which is usually performed only in specialized centers. In recent years, balloon pulmonary angioplasty (BPA) and drug therapy for CTEPH have also shown good results. This review discusses the complex pathogenesis of CTEPH and presents the standard of care, PEA, as well as a new device called BPA, which is showing remarkable progress in efficacy and safety. Additionally, several drugs are now demonstrating established evidence of efficacy in treating CTEPH.

Characteristics of successful reactive atrial-based antitachycardia pacing in patients with cardiac implantable electronic devices: History of catheter ablation of atrial fibrillation as a predictor of high treatment efficacy.

INTRODUCTION: Reactive atrial-based antitachycardia pacing (rATP) in patients with cardiac implantable electronic devices (CIEDs) suppresses the progression of atrial fibrillation (AF) to the persistent form. However, the clinical factors associated with successful reactive atrial-based antitachycardia pacing (rATP) treatment are unknown. This study aimed to examine the predictors of high rATP efficacy in patients with CIEDs. METHODS: The data of 101,325 rATP-treated atrial tachyarrhythmia (AT/AF) episodes in 51 patients, obtained through remote monitoring and device interrogation, were analyzed. The study population was divided into the high and low efficacy groups based on the overall median success rate of rATP. Clinical characteristics were compared between the two groups. RESULTS: During a follow-up period of 28.6 ± 8.6 months, the median success rate was 43.7% (31.5%-64.9%). The prevalence of a history of catheter ablation of AF was significantly higher in the high efficacy group than in the low efficacy group (73.0% vs. 44.0%, p = .048) and was the only independent predictor of high rATP efficacy (odds ratio, 3.45; p = .038). The rATP success rate in patients with (n = 30) and without (n = 21) a history of catheter ablation was 53.9% (40.0%-67.5%) and 36.4% (22.2%-47.7%), respectively (p = .012). The effect of rATP after ablation was more pronounced in patients with long cycle length episodes (≥75% of AT/AF sequences having a cycle length of 200-449 ms) (67.3% [46.0%-73.6%] vs. 30.6% [18.1%-60.3%], p = .027). The high efficacy group had a significantly lower incidence of AT/AF lasting ≥1, ≥7, and ≥30 days than the low efficacy group. CONCLUSION: rATP combined with catheter ablation therapy is effective in suppressing AT/AF.

Digital-optical computational imaging capable of end-point logic operations.

In this study, digital-optical computational imaging is proposed for object data transmission with a capability to achieve end-point logic operations over free-space data transmission. The framework is regarded as an extension of computational imaging using digital-optical codes originally developed for digital optical computing. Spatial code patterns for optical logic operations are extended to digital-optical codes in the temporal and spectral domains. The physical form of the digital-optical codes is selected, as appropriate, for the situation in use, and different forms can be combined to increase the data-transmission bandwidth. The encoded signals are transferred over free space and decoded by a simple procedure on the destination device, thus enabling logic operations at the end-point of the data transmission. To utilize the benefits of digital processing, a data-transfer mode is introduced which assigns preprocessing for the signals to be encoded and the end-point processing. As a demonstration of the proposed method, an experimental testbed was constructed assuming data transmission from sensor nodes to a gateway device appearing in the Internet of Things. In the experiment, encrypted signals of the sensor nodes, which were encoded by spatial digital-optical codes on RGB channels, were captured as an image, and the original signals were retrieved correctly by an end-point exclusive OR operation.

Depolarization and repolarization dynamics after His-bundle pacing: Comparison with right ventricular pacing and native ventricular conduction.

BACKGROUND: The current study aimed to evaluate changes in electrical depolarization and repolarization parameters after His-bundle pacing (HBP) compared with right ventricular pacing (RVP) and its association with ventricular arrhythmia (VA). METHODS: Forty-one patients (13 with HBP, 14 with RVP, and 14 controls [AAI mode]) were evaluated. After continuous pacing algorithm, QRS duration, QT interval, QTc, JT interval, T-peak to T-end (Tpe), and Tpe/QT ratio were measured on electrocardiography at baseline and 1 week, 1 month, and 6 months postoperatively. We investigated VA occurrence and adverse events after implantation. RESULTS: At 6 months, QRS duration was significantly shorter in the HBP (121.6 ± 15.6 ms) than in the RVP (150.1 ± 14.9 ms) group. The QT intervals were lower in the HBP (424.0 ± 40.9 ms) and control (405.9 ± 23.0 ms) groups than in the RVP (453.0 ± 40.2 ms) group. The Tpe and Tpe/QT ratios at 6 months differed significantly between the HBP and RVP groups (Tpe, 69.8 ± 19.7 ms vs 87.4 ± 11.9 ms and Tpe/QT, 0.16 ± 0.03 vs 0.19 ± 0.02, respectively). The Tpe and Tpe/QT ratios were similarly shortened in the HBP and control groups. VA occurred less frequently in the HBP (15%) and control (7.1%) groups than in the RVP (50%) group (p = 0.020). The non-RVP group showed significantly lower rates of VA and major adverse events than the RVP group. Patients with VA demonstrated significantly longer QRS duration, QT interval, Tpe, and Tpe/QT at 6 months than those without VA. CONCLUSION: HBP showed better depolarization and repolarization stability than RVP.

Evaluation of the Novel Automated Anti-Tachycardia Pacing Algorithm Successfully Terminating Sustained Monomorphic Ventricular Tachycardia in an Electrophysiology Study.

We report the usefulness of novel automated anti-tachycardia pacing (ATP) for ventricular tachycardia (VT) termination evaluated in an electrophysiology study. This intrinsic, automated ATP with an implanted cardiac resynchronization therapy-defibrillator successfully terminated the sustained VT, which had not been suppressed by repetitive burst pacing from the electrode catheter. The reproduction of programed pacing of the automated ATP by a right ventricular electrode catheter was effective in terminating VT, and this termination was absolute and reproducible. Further detailed assessment in an electrophysiology study could highlight the algorithm of the automated ATP and its possible benefit in terminating the reentrant VT.

Identification of OPN3 as associated with non-syndromic oligodontia in a Japanese population.

Tooth agenesis is one of the most frequent congenital abnormalities found in the maxillofacial region. Oligodontia, a severe form of tooth agenesis, occurs as an isolated anomaly or as a syndromic feature. We performed whole exome sequencing analyses to identify causative mutation in a Japanese family with three affected individuals with non-syndromic oligodontia. After variant filtering procedures and validation by Sanger sequencing, we identified one missense mutation (c.668 C > T, p.Gly223Asp) in OPN3 at 1q43, encoding a photosensitive G-protein-coupled receptor (GPCR) expressed in various tissues including brain, liver, and adipose. This mutation was predicted to be pathogenic in silico and was not found in the public databases. We further examined 48 genetically unrelated cases by targeted sequencing of the OPN3 gene region and found one additional missense variant in this gene (c.768 C > T, p.Met256Ile) that was also predicted to be pathogenic. Localization of OPN3 protein by immunohistochemical analysis using mouse embryo revealed its specific expression in the tooth gems from bud to bell stages and their surrounding tissues. These results indicated that OPN3 was involved in non-syndromic oligodontia, which has made an anchoring point for clinical application including DNA diagnostics.

Spatial-light-modulator-based optical-fiber joint switch for few-mode multicore fibers.

To realize simplified cost-efficient optical networks with routing flexibility and scaling potential, a spatial-light-modulator-based optical-fiber joint switch for few-mode multicore fibers is proposed herein, which can route all spatial channels together as a unit. Numerical simulations and experiments were performed, and the results show that the signal paths for a 6-mode 19-core fiber can be simultaneously switched to the target output ports using the proposed method, and the mode-field patterns of the diffracted light can be maintained after joint switching. Further, the maximum port crosstalk can be reduced considerably from -11.6 to -25.1 dB by changing the position of the output port in the proposed method.

Single-Round DNA Aptamer Selection by Combined Use of Capillary Electrophoresis and Next Generation Sequencing: An Aptaomics Approach for Identifying Unique Functional Protein-Binding DNA Aptamers.

In DNA aptamer selection, existing methods do not discriminate aptamer sequences based on their binding affinity and function and the reproducibility of the selection is often poor, even for the selection of well-known aptamers like those that bind the commonly used model protein thrombin. In the present study, a novel single-round selection method (SR-CE selection) was developed by combining capillary electrophoresis (CE) with next generation sequencing. Using SR-CE selection, a successful semi-quantitative and semi-comprehensive aptamer selection for thrombin was demonstrated with high reproducibility for the first time. Selection rules based on dissociation equilibria and kinetics were devised to obtain families of analogous sequences. Selected sequences of the same family were shown to bind thrombin with high affinity. Furthermore, data acquired from SR-CE selection was mined by creating sub-libraries that were categorized by the functionality of the aptamers (e. g., pre-organized aptamers versus structure-induced aptamers). Using this approach, a novel fluorescent molecular recognition sensor for thrombin with nanomolar detection limits was discovered. Thus, in this proof-of-concept report, we have demonstrated the potential of a "DNA Aptaomics" approach to systematically design functional aptamers as well as to obtain high affinity aptamers.

Brønsted acid-induced transannulation of the phytochemical zerumbone.

The sesquiterpene zerumbone was treated with HCl in ethyl acetate under the light-protected condition, and the time-dependent conversions were analyzed by gas chromatography. Nine products were isolated, and their structures were revealed by several NMR measurements such as 1H NMR, 13C{1H} NMR, distortionless enhancement by polarization transfer (DEPT)-135, 1H-1H correlation spectroscopy (COSY), 1H-13C heteronuclear multiple quantum coherence (HMQC), and 1H-13C heteronuclear multiple bond coherence (HMBC). The X-ray crystallography determined the stereochemistries of the three products and the two derivatives. After all, this acidic reaction was found to provide the (2Z,6E,10E)-isomer, the two HCl adducts, the two 7,6-bicyclic compounds, the valence isomers cycloheptatriene and norcaradiene, and the two dihydronaphthalenes. Based on the product analyses of the reactions from the isolated intermediates as well as the mechanistic considerations, these products were arranged into two paths: one of the paths ended in the two dihydronaphthalenes the same as previously reported under the Lewis acid condition; the other ended in the 7,6-bicyclic compound, the epimer of which was known. In addition, density functional theory (DFT) calculations indicated that the (2Z,6E,10E)-isomer was more stable than the (2E,6E,10Z)-isomer as well as that the activation energy for the isomerization at the C2-C3 double bond decreased to half by protonation. The closely examined reaction mechanisms under the simple acidic condition were established upon the intensive characterization of the intermediates and products, and these findings would add to the attractive value of zerumbone and would help understand the unknown biosynthetic pathway around sesquiterpenoids.