Nanoscale dosimetry for a radioisotope-labeled metal nanoparticle using MCNP6.2 and Geant4.

BACKGROUND: Metal nanoparticles (MNPs) labeled with radioisotopes (RIs) are utilized as radio-enhancers due to their ability to amplify the radiation dose in their immediate vicinity. A thorough understanding of nanoscale dosimetry around MNPs enables their effective application in radiotherapy. However, nanoscale dosimetry around MNPs still requires further investigation. PURPOSE: This study aims to provide insight into the radio-enhancement effects of MNPs by elucidating nanoscale dosimetry surrounding MNPs labeled with Auger-emitting RIs. We particularly focus on distinguishing the respective dose contributions of photons and electrons emitted by Auger-emitting RIs in the context of dose enhancement. METHODS: A 50 nm diameter NP of silver (Ag) core and gold (Au) shell (Ag@Au NP) was assumed to emit mono-energetic electrons and photons (3, 5, 10, 20, and 30 keV), or the energy spectrum corresponding to one of three Auger-emitting RIs (103Pd, 125I, and 131Cs) from the Ag core. Nanoscale radial dose distributions around a single radioactive Ag@Au NP were evaluated in spherical shells of water. Monte Carlo simulations were conducted using single-event and track structure transport methods implemented in MCNP6.2 and Geant4-DNA-Au physics, respectively. To evaluate the extent of radio-enhancement by the Ag@Au NP, two scenarios were considered: Ag@Au NPs (Au shell included) and Ag@water NPs (Au shell replaced by water). RESULTS: The radial doses of 10, 20, and 30 keV electrons estimated by both codes were comparable. However, the radial doses of 3 and 5 keV electrons by MCNP6.2 were much larger near the NP surface than those by Geant4. There was a dose enhancement of a few % to tens % by the Au shell in the region of the NP surface to 10 µm, depending on the electron energy. The radial doses of photons with the Au shell were higher up to their secondary electron ranges than those without the Au shell. The maximum dose enhancement factor of photons occurred at 20 keV and was 63.4 by MCNP6.2 and 50.5 by Geant4. The overall radial doses of electrons were 1-2 orders of magnitude larger than those of photons. As a result, in cases of RIs emitting both electrons and photons, the radial doses up to electron ranges were dominantly governed by electrons. The dose enhancement estimated by both codes for the RIs ranged from a few % except in the immediate vicinity of the NP surface. CONCLUSION: Given the dominant contribution of electrons to radial doses of MNP labeled with Auger-emitting RIs, physical dose enhancement expected by interactions with photons was hindered. Since there are no available RIs emitting exclusively photons, achieving enhanced physical doses within a cell through a combination of MNPs and RIs appears currently unattainable. The radial doses of photons near the NP surface exhibited considerable discrepancies between the codes, primarily attributed to low-energy electrons. The difference may arise from higher cross-sections of Au inelastic scattering in Geant4-DNA-Au compared to MCNP6.2.

Efficacy and safety of inflator-monitored balloon-occluded retrograde transvenous obliteration for gastric varices.

PURPOSE: To investigate the diagnostic efficacy of inflator-monitored balloon-occluded retrograde transvenous obliteration (ImBRTO) in detecting balloon rupture and to evaluate the efficacy and safety of the ImBRTO in treating gastric varices. METHODS: Between June 2018 and June 2024, 31 consecutive patients (age: 61.7 ± 12.4 years; male 20, female 11) underwent ImBRTO for gastric varices. An occlusion balloon was inflated with an inflation device to monitor for balloon rupture during sclerosing, maintaining the balloon inflation for at least 3 h. RESULTS: The technical success rate was 100%. The incidence of balloon rupture was 6.5% (2/31), both diagnosed by a pressure drop in the inflation device. In one of the two patients, catheter replacement and an additional injection of a sclerosing agent were required due to early balloon rupture (< 3 h). Clinical success and complete elimination of gastric varices were achieved in all cases. No procedure-related complications were observed. There were no cases of recurrent variceal bleeding at the end of the follow-up (median: 5.2 months). CONCLUSION: ImBRTO proves to be an effective and safe technique for treating gastric varices. The real-time monitoring of balloon integrity allows for timely decisions, resulting in excellent clinical outcomes.

Medication burden reduction and early clinical benefit through aripiprazole once monthly in schizophrenia patients with polypharmacy.

Antipsychotic polypharmacy is commonly used in clinical settings, with a growing trend in using long-acting injections to mitigate many side effects of polypharmacy. A previous study demonstrated that long-acting aripiprazole once-monthly (AOM) injection increased treatment adherence, restored functionality, and improved symptoms. However, there is insufficient evidence to demonstrate the therapeutic effects of AOM in polypharmacy practice. This observational study aimed to investigate the real-world clinical benefits and effectiveness of AOM by assessing changes in drug dosage, the number of drugs, clinical functioning, psychotic symptoms, and the duration of drug efficacy. Study participants were recruited from eight study sites, with the baseline visit marking the initiation of drug treatment. Clinical and demographic data were collected from medical records at screening, baseline, and months 1, 3, 6, 9, and 12. Over 12 months, we analyzed changes in drug dosage, the number of drugs, and scores of the Positive and Negative Syndrome Scale-6 (PANSS-6), Global Assessment of Functioning (GAF), and Clinical Global Impression-Severity (CGIS). Data from 139 participants were analyzed. Total 12-month antipsychotic doses calculated in chlorpromazine equivalents (CPE) were reduced by 32.6%. A comparison of total monthly antipsychotic doses in CPE between the first and last months showed a 24.6% reduction in the dose. Additionally, the quantity of benzodiazepine tablets/capsules, total benzodiazepine doses calculated in lorazepam equivalents, and quantity of tablets/capsules of mood stabilizers, anticholinergics, and beta blockers were significantly reduced. GAF scores increased by 14.1% over 12 months, and PANSS-6 total scores reduced by 17.3% over 12 months, with significant differences observed from month 1 and baseline, respectively. The scores steadily improved until month 9 compared to those of the previous months, continuing to improve through month 12. The CGI-S score reduced by 14.3% over 12 months, showing a significant decrease from month 1 and a steady improvement until month 6, maintaining this improvement until month 12. In conclusion, this study demonstrated the early effectiveness of AOM in treating Korean patients with schizophrenia on polypharmacy. AOM improved function and clinical symptoms in patients with schizophrenia from treatment onset and caused a decrease in the quantity and dosage of drugs taken by the patients.

Enhancing procedural decision making with cone beam CT in renal artery embolization.

Cone-beam computed tomography (CBCT) has proven to be a safe and effective adjunctive imaging tool for interventional radiology. Nevertheless, limited studies have examined the application of CBCT in renal artery embolization (RAE). The objective of this study is to evaluate the role of CBCT in intra-procedural decision-making for RAE. This multicenter retrospective study included 40 consecutive patients (age: 55.9 ± 16.5 years; male, 55%) who underwent CBCT during RAE from January 2019 to January 2023. The additional information provided by CBCT was classified into Category 1 (no additional information), Category 2 (more information without changing the treatment plan), and Category 3 (valuable information that led to a change in the treatment plan). CBCT did not add unique information for four patients (10%) classified as Category 1. CBCT clarified ambiguous angiographic findings and confirmed the existing treatment plan for 19 patients (47.5%) graded as Category 2; complex vascular anatomy was explained (n = 13), and a correlation between vascular territory and target lesion was established (n = 6). CBCT offered valuable information that was not visible on digital subtraction angiography and changed the treatment plan for 17 patients categorized as Category 3; a mismatch between the vascular territory and the target lesion led to the identification of alternative (n = 3) and additional feeders (n = 8); and the extent of embolization was reduced by using automatic feeder detection software (n = 6). CBCT is an efficient tool that aids in the decision-making process during the embolization procedure by providing supplementary imaging information. This additional information enables the confident identification of target vessels, facilitates superselective embolization, prevents non-target embolization, and helps locate missing feeders.

Ferroelectric Modulation of Quantum Emitters in Monolayer WS2.

Quantum photonics promises significant advances in secure communications, metrology, sensing, and information processing/computation. Single-photon sources are fundamental to this endeavor. However, the lack of high-quality single photon sources remains a significant obstacle. We present here a paradigm for the control of single photon emitters (SPEs) and single photon purity by integrating monolayer WS2 with the organic ferroelectric polymer poly(vinylidene fluoride-co-trifluoroethylene) (P(VDF-TrFE)). We demonstrate that the ferroelectric domains in the P(VDF-TrFE) film control the purity of single photon emission from the adjacent WS2. By switching the ferroelectric polarization, we reversibly tune the single photon purity between the semiclassical and quantum light regimes, with single photon purities as high as 94%. This demonstrates a method for modulating and encoding quantum photonic information, complementing more complex approaches. This multidimensional heterostructure introduces an approach for control of quantum emitters by combining the nonvolatile ferroic properties of a ferroelectric with the radiative properties of the zero-dimensional atomic-scale emitters embedded in the two-dimensional WS2 semiconductor monolayer.

TF-EPI: an interpretable enhancer-promoter interaction detection method based on Transformer.

The detection of enhancer-promoter interactions (EPIs) is crucial for understanding gene expression regulation, disease mechanisms, and more. In this study, we developed TF-EPI, a deep learning model based on Transformer designed to detect these interactions solely from DNA sequences. The performance of TF-EPI surpassed that of other state-of-the-art methods on multiple benchmark datasets. Importantly, by utilizing the attention mechanism of the Transformer, we identified distinct cell type-specific motifs and sequences in enhancers and promoters, which were validated against databases such as JASPAR and UniBind, highlighting the potential of our method in discovering new biological insights. Moreover, our analysis of the transcription factors (TFs) corresponding to these motifs and short sequence pairs revealed the heterogeneity and commonality of gene regulatory mechanisms and demonstrated the ability to identify TFs relevant to the source information of the cell line. Finally, the introduction of transfer learning can mitigate the challenges posed by cell type-specific gene regulation, yielding enhanced accuracy in cross-cell line EPI detection. Overall, our work unveils important sequence information for the investigation of enhancer-promoter pairs based on the attention mechanism of the Transformer, providing an important milestone in the investigation of cis-regulatory grammar.

Psychological Distress Trends and Effect of Media Exposure Among Community Residents After the Seoul Halloween Crowd Crush.

BACKGROUND: It is unclear how exposure to and perception of community trauma creates a mental health burden. This study aimed to examine the psychological distress trends among community residents in acute stress reaction, acute stress disorder, and post-traumatic stress disorder phases following the Seoul Halloween crowd crush. METHODS: A three-wave repeated cross-sectional survey was conducted with participants after the incident. Analysis of covariance (ANCOVA) with post hoc Bonferroni test was adopted to examine temporal changes in psychological distress and psychological outcomes resulting from media impacts. A two-way ANCOVA was adopted to examine the interaction effects of time and relevance to victims on psychological distress. RESULTS: A total of 807, 1,703, and 2,220 individuals participated in the three waves. Anxiety (estimated mean [standard error of the mean]: 2.28 [0.03] vs. 2.12 [0.02] vs. 2.03 [0.02]; P < 0.001), depression (2.22 [0.03] vs. 2.01 [0.02] vs. 1.90 [0.02]; P < 0.001), and anger (2.70 [0.03] vs. 2.66 [0.02] vs. 2.49 [0.02]; P < 0.001) gradually improved. However, sense of safety initially worsened and did not recover well (2.96 [0.03] vs. 2.75 [0.02] vs. 2.77 [0.02]; P < 0.001). The interaction effect of time and relevance to the victim were significant in depression (P for interaction = 0.049), anger (P for interaction = 0.016), and sense of safety (P for interaction = 0.004). Among participants unrelated to the victim, those exposed to graphics exhibited higher levels of anxiety (2.09 [0.02] vs. 1.87 [0.07]; P = 0.002), depression (1.99 [0.02] vs. 1.83 [0.07]; P = 0.020), and anger (2.71 [0.03] vs. 2.47 [0.08]; P = 0.003) at W2 and higher anger (2.49 [0.02] vs. 2.31 [0.06]; P = 0.005) at W3. CONCLUSION: Community residents indirectly exposed to trauma also experienced psychological distress in the early stages after the incident. A significant impact of media which might have served as a conduit for unfiltered graphics and rumors was also indicated.

Adiponectin Prevents Skin Inflammation in Rosacea by Suppressing S6 Phosphorylation in Keratinocytes.

Numerous recent evidence highlights epidemiological connections between rosacea and metabolic disorders. However, the precise path through which metabolic factors impact rosacea risk is still unclear. Therefore, this study aims to investigate the role of adiponectin, a crucial adipokine that regulates metabolic homeostasis, in the pathogenesis of rosacea. We elucidated a detrimental feedback loop between rosacea-like skin inflammation and decreased levels of skin adiponectin. To elaborate, rosacea lesional skin exhibits diminished adiponectin expression compared with nonlesional areas in the same patients. Induction of rosacea-like inflammation reduced adiponectin levels in the skin by generating inflammatory cytokines that suppress adiponectin production from subcutaneous adipocytes. Conversely, complete depletion of adiponectin exacerbated rosacea-like features in the mouse model. Mechanistically, adiponectin deficiency led to heightened S6 phosphorylation, a marker of the mTORC1 signaling pathway, in the epidermis. Adiponectin significantly inhibited S6 phosphorylation in cultured keratinocytes. Notably, replenishing adiponectin whole protein or topically applying an agonist for adiponectin receptor 1 successfully improved rosacea-like features in mice. This study contributes to understanding the role of adiponectin in skin inflammation associated with rosacea pathophysiology, suggesting that restoring adiponectin function in the skin could be a potential therapeutic strategy.

Case Report: Vertical muscle-sparing latissimus dorsi flap in the reconstruction of chronic radiation-induced chest wall ulcers after breast cancer surgery: a case series.

Introduction: Radiation therapy, a standard postoperative treatment for breast cancer, can lead to chronic ulcers owing to compromised tissue healing. Accordingly, flap surgery using healthy tissues is essential for aesthetic and functional recovery. Although various flap techniques exist, each has its own drawbacks. This study introduces the vertical muscle-sparing latissimus dorsi flap as a superior alternative due to its comparative operative efficiency and tissue preservation. Case report: Two female patients aged 60 and 59 years with histories of breast cancer in their left breast treated with radiotherapy presented with chronic ulcers. The first patient had a 4 × 5 cm defect infiltrating the pleural space, while the second had a 15 × 9 cm defect after thoracic surgery for a bronchopleural fistula. In both cases, debridement was followed by reconstruction using a vertical muscle-sparing latissimus dorsi flap, thereby avoiding the need to change the patient's position and repeated draping during surgery. Both patients showed good postoperative recovery without significant complications. Results: The vertical muscle-sparing latissimus dorsi flap resulted in better adhesions and functional outcomes due to shorter surgical duration. Conclusion: The vertical muscle-sparing latissimus dorsi flap is an effective and efficient method for reconstructing radiation-induced chest wall ulcers in patients with breast cancer. Its application in the presented cases highlights its potential as a preferred option in similar clinical scenarios.

Clipless internal mammary artery harvesting for minimally invasive coronary artery bypass grafting using the shear-tip harmonic scalpel.

Background: The internal mammary artery (IMA) is the most commonly used graft in coronary artery bypass grafting (CABG) because of its superior long-term patency rate. However, its small diameter poses challenges in handling, and any vascular damage that may occur during harvesting can significantly affect surgical outcomes. The primary focus during IMA harvesting is to ensure safe and effective hemostasis without direct vascular injury, while ensuring secure and reliable ligation of the vascular branches. Various methods using multiple surgical instruments have been used for this purpose. Unlike traditional instruments, the shear-tip Harmonic scalpel offers more precise vessel branching control, while minimizing damage to surrounding tissues. In this study, we assessed the utility of the shear-tip Harmonic scalpel in patients undergoing minimally invasive coronary artery bypass grafting (MICABG). Methods: From April 2019 to May 2023, a total of 40 patients underwent MICABG. The IMA was harvested using the shear-tip Harmonic scalpel with a clipless skeletonized technique. In this cohort, 5 patients underwent complete endoscopic harvesting, while 34 patients underwent direct visualization harvesting through minimal thoracotomy. Graft patency was assessed by measuring a Doppler flowmeter in the bypass conduit. Results: Successful graft patency was achieved in all patients. The mean duration of IMA harvesting was 87 min. In total, 38 of the 40 patients underwent MICABG without the need for cardiopulmonary bypass, ensuring a stable procedure. There were no graft-related events or complications observed in any of the patients, and all were discharged without any issues. During a median follow-up period of 15.2 months, only one patient experienced graft occlusion necessitating intervention. Conclusions: The utilization of shear-tip Harmonic scalpel for IMA harvesting in MICABG is feasible and yields stable early results.

Compensatory strategies of dysphagia after anterior cervical spinal surgery: A case report.

RATIONALE: Dysphagia after anterior cervical discectomy and fusion (ACDF) is a common postoperative complication. However, information regarding rehabilitation strategies for postoperative dysphagia is limited. Herein, we report a compensatory strategy for treating dysphagia after ACDF. PATIENT CONCERNS: A 65-year-old Asian male presented with left arm pain and weakness for more than 1 month. Magnetic resonance imaging of the cervical spine revealed degenerative disc lesions and spinal stenosis at the C3 to C7 levels. The patient underwent ACDF at the C3 to C5 levels and artificial disc replacement at the C5 to C7 levels by right side approach. After surgery, the patient complained of difficulty swallowing. A video fluoroscopic swallowing study (VFSS) detected swallowing dysfunction in the pharyngeal phase, revealing an asymmetric pharyngeal residue in the anterior-posterior view. DIAGNOSIS: The patient was diagnosed with dysphagia after ACDF. INTERVENTIONS: Based on the VFSS findings, the patient underwent swallowing rehabilitation therapy and compensatory techniques, such as head rotation to the weak right side and head tilting to the robust left side. OUTCOMES: After 2 months of rehabilitation with compensatory techniques, food moved smoothly towards the robust side, and the subjective symptoms of dysphagia improved. LESSONS: Consequently, swallowing function post-ACDF surgery must be assessed; if unilateral dysphagia is detected, compensatory techniques may prove beneficial. This case study showed that, based on the objective findings of the VFSS, an effective swallowing compensation strategy can be established and applied to patients with postoperative dysphagia.

Outcomes of Aural Rehabilitation Provided in Person or by Telehealth Among Deaf/Hard of Hearing Young Children with Cochlear Implants or Hearing Aids.

Background: Cochlear implants and hearing aids may facilitate the development of listening and spoken language (LSL) in deaf/hard of hearing young children, but they require aural rehabilitation therapy-often unavailable outside urban areas-for optimal outcomes. This trial assessed the relative effectiveness of LSL therapy delivered either in person or by interactive video. The hypothesis was that telehealth service delivery would be noninferior to in-person therapy. Methods: Most parents refused randomization of their children to telehealth or in-person conditions; therefore, randomization was impossible. In consultation with the funder (NIDCD), the study design was modified. Parents were allowed to select their preferred study condition, and the study team was blinded to group membership. Forty-two families were in the in-person group and 35 in telehealth (40 and 30, respectively, after attrition). Primary endpoints were total score, auditory comprehension, and expressive communication on the Preschool Language Scale, 5th edition. There were several secondary speech, hearing, and language outcome measures. Assessments occurred at baseline and at follow-up after 6 months of LSL therapy. Results: Propensity scores were used to create two matched groups. At baseline, groups did not differ on PLS-5 scores. Change from baseline to F/U on age-equivalents for all three scores was nearly identical for both groups, although the telehealth group was younger, on average, than the in-person group. Discussion: Telehealth was noninferior to in-person services for all primary endpoints. For secondary outcomes, neither group demonstrated a significant advantage. Magnitudes of estimated group differences were small, suggesting nonsignificant differences not predominantly because of sample size. The telehealth group showed greater improvement on 15/24 of secondary language outcome measures. The findings provide evidence that telehealth is equivalent to in-person care for providing LSL therapy to young children with cochlear implants and hearing aids.

Integrative analysis of cancer multimodality data identifying COPS5 as a novel biomarker of diffuse large B-cell lymphoma.

Preventing, diagnosing, and treating diseases requires accurate clinical biomarkers, which remains challenging. Recently, advanced computational approaches have accelerated the discovery of promising biomarkers from high-dimensional multimodal data. Although machine-learning methods have greatly contributed to the research fields, handling data sparseness, which is not unusual in research settings, is still an issue as it leads to limited interpretability and performance in the presence of missing information. Here, we propose a novel pipeline integrating joint non-negative matrix factorization (JNMF), identifying key features within sparse high-dimensional heterogeneous data, and a biological pathway analysis, interpreting the functionality of features by detecting activated signaling pathways. By applying our pipeline to large-scale public cancer datasets, we identified sets of genomic features relevant to specific cancer types as common pattern modules (CPMs) of JNMF. We further detected COPS5 as a potential upstream regulator of pathways associated with diffuse large B-cell lymphoma (DLBCL). COPS5 exhibited co-overexpression with MYC, TP53, and BCL2, known DLBCL marker genes, and its high expression was correlated with a lower survival probability of DLBCL patients. Using the CRISPR-Cas9 system, we confirmed the tumor growth effect of COPS5, which suggests it as a novel prognostic biomarker for DLBCL. Our results highlight that integrating multiple high-dimensional data and effectively decomposing them to interpretable dimensions unravels hidden biological importance, which enhances the discovery of clinical biomarkers.

A GPU-accelerated Monte Carlo code, RT2for coupled transport of photon, electron/positron, and neutron.

Objective.This work aims to develop a graphics processing unit (GPU)-accelerated Monte Carlo code for the coupled transport of photon, electron/positron and neutron over a broad range of energies for medical applications.Approach.By separating the MC evolution of radiation into source, transport, and interaction kernels, the branch divergence was alleviated. The memory coalescence was achieved by vectorizing the access pattern in which the secondary particles were archived. To accelerate further particle tracking, ray-tracing hardware acceleration in the Nvidia OptiXTMframework was applied. For photon and electron/positron, the EGSnrc interaction modules were ported as a GPU-optimized configuration. For neutron, a group-wised transport based on NJOY21 preprocessed data was implemented. The developed code was validated against CPU-based FLUKA. Neutron, x-ray and electron beams incident on water and ICRP phantoms were simulated. The neutron energy group and the transport parameters of photon and electron were set to be the same in both codes. A single Nvidia RTX 4090 card was used in this code while all 20 threads of a single Intel Core i9-10900K node were used in FLUKA.Main results.The number of histories was set to ensure that statistical uncertainties lower than 2% for all voxels whose doses were larger than 20% of the maximum. In all cases, the dose differences in the voxels between the codes were within 2.5%. For photons and electrons, the developed code was 150-300 times faster than FLUKA in both geometries. For neutrons, the code was respectively 80 and 135 times faster in the water and ICRP phantoms than FLUKA.Significance.This study offers an appropriate solution for uncoalesced memory access and branch divergence commonly encountered in coupled MC transport on the GPU architecture. The formidable acceleration in computing times and accuracy shown in this study can promise a routine clinical use of MC simulations.

Sex Differences in the Association between Prolonged Sitting Time and Anxiety Prevalence among Korean Adults.

Sex differences in the effect of prolonged sitting time on anxiety symptoms have not yet been explored. This study examined the sex-specific association between prolonged sitting time and anxiety prevalence in Korean adults. Community-dwelling adults aged >18 years who underwent a cross-sectional structured study survey of physical activity and mental health tests were enrolled as part of the Kangbuk Samsung Hospital Cohort Study from 2012 to 2019. The prevalence of anxiety was evaluated using the Clinically Useful Anxiety Outcome Scale (CUXOS) questionnaire. The mean daily sitting time was 7.9 ± 3.4 h in men and 6.8 ± 3.6 h in women. After adjustments for possible confounding factors, the adjusted mean CUXOS score was the highest in participants sitting for ≥10 h, followed by 5-9 h, and <5 h, in that order. In the post-hoc Bonferroni analysis, there were significant differences in the adjusted mean CUXOS scores in group comparisons. A multivariate logistic regression analysis was conducted after adjusting for potential confounding factors. A prolonged sitting time was positively associated with an increased prevalence of anxiety in both men and women, with stronger associations in women than in men. It is necessary to prevent anxiety by adjusting or reducing sitting time in adults, especially women.

A Food Odorant, α-Ionone, Inhibits Skin Cancer Tumorigenesis by Activation of OR10A6.

SCOPE: This study aims to investigate the anticancer properties of α-ionone in squamous cell carcinoma (SCC). METHODS AND RESULTS: The expression of OR10A6 together with olfactory receptor signaling components is demonstrated in A431 human SCC cells via RT-PCR and qRT-PCR analysis. OR10A6 activation in A431 cells using the ligand α-ionone inhibits proliferation and migration but induces apoptosis which is confirmed by proliferation assay, colony formation, and western blotting. The mechanism involves the core proteins of the Hippo pathway, where the phosphorylation of large tumor suppressor kinase (LATS), yes-associated protein (YAP), and transcriptional coactivator with PDZ-binding motif (TAZ) is confirmed by western blotting. However, the anticancer effects of α-ionone are abrogated in A431 cells with OR10A6 gene knockdown. In A431 xenograft mouse model, the injection of α-ionone suppresses tumor growth, induces apoptosis, and increases phosphorylation of the LATS-YAP-TAZ signaling axis in the Hippo pathway. None of these effects are observed in xenografted tumors with OR10A6 gene knockdown. CONCLUSION: These findings collectively demonstrate that activation of ectopic OR OR10A6 by α-ionone in SCC cells stimulates the Hippo pathway and suppresses tumorigenesis both in vitro and in vivo, suggesting a novel therapeutic candidate for the treatment of SCC.

Fluoride scavengeable Sb2O3-functionalized poly(imide) separators for prolonged cycling of lithium-ion batteries.

Nanosize-controlled antimony oxides (Sb2O3) that can effectively scavenge fluoride species in a cell are incorporated into a PI separator to regulate its porous structure. The incorporation of the Sb2O3 layer onto the PI separator surface prevents the internal short circuit and efficiently removes fluoride species via chemical scavenging reactions, thereby resulting in stable cycling behaviors upon cycling.

ER-to-lysosome Ca2+ refilling followed by K+ efflux-coupled store-operated Ca2+ entry in inflammasome activation and metabolic inflammation.

We studied lysosomal Ca2+ in inflammasome. Lipopolysaccharide (LPS) + palmitic acid (PA) decreased lysosomal Ca2+ ([Ca2+]Lys) and increased [Ca2+]i through mitochondrial ROS, which was suppressed in Trpm2-KO macrophages. Inflammasome activation and metabolic inflammation in adipose tissue of high-fat diet (HFD)-fed mice were ameliorated by Trpm2 KO. ER→lysosome Ca2+ refilling occurred after lysosomal Ca2+ release whose blockade attenuated LPS + PA-induced inflammasome. Subsequently, store-operated Ca2+entry (SOCE) was activated whose inhibition suppressed inflammasome. SOCE was coupled with K+ efflux whose inhibition reduced ER Ca2+ content ([Ca2+]ER) and impaired [Ca2+]Lys recovery. LPS + PA activated KCa3.1 channel, a Ca2+-activated K+ channel. Inhibitors of KCa3.1 channel or Kcnn4 KO reduced [Ca2+]ER, attenuated increase of [Ca2+]i or inflammasome activation by LPS + PA, and ameliorated HFD-induced inflammasome or metabolic inflammation. Lysosomal Ca2+ release induced delayed JNK and ASC phosphorylation through CAMKII-ASK1. These results suggest a novel role of lysosomal Ca2+ release sustained by ER→lysosome Ca2+ refilling and K+ efflux through KCa3.1 channel in inflammasome activation and metabolic inflammation.

Requirement of ß subunit for the reduced voltage-gated Na+ current of a Brugada syndrome patient having novel double missense mutation (p.A385T/R504T) of SCN5A.

Mutations within the SCN5A gene, which encodes the α-subunit 5 (NaV1.5) of the voltage-gated Na+ channel, have been linked to three distinct cardiac arrhythmia disorders: long QT syndrome type 3, Brugada syndrome (BrS), and cardiac conduction disorder. In this study, we have identified novel missense mutations (p.A385T/R504T) within SCN5A in a patient exhibiting overlap arrhythmia phenotypes. This study aims to elucidate the functional consequences of SCN5A mutants (p.A385T/R504T) to understand the clinical phenotypes. Whole-cell patch-clamp technique was used to analyze the NaV1.5 current (INa) in HEK293 cells transfected with the wild-type and mutant SCN5A with or without SCN1B co-expression. The amplitude of INa was not altered in mutant SCN5A (p.A385T/R504T) alone. Furthermore, a rightward shift of the voltage-dependent inactivation and faster recovery from inactivation was observed, suggesting a gain-of-function state. Intriguingly, the coexpression of SCN1B with p.A385T/R504T revealed significant reduction of INa and slower recovery from inactivation, consistent with the loss-of-function in Na+ channels. The SCN1B dependent reduction of INa was also observed in a single mutation p.R504T, but p.A385T co-expressed with SCN1B showed no reduction. In contrast, the slower recovery from inactivation with SCN1B was observed in A385T while not in R504T. The expression of SCN1B is indispensable for the electrophysiological phenotype of BrS with the novel double mutations; p.A385T and p.R504T contributed to the slower recovery from inactivation and reduced current density of NaV1.5, respectively.