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Background The increasing prevalence of heated tobacco products (HTPs) has heightened concerns regarding their potential health risks. Previous studies have demonstrated the toxicity of cigarette smoke extract (CSE) from traditional tobacco's mainstream smoke, even after the removal of nicotine and tar. Our study aimed to investigate the cytotoxicity of CSE derived from HTPs and traditional tobacco, with a particular focus on the role of reactive oxygen species (ROS) and intracellular Ca.sup.2+. Methods A human oral squamous cell carcinoma (OSCC) cell line, HSC-3 was utilized. To prepare CSE, aerosols from HTPs (IQOS) and traditional tobacco products (1R6F reference cigarette) were collected into cell culture media. A cell viability assay, apoptosis assay, western blotting, and Fluo-4 assay were conducted. Changes in ROS levels were measured using electron spin resonance spectroscopy and the high-sensitivity 2ʹ,7ʹ-dichlorofluorescein diacetate assay. We performed a knockdown of calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) by shRNA lentivirus in OSCC cells. Results CSE from both HTPs and traditional tobacco exhibited cytotoxic effects in OSCC cells. Exposure to CSE from both sources led to an increase in intracellular Ca.sup.2+ concentration and induced p38 phosphorylation. Additionally, these extracts prompted cell apoptosis and heightened ROS levels. N-acetylcysteine (NAC) mitigated the cytotoxic effects and p38 phosphorylation. Furthermore, the knockdown of CaMKK2 in HSC-3 cells reduced cytotoxicity, ROS production, and p38 phosphorylation in response to CSE. Conclusion Our findings suggest that the CSE from both HTPs and traditional tobacco induce cytotoxicity. This toxicity is mediated by ROS, which are regulated through Ca.sup.2+ signaling and CaMKK2 pathways. Graphical Abstract Keywords: Heated tobacco products (HTPs), Calcium, Oral cancer, Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2), Reactive oxygen species (ROS), Author(s): Nagao Kagemichi[sup.1,2], Masanari Umemura[sup.1], Soichiro Ishikawa[sup.1,3], Yu Iida[sup.1,2], Shota Takayasu[sup.1], Akane Nagasako[sup.1], Rina Nakakaji[sup.1,3], Taisuke Akimoto[sup.2], Makoto Ohtake[sup.2], Takahiro Horinouchi[sup.4], Tetsuya Yamamoto[sup.2] and Yoshihiro Ishikawa[sup.1] Background Tobacco is responsible [...]

Recently, thermoplastic resins were used as matrix to synthesize carbon fiber‐reinforced thermoplastic (CFRTP) for recycling it easily. In this study, a CFRTP with excellent mechanical properties and heat resistance was synthesized using a polyether ether ketone (PEEK) as a matrix resin. The PEEK resin was modified to form cross‐linked structures through Friedel–Crafts reaction alkylation. The synthesis temperature of CFRTP was optimized considering the mechanical properties of PEEK, and its heat resistance was enhanced because of the cross‐linked structures. Further, the cross‐linked PEEK resin was partially used as a matrix resin, and the mechanical properties of the CFRTP were enhanced. We plan to develop a method for recycling CFRTP using PEEK and crosslinked PEEK for synthesizing C/C composites by focusing on the high heat resistance of the crosslinked PEEK containing a large amount of carbon and reducing mass loss after heat treatment. Highlights: CC bonds were introduced into the polyether ether ketone (PEEK) resin by Friedel–Crafts reaction alkylation.Thermal properties of PEEK were enhanced by hypercrosslinking reaction.Optimization of synthesized temperature was investigated to fabricate carbon fiber‐reinforced thermoplastic (CFRTP).Mechanical properties were enhanced CFRTP modified with hypercrosslinking reaction. [ABSTRACT FROM AUTHOR]

Application of physical forces, ranging from ultrasound to electric fields, is recommended in various clinical practice guidelines, including those for treating cancers and bone fractures. However, the mechanistic details of such treatments are often inadequately understood, primarily due to the absence of comprehensive study models. In this study, we demonstrate that an alternating magnetic field (AMF) inherently possesses a direct anti‐cancer effect by enhancing oxidative phosphorylation (OXPHOS) and thereby inducing metabolic reprogramming. We observed that the proliferation of human glioblastoma multiforme (GBM) cells (U87 and LN229) was inhibited upon exposure to AMF within a specific narrow frequency range, including around 227 kHz. In contrast, this exposure did not affect normal human astrocytes (NHA). Additionally, in mouse models implanted with human GBM cells in the brain, daily exposure to AMF for 30 min over 21 days significantly suppressed tumor growth and prolonged overall survival. This effect was associated with heightened reactive oxygen species (ROS) production and increased manganese superoxide dismutase (MnSOD) expression. The anti‐cancer efficacy of AMF was diminished by either a mitochondrial complex IV inhibitor or a ROS scavenger. Along with these observations, there was a decrease in the extracellular acidification rate (ECAR) and an increase in the oxygen consumption rate (OCR). This suggests that AMF‐induced metabolic reprogramming occurs in GBM cells but not in normal cells. Our results suggest that AMF exposure may offer a straightforward strategy to inhibit cancer cell growth by leveraging oxidative stress through metabolic reprogramming. [ABSTRACT FROM AUTHOR]

Background: Electronic gambling machines (EGMs) in gambling venues cause gambling-related harm and are a public health concern. This study focused on pachinko parlours as gambling venues and income-generating crimes as gambling-related harm. We aimed to verify whether income-generating crime rates increase in proximity to pachinko parlours and during the opening and post-closing periods of pachinko parlours relative to the pre-opening periods. Methods: We used crime records spanning 6.5 years, including data on the opening and closing days of pachinko parlours for 6.5 years. We also sampled the addresses of convenience stores, bowling alleys, and households with official land prices all over Japan. The dependent variable was the daily income-generating crime incidence rate. Areas within 0.5 km, 0.5–1 km, 1–5 km, and 5–10 km radii of the pachinko parlours were the independent variables. The pre-, opening-, and post-closing periods of the pachinko parlours were also independent variables. The covariates included the number of convenience stores and always open pachinko parlours near pachinko parlours. Data were analysed using an analysis of variance (ANOVA) and covariance (ANCOVA). We also used differences-in-differences analysis (DD) to reveal the increase in income-generating crime rates in neighbourhoods exposed to the opening or closing of pachinko parlours. Results: The daily income-generating crime incidence rate was significantly higher in areas within 0.5–1 km and 1–5 km radii of pachinko parlours than in those within 0.5 km and 5–10 km radii of them. The daily income-generating crime incidence rate was also significantly higher during the opening and post-closing periods than during the pre-opening period, even when controlling for the number of convenience stores and always open pachinko parlours. In particular, fraud crime rates increased with the opening and closing of pachinko parlours. Conclusions: The highest income-generating crime incidence rate was observed within a 0.5–1 km and 1–5 km radius of pachinko parlours. The opening of pachinko parlours also increased income-generating crime incidence rates, which increased after closing. Pachinko parlours are considered to be creating public harm because the corporate activities of these parlours make the youth in their neighbourhood perpetrators of fraud and older adults its victims. Future research should examine the current findings using official crime records. [ABSTRACT FROM AUTHOR]

Background: Various antigen‐presenting cells and tumor cells‐expressing PD‐L1 inhibits antitumor immune responses in the tumor microenvironment. Recently, numerous studies have shown that tumor cell intrinsic PD‐L1 also plays important roles in tumor growth and progression. On the other hand, oral squamous cell carcinoma (OSCC) cells overexpress epidermal growth factor receptor (EGFR) and EGFR signal pathway exacerbates tumor progression. Therefore, this study assessed whether tumor‐intrinsic PD‐L1 facilitates malignant potential of OSCC cells through regulation of EGFR signaling. Methods: Two OSCC cell lines, SAS and HSC‐3, were transfected with PD‐L1 and EGFR‐specific small interfering RNA (siRNA). Influences of PD‐L1 knockdown on malignant potentials of OSCC cells were examined by Cell Counting kit‐8 assay, transwell assay, sphere formation assay, flow cytometry, and Western blot. Effects of PD‐L1 and EGFR knockdown on each expression were examined by quantitative real‐time PCR (qRT‐PCR), Western blot, and flow cytometry. Results: Transfection of an PD‐L1‐siRNA into OSCC cells decreased the abilities of proliferation, stemness, and mobility of these cells significantly. PD‐L1 knockdown also decreased EGFR expression through the promotion of proteasome‐ and lysosome‐mediated degradation and following activation of the EGFR/protekin kinase B (AKT) signal pathway. Meanwhile, EGFR knockdown did not influence PD‐L1 expression in SAS and HSC‐3 cells, but treatment with a recombinant human EGF induced its expression. Treatment with erlotinib and cetuximab suppressed rhEGF‐induced PD‐L1 expression and localization in the cellular membrane of both OSCC cells. Conclusion: OSCC cells‐expressing PD‐L1 induced by EGF stimulation may promote malignancy intrinsically via the activation of the EGFR/AKT signaling cascade. [ABSTRACT FROM AUTHOR]

The article discusses the need for correction methods in the evaluation of structural metrics in brain imaging studies. Total intracranial volume (TIV) is a major factor affecting these metrics, and different correction methods have been used with varying results. A recent study evaluated four TIV correction methods and found that the proportion correction method had inconsistent results compared to the other three methods. The study highlights the importance of further research and comparisons with other correction approaches. Additionally, the article mentions the need to consider other sources of fluctuations in brain volume, such as physiological and technical factors, and the use of new brain atlases for quantitative measurements. [Extracted from the article]

AbstractBackgroundMaterials and MethodsResultsConclusionTakotsubo cardiomyopathy (TC) is a well-known complication of subarachnoid haemorrhage (SAH), often accompanied by neurogenic myocardial dysfunction. Although TC has been reported to be associated with higher morbidity and mortality among patients with aneurysmal SAH (aSAH), some patients have been reported to recover, the profiles and follow-up outcomes of these survivors remain unclear.To characterize the profiles of patients with aSAH complicated by TC who experienced favourable outcomes using long-term follow-up data, a consecutive series of patients with aSAH were enrolled and TC diagnosis was based on the revised version of the Mayo Clinic criteria. Clinical outcomes were assessed at 6 months according to modified Rankin Scale scores.Among 165 consecutive patients with aSAH, 15 cases were complicated by TC, corresponding to an occurrence rate of 9.0%. Five patients with aSAH complicated by TC (33.3%) experienced a favourable outcome, and the mean value of systolic blood pressure on arrival was significantly lower than in those who experienced an unfavourable outcome (p = 0.032).According to analysis, it is possible cardiac dysfunction with decreased cerebral perfusion pressure and catecholamine toxicity transiently worsens conscious disturbance in aSAH complicated by TC. Therefore, it is important to carefully screen patients with aSAH to identify those complicated by TC, and for close collaboration of the multidisciplinary team to design appropriate treatment strategies. [ABSTRACT FROM AUTHOR]

Aims: High uric acid (HUA)plays a significant role in the pathophysiology of cardiovascular disease. Studies have indicated that elevated uric acid levels can adversely affect cardiovascular health. Nevertheless, the impact of hyperuricemia on cardiomyopathy remains uncertain. Further research is needed to elucidate the relationship between HUA and cardiomyopathy, shedding light on its potential implications for heart health., Results: We demonstrated that Uox-KO mice accelerated the development of cardiomyopathy, causing significantly impaired cardiac function and myocardial fibrosis.Meanwhile, the mitochondrial morphology was destroyed, the lipid peroxidation products increased in number and the antioxidant function was weakened. In addition, we evaluated the effects of ferrostatin-1 (Fer-1), the ferroptosis inhibitor. Myocardial damage can be reversed by the Fer-1 treatment caused by HUA combined with DOX treatment. Benzbromarone, a uric acid-lowering drug, decreases myocardial fibrosis and ferroptosis by alleviating hyperuricemia in Uox-KO mice by DOX administration. In vitro, we observed that the activity of cardiomyocytes treated with HUA combined with DOX decreased significantly, and lipid reactive oxygen species (ROS) increased significantly. Afterward, we demonstrated that HUA could promote oxidative stress in DOX, characterized by increased mitochondrial ROS, and down-regulate protein levels of glutathione peroxidase 4 (GPX4). N-acetyl-L-cysteine, an antioxidant, inhibits the process by which HUA promotes DOX-induced ferroptosis by increasing the GPX4 expression., Innovation: We verified that HUA can exacerbate myocardial damage. This has clinical implications for the treatment of cardiac damage in patients with hyperuricemia., Conclusions: Our data suggested that HUA promotes cardiomyopathy. HUA promotes DOX-induced ferroptosis by increasing oxidative stress and down-regulating GPX4.

Background: Combining morphological and physiological evaluations might improve the risk stratification of patients who undergo percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) culprit lesions., Aims: We aimed to investigate the clinical utility of morphofunctional evaluation after PCI for identifying ACS patients with increased risk of subsequent clinical events., Methods: We retrospectively studied 298 consecutive ACS patients who had undergone optical coherence tomography (OCT)-guided PCI. We performed OCT-based morphological analysis and quantitative flow ratio (QFR)-based physiological assessment immediately after PCI. The non-culprit segment (NCS) was defined as the most stenotic untreated segment in the culprit vessel. The primary outcome was target vessel failure (TVF), a composite of cardiac death, target vessel-related myocardial infarction, and ischaemia-driven target vessel revascularisation., Results: During a median follow-up period of 990 days, 42 patients experienced TVF. Cox regression analysis revealed that the presence of thin-cap fibroatheroma (TCFA) in the NCS and a low post-PCI QFR, or the presence of TCFA in the NCS and a high ΔQFR in the NCS (QFR NCS ), were independently associated with TVF. The subgroup with TCFA in the NCS and a low post-PCI QFR had a significantly higher incidence of TVF (75%) than the other subgroups, and those with TCFA in the NCS and a high ΔQFR NCS had a significantly higher incidence of TVF (86%) than the other subgroups. The integration of TCFA in NCS, post-PCI QFR, and ΔQFR NCS with traditional risk factors significantly enhanced the identification of subsequent TVF cases., Conclusions: Combining post-PCI OCT and QFR evaluation may enhance risk stratification for ACS patients after successful PCI, particularly in predicting subsequent TVF.