The strong coupling between photons and phonons in polar materials gives rise to phonon-polaritons that encapsulate a wealth of physical information, offering crucial tools for the ultrafast terahertz sources and the topological engineering of terahertz light. However, it is still quite challenging to form and manipulate the terahertz phonon-polaritons under the ultrastrong coupling regime till now. In this work, we demonstrate the ultrastrong coupling between the phonon (at 0.95 THz) in a MaPbI3 film and the metallic bound states in the continuum (BICs) in Au metasurfaces. The Rabi splitting can be continuously tuned from 28% to 48.4% of the phonon frequency by adjusting the parameters (size, shape and period) of Au metasurfaces, reaching the ultrastrong coupling regime. By introducing wavelet transform, the mode evolution information of the terahertz phonon-polariton is successfully extracted. It indicates that the phonon radiation intensity of the MaPbI3 film is enhanced as the coupling strength is increased. This work not only establishes a new platform for terahertz devices but also opens new avenues for exploring the intricate dynamics of terahertz phonon-polaritons.
Background Neuroblastoma (NB), characterized by its marked heterogeneity, is the most common extracranial solid tumor in children. The status and functionality of mitochondria are crucial in regulating NB cell behavior. While the significance of mitochondria-related genes (MRGs) in NB is still missing in key knowledge. Materials and methods This study leverages consensus clustering and machine learning algorithms to construct and validate an MRGs-related signature in NB. Single-cell data analysis and experimental validation were employed to characterize the pivotal role of FEN1 within NB cells. Results MRGs facilitated the classification of NB patients into 2 distinct clusters with considerable differences. The constructed MRGs-related signature and its quantitative indicators, mtScore and mtRisk, effectively characterize the MRGs-related patient clusters. Notably, the MRGs-related signature outperformed MYCN in predicting NB patient prognosis and was adept at representing the tumor microenvironment (TME), tumor cell stemness, and sensitivity to the chemotherapeutic agents Cisplatin, Topotecan, and Irinotecan. FEN1, identified as the most contributory gene within the MRGs-related signature, was found to play a crucial role in the communication between NB cells and the TME, and in the developmental trajectory of NB cells. Experimental validations confirmed FEN1’s significant influence on NB cell proliferation, apoptosis, cell cycle, and invasiveness. Conclusion The MRGs-related signature developed in this study offers a novel predictive tool for assessing NB patient prognosis, immune infiltration, stemness, and chemotherapeutic sensitivity. Our findings unveil the critical function of FEN1 in NB, suggesting its potential as a therapeutic target.
Capsaicin (CAP) is the major pungent component of chili pepper and is being evaluated for use against numerous types of tumors. Although CAP is indicated to target multiple signaling pathways, exact mechanisms of how it disturb cancer cell metablism remain obscure. Recent studies revealed Sirtuin 1 (SIRT1) serves as a potential target of CAP in cancer cells, indicating a direct regulation of cancer cell histone acetylation by capsaicin. The present study evaluated the effect of CAP on gastric cancer (GC) cell lines to understand the mechanism of cell growth inhibition. The results showed that CAP could significantly suppress cell growth, while altering histone acetylation in GC cell lines. Further studies found that hMOF, a major histone acetyltranferase for H4K16, is central to CAP-induced epigenetic changes. Reduced hMOF activity was detected in GC tissues, which could be restored by CAP both in vivo and in vitro. These findings revealed an important role of hMOF-mediated histone acetylation in CAP-directed anti-cancer processes, and suggested CAP as a potential drug for use in gastric cancer prevention and therapy.
Aim: Small-cell lung cancer (SCLC) is usually diagnosed as an advanced stage with a poor outcome. SCLC has limited response to immunotherapy due to the absence or lack of immune cell infiltration, so studying its tumor immune microenvironment (TIME) is essential. Methods: The study involved patients with extensive-stage small-cell lung cancer (ES-SCLC) diagnosed at the Guangdong Lung Cancer Institute between January 2018 and April 2022 who had received the atezolizumab/carboplatin/etoposide (ECT) treatment. We used multi-immunohistochemistry (mIHC) to assess the prognostic value of YAP1 and TIME in SCLC, with results confirmed using public data. Results: 15 patients with sufficient baseline biopsy samples were included in this study. The total population of YAP1-positive cells is inversely related to progression-free survival (PFS) and shows a potential negative correlation with overall survival (OS). CD56-positive cells are the primary components of TIME in SCLC tumor parenchyma and stroma. The total population and cell density of YAP1-positive cells are significantly positively correlated with CD4-positive cells. Furthermore, in the tumor parenchyma, both the proportion and the cell density of YAP1-positive cells are positively correlated with that of FOXP3-positive cells. The total population of CD56-positive cells showed a negative correlation trend with YAP1-positive cells but without significant difference. Conclusion: YAP1 has shown prognostic value in SCLC patients receiving ECT regimen treatment. The high expression level of YAP1 seems related to the inhibitory TIME. However, some prospective studies with larger populations are warranted.
Purpose: This retrospective study aimed to evaluate the prognostic value of metabolic parameters in baseline fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for pediatric lymphoblastic lymphoma (LBL). Method: Thirty patients with LBL who underwent baseline 18F-FDG PET/CT from April 2013 to November 2018 were enrolled. Their metabolic parameters including maximum standardized uptake value (SUVmax), total metabolic tumor volume (TMTV), and total lesion glycolysis (TLG) were measured and compared with those from different clinical characteristic groups. Event-free survival (EFS) and overall survival (OS) curves were constructed using the Kaplan–Meier method and compared with the log-rank test. Results: The patients with stage Ⅳ had higher TMTV than stage Ⅲ (mean 580.66cm³ vs. 176.52cm³; p=0.031). No statistical significance in SUVmax and TLG was observed between patients with stages Ⅲ and Ⅳ (p=0.061; p=0.291). After a median follow-up of 41.5 months (range of 1–86 months), the patients with a low TMTV (<242.91cm³) had better 3-year EFS rate compared with those with a high TMTV (88.9% vs. 56.3%; p=0.036). However, SUVmax and TLG were not predictive of EFS(p=0.874; p=0.152). Conclusions: TMTV may be a potential PET/CT metabolic parameter for predicting the prognosis of pediatric lymphoblastic lymphoma. A high TMTV indicates a poor outcome. However, SUVmax and TLG are not related to the prognosis of pediatric lymphoblastic lymphoma.
Background: Continuous damage from oxidative stress and apoptosis are the important mechanisms that facilitate chronic heart failure (CHF). Molecular hydrogen (H2) has potentiality in the aspects of anti-oxidation. The objectives of this study were to investigate the possible mechanism of H2 inhalation in delaying the progress of CHF. Methods and Results: A total of 60 Sprague-Dawley (SD) rats were randomly divided into four groups: Sham, Sham treated with H2, CHF and CHF treated with H2. Rats from CHF and CHF treated with H2 groups were injected isoprenaline subcutaneously to establish the rat CHF model. One month later, the rat with CHF was identified by the echocardiography. After inhalation of H2, cardiac function was improved vs. CHF (p < 0.05), whereas oxidative stress damage and apoptosis were significantly attenuated (p < 0.05). In this study, the mild oxidative stress was induced in primary cardiomyocytes of rats, and H2 treatments significantly reduced oxidative stress damage and apoptosis in cardiomyocytes (p < 0.05 or p < 0.01). Finally, as a pivotal transcription factor in reactive oxygen species (ROS)-apoptosis signaling pathway, the expression and phosphorylation of p53 were significantly reduced by H2 treatment in this rat model and H9c2 cells (p < 0.05 or p < 0.01). Conclusion: As a safe antioxidant, molecular hydrogen mitigates the progression of CHF via inhibiting apoptosis modulated by p53. Therefore, from the translational point of view and speculation, H2 is equipped with potential therapeutic application as a novel antioxidant in protecting CHF in the future.
Background Intravoxel incoherent motion (IVIM) can provide quantitative information about water diffusion and perfusion that can be used to evaluate hepatic injury, but it has not been studied in hepatic injury induced by intestinal ischemia–reperfusion (IIR). Dynamic contrast‐enhanced (DCE) magnetic resonance imaging (MRI) can provide perfusion data, but it is unclear whether it can provide useful information for assessing hepatic injury induced by IIR. Purpose To examine whether IVIM and DCE‐MRI can detect early IIR‐induced hepatic changes, and to evaluate the relationship between IVIM and DCE‐derived parameters and biochemical indicators and histological scores. Study Type Prospective pre‐clinical study. Population Forty‐two male Sprague–Dawley rats. Field Strength/Sequence IVIM‐diffusion‐weighted imaging (DWI) using diffusion‐weighted echo‐planar imaging sequence and DCE‐MRI using fast spoiled gradient recalled‐based sequence at 3.0 T. Assessment All rats were randomly divided into the control group (Sham), the simple ischemia group, the ischemia–reperfusion (IR) group (IR1h, IR2h, IR3h, and IR4h) in a model of secondary hepatic injury caused by IIR, and IIR was induced by clamping the superior mesenteric artery for 60 minutes and then removing the vascular clamp. Advanced Workstation (AW) 4.6 was used to calculate the imaging parameters (apparent diffusion coefficient [ADC], true diffusion coefficient [ D ], perfusion‐related diffusion [ D * ] and volume fraction [ f ]) of IVIM. OmniKinetics (OK) software was used to calculate the DCE imaging parameters ( K trans , K ep , and V e ). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed with an automatic biochemical analyzer. Superoxide dismutase (SOD) activity was assessed using the nitro‐blue tetrazolium method. Malondialdehyde (MDA) was determined by thiobarbituric acid colorimetry. Histopathology was performed with hematoxylin and eosin staining. Statistical Tests One‐way analysis of variance (ANOVA) and Bonferroni post‐hoc tests were used to analyze the imaging parameters and biochemical indicators among the different groups. Pearson correlation analysis was applied to determine the correlation between imaging parameters and biochemical indicators or histological score. Results ALT and MDA reached peak levels at IR4h, while SOD reached the minimum level at IR4h (all P < 0.05). ADC, D , D * , and f gradually decreased as reperfusion continued, and K trans and V e gradually increased (all P < 0.05). The degrees of change for f and V e were greater than those of other imaging parameters at IR1h (all P < 0.05). All groups showed good correlation between imaging parameters and SOD and MDA ( r [ADC] = 0.615, −0.666, r [ D ] = 0.493, −0.612, r [ D * ] = 0.607, −0.647, r [ f ] = 0.637, −0.682, r [ K trans ] = −0.522, 0.500, r [ V e ] = −0.590, 0.665, respectively; all P < 0.05). However, the IR groups showed poor or no correlation between the imaging parameters and SOD and MDA ( P [ K trans and MDA] = 0.050, P [ D and SOD] = 0.125, P [the remaining imaging parameters] < 0.05). All groups showed a positive correlation between histological score and K trans and V e ( r = 0.775, 0.874, all P < 0.05), and a negative correlation between histological score and ADC, D , f , and D * ( r = −0.739, −0.821, −0.868, −0.841, respectively; all P < 0.05). For the IR groups, there was a positive correlation between histological score and K trans and V e ( r = 0.747, 0.802, all P < 0.05), and a negative correlation between histological score and ADC, D , f , and D * ( r = −0.567, −0.712, −0.715, −0.779, respectively; all P < 0.05). Data Conclusion The combined application of IVIM and DCE‐MRI has the potential to be used as an imaging tool for monitoring IIR‐induced hepatic histopathology. Level of Evidence 1 Technical Efficacy Stage 2
Galectin-9 (Gal-9), a member of the β-galactoside-binding galectin family, plays a role in immune response, apoptosis, cell proliferation and cell death. Recent studies have shown that abnormal expression of Gal-9 is involved in certain primary cancers. The present study is the first investigation of the role of Gal-9 gene expression in clinically diagnosed primary gastric cancer tissues. Gal-9 mRNA expression was assessed in 44 clinically diagnosed frozen primary cancer tissue samples using quantitative PCR (qPCR). Analysis of the qPCR data revealed a significant reduction (>2-fold decreased) of Gal-9 gene expression in gastric cancer tissues in 77% (34/44) of patients. In patients with gastric cancer, although no statistically significant difference was found between adjacent (<2 cm away from the cancer tissue) and normal tissues (>5 cm away from the cancer tissue), a >2-fold reduction in Gal-9 expression was observed in the adjacent tissues of 34% of the patients. Compared to matched normal or adjacent tissues, the gene expression of Gal-9 was significantly decreased in tumor tissues (p<0.001). The correlation of Gal-9 expression and clinicopathological features in gastric cancer was analyzed according to the TNM classification system using AJCC stage grouping. In patients with gastric cancer, clinical staging, tumor pathological stage (pT stage), tumor cell differentiation, lymph node metastasis and survival rate were found to be associated with Gal-9 expression. However, no significant association was found between Gal-9 expression and distant metastasis (p>0.05). No significant difference was found between patients of different genders, levels of cell differentiation, distant metastasis status or different survival time of patients. Compared to normal tissues, >2-fold reduction of Tim-3 expression in gastric cancer tissues occurred in 59% of patients, but no correlation was found between Gal-9 and Tim-3 in gastric cancer. These results strongly suggest that Gal-9 is involved in tumorigenesis of gastric cancer.
Abstract Background Various types of medical glues/adhesives/topical coagulants’ (referred to as MG hereinafter) have widespread application as surgical adhesives, and have been shown to be safe and effective for a broad range of usage, such as in hemostasis, reinforcement of intestinal anastomoses or sites of potential fluid leakage, adhesion of two surfaces, wound closure, and vascular embolization. However, inappropriate application of MG may sometimes lead to serious complications. Herein, we describe three cases of serious postoperative complications induced by a possible inappropriate use of N-butyl-2-cyanoacrylate MG (NBCA MG). Case presentation Three patients presented with abdominal pain (chronic pain in cases 1 and 2, and acute pain in Case 3), hematochezia (Case 2), and intestinal obstruction (Case 3). All patients had a history of abdominal surgery and intraoperative use of NBCA MG. Abdominal computed tomography and gastroenterological endoscopy revealed foreign bodies (solidified MG in cases 1 and 2) and intestinal obstruction related to a mass of residual non-absorbed MG causing an internal hernia from a dense adhesion (Case 3). All patients underwent exploratory laparotomy, which revealed duodenal perforation, colonic erosion, and an internal hernia, all of which was related to MG use. We undertook removal of the foreign bodies (cases 1 and 2), surgical closure of the site of duodenal erosion (Case 1), partial colectomy (Case 2), and partial enterectomy (Case 3). Conclusion Inappropriate application of MG may induce serious complications. We emphasize the importance of careful evaluation of the indications, dosage, and spraying thickness of MG in clinical practice. Serious complications caused by inappropriate application of MG should be reported to raise awareness in the surgical fraternity.
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