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Accumulation of senescent cells is a recognized feature in hepatocellular carcinoma (HCC), but their specific types and prognostic implications remain under investigation. This study aimed to delineate senescent cell types and their senescent patterns in HCC using publicly available bulk and single-cell mRNA sequencing data. Through gene expression and gene set enrichment analysis, we identified distinct senescent patterns within HCC samples. Notably, unconventional T cells, specifically natural killer T cells and γδT cells, were found to be the predominant senescent cell types. These cells exhibited enriched pathways related to DNA damage, senescence and the negative regulation of lymphocyte activation. Furthermore, we observed upregulation of the mTOR signaling pathway, which correlated positively with the expression of senescence-associated genes. This suggests a potential regulatory role for mTOR in the senescence of HCC. Strikingly, patients with elevated expression of senescence markers, including p16INK4A, p21, and GLB1, demonstrated significantly reduced overall survival rates. Our findings indicate that immunosenescence in unconventional T cells may play a role in HCC progression. The potential therapeutic implications of targeting the mTOR pathway or eliminating senescent unconventional T cells warrant further exploration to improve HCC patient outcomes.
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BACKGROUND: Electronic foetal monitoring (EFM), a method to monitor foetal intrauterine conditions and foetal reserve capacity, is the most extensively used intrauterine monitoring technology in obstetrics. OBJECTIVE: This study aims to compare the Thoth wearable foetal electrocardiogram (foetal ECG [FECG]) monitoring system with a traditional Doppler foetal heart monitoring system before labour to investigate their respective values in clinical application. METHODS: A total of 393 pregnant women admitted to our hospital between 2020 and 2022 participated in this study. They were recruited using the convenience sampling method. We employed a paired design to assess the confusion rate, trend overlap, and foetal heart rate/ECG monitoring consistency, whereas a completely randomised design was used to measure pregnancy outcome indicators. The participants were divided into two groups using a random number table: the Thoth group (n= 196) and the traditional Doppler group (n= 197). Each group was monitored using the corresponding system. RESULTS: The Thoth monitor demonstrated a lower confusion rate compared with the traditional Doppler monitor (0.25% vs 2.04%; χ2= 5.508, P= 0.019). The trend overlap in foetal heart rates was consistently 100%, with 91.2% of readings showing a consistency rate of ⩾ 95%. Additionally, the Thoth monitor recorded a higher cumulative interruption time in the foetal heart rate curve (12.13 ± 2.22 vs 21.02 ± 2.34; t= 18.471, P< 0.001) and more abnormal ECGs (21.21 ± 4.32 vs 18.21 ± 2.91; t= 7.582, P< 0.001) than the traditional Doppler system. CONCLUSION: The Thoth wearable FECG monitor offers several advantages over the traditional Doppler foetal heart monitoring system. These include a reduced confusion rate, more accurate data collection, a lower rate of clinical misjudgement, reduced workload for medical staff, and enhanced comfort during vaginal delivery. The rates of emergency caesarean sections and neonatal asphyxia in the Thoth group were marginally lower than those in the Doppler group, which may be attributed to issues such as ECG disconnection or interference from the maternal heart rate.
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The size of liposomal drugs has been demonstrated to strongly correlate with their pharmacokinetics and pharmacodynamics. While the microfluidic method successfully achieves the production of liposomes with well-controlled sizes across various buffer/lipid flow rate ratio (FRR) settings, any adjustments to the FRR inevitably influence the concentration, encapsulation efficiency (EE), and stability of liposomal drugs. Here we describe a controllable cavitation-on-a-chip (CCC) strategy that facilitates the precise regulation of liposomal drug size at any desired FRR. The CCC-enabled size-specific liposomes exhibited striking differences in uptake and biodistribution behaviors, thereby demonstrating distinct antitumor efficacy in both tumor-bearing animal and melanoma patient-derived organoid (PDO) models. Intriguingly, as the liposome size decreased to approximately 80 nm, the preferential accumulation of liposomal drugs in the liver transitioned to a predominant enrichment in the kidneys. These findings underscore the considerable potential of our CCC approach in influencing the pharmacokinetics and pharmacodynamics of liposomal nanomedicines.
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Dispositivos Laboratorio en un Chip , Liposomas , Liposomas/química , Animales , Humanos , Ratones , Distribución Tisular , Tamaño de la Partícula , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/administración & dosificación , Línea Celular Tumoral , Melanoma/tratamiento farmacológico , Melanoma/patologíaRESUMEN
The development of high-temperature nondestructive testing (NDT) requires ultrasonic transducers with good temperature resistance and high sensitivity for improved detection efficiency. Piezoelectric composite can improve the performance of transducers because of its high electromechanical coupling coefficient and adjustable acoustic impedance. In this study, 1-3-2 composites and 1-3-2 high-temperature composite ultrasonic transducers (HTCUTs) based on 0.36BiScO3-0.64PbTiO3 (BSPT), which is preferred piezoelectric materials at 200 ° C- 300 ° C, and high-temperature epoxy with a center frequency of 6 MHz were designed and fabricated. From 25 ° C to 250 ° C, 1-3-2 composites show a higher electromechanical coupling coefficient kt especially at high temperatures (~0.53 at 25 ° C and ~0.64 at 250 ° C) than monolithic BSPT (~0.5). The signal of the pulse-echo response of 1-3-2 HTCUTs is distinguishable up to 250 ° C and remains stable ( [Formula: see text] mV) below 150 ° C, exhibiting higher sensitivity (improved by 7 dB) than that of monolithic BSPT high-temperature ultrasonic transducers (HTUTs). Bandwidth has been greatly enhanced especially at high temperatures (~103% at 250 ° C) compared with that of monolithic BSPT HTUTs (~30% at 250 ° C). To verify the excellent performance, B-mode scanning imaging measurement of a stepped steel block and defect location detection of a steel block was performed, showing the potential for high-temperature NDT applications.
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Optical imaging and phototherapy in deep tissues face notable challenges due to light scattering. We use encoded acoustic holograms to generate three-dimensional acoustic fields within the target medium, enabling instantaneous and robust modulation of the volumetric refractive index, thereby noninvasively controlling the trajectory of light. Through this approach, we achieved a remarkable 24.3% increase in tissue heating rate in vitro photothermal effect tests on porcine skin. In vivo photoacoustic imaging of mouse brain vasculature exhibits an improved signal-to-noise ratio through the intact scalp and skull. These findings demonstrate that our strategy can effectively suppress light scattering in complex biological tissues by inducing low-angle scattering, achieving an effective depth reaching the millimeter scale. The versatility of this strategy extends its potential applications to neuroscience, lithography, and additive manufacturing.
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Técnicas Fotoacústicas , Ratones , Animales , Porcinos , Técnicas Fotoacústicas/métodos , Fototerapia , Cráneo , Acústica , RefractometríaRESUMEN
Background: Sclerosing adenosis (SA) is a common proliferative benign lesion without atypia in the breast that may mimic invasive ductal carcinoma (IDC) on medical imaging, leading to it often being misdiagnosed and mistreated. Consequently, the purpose of this study was to assess the diagnostic value of multimodal ultrasound imaging in distinguishing SA from IDC. Methods: Multimodal ultrasound imaging, including automated breast volume scan (ABVS), elasticity imaging (EI), and color Doppler flow imaging (CDFI), were performed on 120 consecutive patients comprising 122 breast lesions (54 SA, 68 IDC). All lesions were pathologically confirmed. Multimodal ultrasound imaging features were compared between the two groups. Binary logistic regression analysis based on ABVS, EI, and CDFI was conducted to formulate a logistic regression equation for differentiating SA from IDC. The diagnostic performances of ABVS, EI, CDFI, and their combination were compared by the receiver operating characteristic (ROC) curve analysis. Results: The sensitivity, specificity, and accuracy of ABVS, EI, CDFI, and their combination in differentiating SA from IDC were, respectively, 75.00%, 72.22%, and 73.77%; 86.76%, 72.22%, and 80.33%; 73.53%, 64.81%, and 69.67%; and 88.24%, 74.07%, and 81.97%. Combining multimodal ultrasound imaging yielded an area under the curve (AUC) of 0.895 (95% confidence interval: 0.827-0.943), which was higher than that of ABVS, EI, and CDFI, with AUC values of 0.736, 0.795, and 0.692, respectively, and the difference was statistically significant (ABVS vs. combined model, P<0.001; CDFI vs. combined model, P<0.001; EI vs. combined model, P<0.001). There was no significant difference in the diagnostic efficacy among the three imaging modalities (ABVS vs. EI, P=0.266; ABVS vs. CDFI, P=0.4671; EI vs. CDFI, P=0.051). Compared with those in IDC, the calcification (16.67% vs. 57.35%; P<0.001) and retraction phenomena in the coronal planes (18.52% vs. 57.35%; P<0.001) were less common in patients with SA, while circumscribed margin (38.89% vs. 5.88%; P<0.001), vascularity grade 0-I (64.81% vs. 26.47%; P<0.001), and elasticity scores 1-3 (72.22% vs. 13.24%; P<0.001) were more frequently found in patients with SA. Patients with SA were significantly younger than were patients with IDC (43±11 vs. 54±11 years; P<0.001), and the lesion size was smaller in patients with SA than in those with IDC (median size 1.0 cm; interquartile range (IQR), 0.9 cm vs. median size 1.3 cm; IQR, 1.3 cm; P<0.001). Conclusions: The preliminary results suggested that multimodal ultrasound imaging can improve the diagnostic accuracy of SA and provide additional information for differential diagnosis of SA and IDC.