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Bone is a major tissue for uranium deposition in human body. Considering mesenchymal stem cells (MSCs) play a vital role in bone formation and injury recovery, studying the mechanism of MSCs responding to uranium poisoning can benefit the understanding of bone damage and repair after uranium exposure. Cellular structural alterations were analyzed via transmission electron microscopy (TEM). Changes in cellular behaviors were assessed through cellular viability, apoptosis, and the production of DNA double-strand breaks (DSBs). In addition, the influence of gap junctional intercellular communication (GJIC) on uranium toxicity was assessed. The disruption of MSCs was elevated with the increase in uranyl nitrate concentration, as shown by TEM micrograph. This was verified by the results of cellular viability and DSB production. Interestingly, the results of apoptosis assay indicated significant apoptosis occurred, which was accompanied with an obvious disruption of cellular membranes. Furthermore, closely contacted cell confluence groups exhibited resistant to uranium poisoning in contrast to sparse growth groups, which can be eliminated with the pretreatment of a GJIC inhibitor in the close connection group. To verify the association between GJIC and cytotoxic effects of uranyl nitrate, GJIC function was evaluated by wound healing and cellular migration. The results showed an inhibition of the healing ratio and migration ability induced by the exposure of uranyl nitrate. The low transfer efficiency of the dye coupling experiment and depressed expression of gap functional protein connexins confirmed the impairment of GJIC function. These results suggest that uranium toxicity is involved with GJIC dysfunction.
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The effects of tritium at low doses and low dose rates have received increasing attention due to recent developments in fusion energy and the associated risks of tritium releases into the environment. Mitochondria have been identified as a potential candidate for studying the effects of low-dose/low-dose-rate radiation, with extensive experimental results obtained using X-ray irradiation. In this study, irradiation experiments were conducted on normal B-lymphoblastoid cells using HTO at varying doses. When compared to X-ray irradiation, no significant differences in cell viability induced by different doses were observed. However, the results of ATP levels showed a significant difference between the irradiated sample at a dose of 500 mGy by tritium beta-rays and the sham-irradiated sample, while the levels obtained with X-ray irradiation were almost identical to the sham-irradiated sample. In contrast, ATP levels for both tritium beta-rays and X-rays at a dose of 1.0 Gy showed minimal differences compared to the sham-irradiated sample. Furthermore, distinct effects at 500 mGy were also confirmed in both ROS levels and apoptosis results obtained through tritium beta-ray irradiation. This suggests that mitochondria might be a potential sensitive target for investigating the effects of tritium beta-ray irradiation.
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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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Cervical cancer (CC), as a common female malignant tumor in the world, is an important risk factor endangering women's health worldwide. The purpose of this study was to investigate the role of RBM15 in CC. The TCGA database was used to screen differentially expressed m6A genes in normal and tumor tissues. QRT-PCR was used to quantify HEIH, miR-802, EGFR, cell stemness, and epithelial-mesenchymal transition (EMT)-related genes. The interaction between HEIH and miR-802 was verified by dual-luciferase reporter assay and RIP assay. The occurrence of tumor cells after different treatments was detected by CCK-8, transwell and EdU staining. BALB/c nude mice were used to examine the effects of different treatments on tumor growth and cell stemness in vivo. RBM15 was upregulated in tumor tissues and cells. M6A was highly enriched in HEIH and enhances its RNA stability. HEIH acts as an oncogenic lncRNA to promote CC cell proliferation, migration and tumor growth. Mechanistically, HEIH regulates tumor cell stemness and promotes the proliferation and migration of CC cells by competitively adsorbing miR-802 and up-regulating the expression of EGFR. In short, our data shown that the m6A methyltransferase RBM15 could affect tumor cell proliferation, metastasis and cell stemness by stabilizing HEIH expression.
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Adenina/análogos & derivados , MicroARNs , ARN Largo no Codificante , Neoplasias del Cuello Uterino , Animales , Ratones , Humanos , Femenino , MicroARNs/genética , MicroARNs/metabolismo , Línea Celular Tumoral , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias del Cuello Uterino/patología , Ratones Desnudos , Receptores ErbB/genética , Receptores ErbB/metabolismo , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica/genética , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismoRESUMEN
Ultra-high frequency (>100 MHz) acoustic waves feature biocompatibility and high sensitivity and allow biomedical imaging and acoustic tweezers. Primarily, excellent spatial resolution and broad bandwidth at ultra-high frequency is the goal for pathological research and cell selection at the cellular level. Here, we propose an efficient approach to visualize mouse brain atrophy by self-focused ultrasonic sensors at ultra-high frequency with ultra-broad bandwidth. The numerical models of geometry and theoretically predicted acoustic parameters for half-concave piezoelectric elements are calculated by the differential method, which agrees with measured results (lateral resolution: 24 µm, and bandwidth: 115% at -6 dB). Compared with the brain slices of 2-month-old mouse, the atrophy visualization of the 6-month-old mouse brain was realized by C-mode imaging with an acoustic microscopy system, which is a potential prospect for diagnosis and treatment of Alzheimer's disease (AD) combined with neuroscience. Meanwhile, the acoustic properties of the brain slices were quantitatively measured by the acoustic microscopy. These encouraging results demonstrate the promising application for high-resolution imaging in vitro biological tissue with ultra-high frequency self-focusing ultrasonic sensors.
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Diagnóstico por Imagen , Ultrasonido , Ratones , Animales , Acústica , Encéfalo/diagnóstico por imagen , AtrofiaRESUMEN
Protein degraders are currently under rapid development as a promising modality for drug discovery. They are compounds that orchestrate interactions between a target protein and an E3 ubiquitin ligase, prompting intracellular protein degradation through proteasomal pathway. More protein degraders identification will greatly promote the development of this field. BAG3 is widely recognized as an excellent therapeutic target in cancer treatments. Exploring protein degraders that target BAG3 degradation has profound implications. Herein, molecular docking was applied to assess binding energy between 81 clinical phase I kinase inhibitors and BAG3. BAG3 protein and mRNA level were detected by western blot and quantitative real-time PCR. CCK8 assay and colony formation assay were applied to detect the cell viability and proliferation rate. Cell death was accessed using flow cytometry combined with PI and Annexin V double staining. AZD7762, a Chk1 kinase inhibitor, was identified to induce BAG3 degradation in a ubiquitin-proteasome pathway. AZD7762-induced BAG3 degradation was not dependent on Chk1 expression or activity. CRBN, an E3 ligase, was identified to bind to BAG3 and mediated BAG3 ubiquitination in the presence of AZD7762. By targeting Chk1 and BAG3, two ideal therapeutic targets in cancer treatment, AZD7762 would be a powerful chemotherapy agent in the future.
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Complejo de la Endopetidasa Proteasomal , Ubiquitina-Proteína Ligasas , Humanos , Complejo de la Endopetidasa Proteasomal/metabolismo , Línea Celular Tumoral , Simulación del Acoplamiento Molecular , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinas/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Reguladoras de la Apoptosis/metabolismoRESUMEN
Cuproptosis can serve as potential prognostic predictors in patients with cancer. However, the role of this relationship in ovarian serous cystadenocarcinoma (OV) remains unclear. 376 OV tumor samples were obtained from the Cancer Genome Atlas (TCGA) database, and long non-coding RNAs (lncRNAs) related to cuproptosis were obtained through correlation analysis. The risk assessment model was further constructed by univariate Cox regression analysis and LASSO Cox regression. Bioinformatics was used to analyze the regulatory effect of relevant risk assessment models on tumor mutational burden (TMB) and immune microenvironment. We obtained 5 lncRNAs (AC025287.2, AC092718.4, AC112721.2, LINC00996, and LINC01639) and incorporated them into the Cox proportional hazards model. Kaplan-Meier (KM) curve analysis of the prognosis found that the high-risk group was associated with a poorer prognosis. The receiver operating characteristic (ROC) curve showed stronger predictive power compared to other clinicopathological features. Immune infiltration analysis showed that high-risk scores were inversely correlated with CD8+ T cells, CD4+ T cells, macrophages, NK cells, and B cells. Functional enrichment analysis found that they may act via the extracellular matrix (ECM)-interacting proteins and other pathways. We successfully constructed a reliable cuproptosis-related lncRNA model for the prognosis of OV.
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Cistadenocarcinoma Seroso , Neoplasias Ováricas , ARN Largo no Codificante , Femenino , Humanos , ARN Largo no Codificante/genética , Cistadenocarcinoma Seroso/genética , Pronóstico , Carcinoma Epitelial de Ovario , Inmunoterapia , Neoplasias Ováricas/genética , Microambiente TumoralRESUMEN
RNase P is the essential activity that performs the 5' maturation of transfer RNA (tRNA) precursors. Beyond the ancestral form of RNase P containing a ribozyme, protein-only RNase P enzymes termed PRORP were identified in eukaryotes. In human mitochondria, PRORP forms a complex with two protein partners to become functional. In plants, although PRORP enzymes are active alone, we investigate their interaction network to identify potential tRNA maturation complexes. Here we investigate functional interactions involving the Arabidopsis nuclear RNase P PRORP2. We show, using an immuno-affinity strategy, that PRORP2 occurs in a complex with the tRNA methyl transferases TRM1A and TRM1B in vivo. Beyond RNase P, these enzymes can also interact with RNase Z. We show that TRM1A/TRM1B localize in the nucleus and find that their double knockout mutation results in a severe macroscopic phenotype. Using a combination of immuno-detections, mass spectrometry and a transcriptome-wide tRNA sequencing approach, we observe that TRM1A/TRM1B are responsible for the m22G26 modification of 70% of cytosolic tRNAs in vivo. We use the transcriptome wide tRNAseq approach as well as RNA blot hybridizations to show that RNase P activity is impaired in TRM1A/TRM1B mutants for specific tRNAs, in particular, tRNAs containing a m22G modification at position 26 that are strongly downregulated in TRM1A/TRM1B mutants. Altogether, results indicate that the m22G-adding enzymes TRM1A/TRM1B functionally cooperate with nuclear RNase P in vivo for the early steps of cytosolic tRNA biogenesis.
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Proteínas de Arabidopsis , Arabidopsis , Humanos , Arabidopsis/metabolismo , Ribonucleasa P/genética , Ribonucleasa P/química , Ribonucleasa P/metabolismo , Proteínas de Arabidopsis/metabolismo , ARN de Transferencia/genética , ARN de Transferencia/metabolismo , Procesamiento Postranscripcional del ARNRESUMEN
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological entity characterized by intrahepatic ectopic steatosis. As a consequence of increased consumption of high-calorie diet and adoption of a sedentary lifestyle, the incidence of NAFLD has surpassed that of viral hepatitis, making it the most common cause of chronic liver disease globally. Huangqin decoction (HQD), a Chinese medicinal formulation that has been used clinically for thousands of years, has beneficial outcomes in patients with liver diseases, including NAFLD. However, the role and mechanism of action of HQD in lipid metabolism disorders and insulin resistance in NAFLD remain poorly understood. AIM: To evaluate the ameliorative effects of HQD in NAFLD, with a focus on lipid metabolism and insulin resistance, and to elucidate the underlying mechanism of action. METHODS: High-fat diet-induced NAFLD rats and palmitic acid (PA)-stimulated HepG2 cells were used to investigate the effects of HQD and identify its potential mechanism of action. Phytochemicals in HQD were analyzed by high-performance liquid chromatography (HPLC) to identify the key components. RESULTS: Ten primary chemical components of HQD were identified by HPLC analysis. In vivo, HQD effectively prevented rats from gaining body and liver weight, improved the liver index, ameliorated hepatic histological aberrations, decreased transaminase and lipid profile disorders, and reduced the levels of pro-inflammatory factors and insulin resistance. In vitro studies revealed that HQD effectively alleviated PA-induced lipid accumulation, inflammation, and insulin resistance in HepG2 cells. In-depth investigation revealed that HQD triggers Sirt1/NF-κB pathway-modulated lipogenesis and inflammation, contributing to its beneficial actions, which was further corroborated by the addition of the Sirt1 antagonist EX-527 that compromised the favorable effects of HQD. CONCLUSION: In summary, our study confirmed that HQD mitigates lipid metabolism disorders and insulin resistance in NAFLD by triggering the Sirt1/NF-κB pathway.
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Resistencia a la Insulina , Trastornos del Metabolismo de los Lípidos , Enfermedad del Hígado Graso no Alcohólico , Animales , Ratas , FN-kappa B , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/etiología , Scutellaria baicalensis , Metabolismo de los Lípidos , Sirtuina 1 , Inflamación , LípidosRESUMEN
As a replacement for highly flammable and volatile organic liquid electrolyte, solid polymer electrolyte shows attractive practical prospect in high-energy lithium metal batteries. However, unsatisfied interface performance and ionic conductivities are two critical challenges. A common strategy involves introducing organic solvents or plasticizers, but this violates the original intention of security design. Here, an electrolyte concept called liquid polymer electrolyte without any small molecular solvents is proposed for safe and high-performance batteries, based on the design of a room-temperature liquid-state brush-like polymer as the sole solvent of lithium salts. This liquid polymer electrolyte is non-flammable and exhibits high ionic conductivity (1.09 [Formula: see text] 10-4 S cm-1 at 25 °C), significant lithium dendrite suppression, and stable long-term cycling over a wide operating temperature range ( ≥ 1000 cycles at 60 °C and 90 °C). Moreover, the pouch cell can resist thermal abuse, vacuum environment, and mechanical abuse. This electrolyte and design strategy are expected to provide enlightening ideas for the development of safe and high-performance polymer electrolytes.
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Sleep is an extremely important physiological state to maintain human life. Sleep disorders can not only cause anxiety and depression, but also induce multi-system diseases that seriously affect brain function and physical health. The neuroinflammation is a key pathological process after sleep disorders, which can induce a series of nervous system diseases. In recent years, the role of microglia activation in neuroinflammation has been paid more and more attention and become a research hotspot in this field. The imbalance of the central microenvironment after sleep disorders leads to changes in the activation and polarization of microglia, which triggers neuroinflammatory response. The activation and polarization of microglia in the sleep disorders are regulated by multiple signaling pathways and complex molecular mechanisms. This paper summarizes five signaling pathways of microglia activation in central inflammation induced by sleep disorders, including P2X7 receptor (P2X7R), p38MAPK, Toll-like receptor 4 (TLR4)/NF-κB, JAK/STAT, and α7 nicotinic acetylcholine receptor (α7-nAChR) pathways, in order to provide reference for further research and clinical treatment targets selection of sleep disorders.
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Enfermedades Neuroinflamatorias , Trastornos del Sueño-Vigilia , Humanos , Microglía/metabolismo , Transducción de Señal/fisiología , FN-kappa B/metabolismo , Inflamación/metabolismo , Trastornos del Sueño-Vigilia/metabolismoRESUMEN
BACKGROUND: Clinical decision-making involves ethical issues that become more and more complex. Nurse interns must be more skilled in making rational and timely decisions when facing ethical dilemmas. The contributing factors and their relationships that challenge ethical decision-making among nurse interns must be fully understood, as this level of knowledge can support the development of strategies and interventions that improve the ethical decision-making ability of nurse interns. OBJECTIVE: This study examined the relationships between moral courage, moral sensitivity, and ethical decision-making by nurse interns. In addition, we investigated whether moral sensitivity mediates the relationship between moral courage and ethical decision-making. DESIGN: A descriptive cross-sectional study using an online questionnaire. SETTING: The study sampled nurse interns from Class iii Grade A general hospitals in Sichuan Province, China. PARTICIPANTS: A convenience sampling method was used to select 1334 nurse interns from March 2022 to May 2022. METHODS: A general information questionnaire, the Nurses' Moral Courage Scale (NMCS), the Chinese Moral Sensitivity Questionnaire (MSQ), and the Judgement About Nursing Decision (JAND) were used for data collection. Data was processed and analysed using SPSS 26.0 and Amos 28.0. Data analysis included descriptive statistics, Pearson correlation analysis, and structural equation modelling. RESULTS: Moral courage was found to be positively correlated with ethical decision-making (P < 0.01). Moral sensitivity was also positively correlated with ethical decision-making (P < 0.01) and had a mediating effect on the relationship between moral courage and ethical decision-making (P < 0.01). CONCLUSIONS: The moral courage and moral sensitivity of nurse interns are positively correlated with ethical decision-making ability. Moral sensitivity significantly mediates the relationship between moral courage and ethical decision-making ability. The knowledge gained from this study can inform educational strategies and interventions in supporting the development of nurse interns' ethical decision-making ability.
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Volatile compounds including terpenes, aldehyde, phenol, and alcohol are significantly contributed floral and fruity aromas to the Muscat variety. 'Ruidu Hongyu' grapevine is one of the newly developed grape varieties, and cultivation of this variety has been extended across China due to unique quality traits and taste. In this study, HS-SPME/GC-MS and transcriptome sequencing analysis were performed to evaluate the impact of exogenous 2,4-epibrassinolide (EBR), jasmonic acid (JA), and their signaling inhibitors brassinazole (Brz)/sodium diethyldithiocarbamate (DIECA) on the biosynthesis of aroma substances in 'Ruidu Hongyu' grapevine. According to the results, exogenous BR and JA promoted the accumulation of various aroma substances, including hexenal, 2-hexenal, nerol oxide, vanillin, hotrienol, terpineol, neral, nerol, geraniol, and geranic acid. After EBR and JA treatments, most of the genes responsible for terpene, aldehyde, and alcohol biosynthesis expressed at a higher level than the CK group. Relatively, EBR treatment could not only promote endogenous BR biosynthesis and metabolism but also elevate BR signaling transduction. JA treatment contributed to endogenous JA and MeJA accumulation, as well. Through transcriptome sequencing, a total of 3043, 903, 1470, and 607 DEGs were identified in JA vs. JD, JA vs. CK, BR vs. CK, and BR vs. Brz, respectively. There were more DEGs under both EBR and JA treatments at late fruit ripening stages. The findings of this study increase our understanding regarding aroma substances biosynthesis and endogenous BR/JA metabolism in response to exogenous EBR and JA signals.
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Focused ultrasound featuring non-destructive and high sensitivity has attracted widespread attention in biomedical and industrial evaluation. However, most traditional focusing techniques focus on the design and improvement of single-point focusing, neglecting the need to carry more dimensions of multifocal beams. Here we propose an automatic multifocal beamforming method, which is implemented using a four-step phase metasurface. The metasurface composed of four-step phases improves the transmission efficiency of acoustic waves as a matching layer and enhances the focusing efficiency at the target focal position. The change in the number of focused beams does not affect the full width at half maximum (FWHM), revealing the flexibility of the arbitrary multifocal beamforming method. Phase-optimized hybrid lenses reduce the sidelobe amplitude, and excellent agreement is observed between the simulation and experiments for triple-focusing beamforming metasurface lenses. The particle trapping experiment further validates the profile of the triple-focusing beam. The proposed hybrid lens can achieve flexible focusing in three dimensions (3D) and arbitrary multipoint, which may have potential prospects for biomedical imaging, acoustic tweezers, and brain neural modulation.
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Ferroptosis is a type of lipid peroxidation-induced, iron-dependent programmed cell death. Emerging evidence suggests that ferroptosis is intimately connected to tumorigenesis, development, treatment and plays a major role in tumor immune regulation. This study focused on the connection between ferroptosis and immune regulation, which may offer a theoretical basis for targeting ferroptosis and tumor immunotherapy.
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Endotracheal intubation can be associated with certain complications in certain group of patients. However, the relationship between endotracheal intubation and postoperative complications is unclear in patients with pulmonary hypertension (PHTN). This study evaluated the relationship between endotracheal intubation and postoperative complications in non-cardiothoracic and non-obstetric surgery patients with PHTN. A secondhand analysis of non-cardiothoracic, non-obstetric procedures was performed on patients with PHTN between 2007 and 2013 in a hospital at the University of Washington. Multivariable logistic regression analyses were used to calculate the adjusted odds ratios to estimate the association between anesthesia and 30-day postoperative complications. Interaction and stratified analyses were conducted according to the American Society of Anesthesiologists score (ASA), smoking, hypertension, and open surgical approach. A total of 573 patients were included in this study, and the mean age was 60.3; 54% were male. In a multivariate regression model for patients with non-cardiothoracic, non-obstetric surgery combined with PHTN, the risk of 30-day postoperative complications was higher in the tracheal intubation group than in patients with non-intubated anesthesia after adjusting for potential covariates (adjusted odds ratioâ =â 2.47; 95% CI, 1.28-4.78). However, there was no significant difference in postoperative mortality between these groups. Statistical analysis showed no interaction between the variables of tracheal intubation and 30-day postoperative complications. In this study, we found that tracheal intubation anesthesia is associated with increased risk of 30-day postoperative complications in PHTN patients undergoing non-cardiothoracic, non-obstetric surgery. Further studies are needed to confirm our findings.
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Anestesia , Hipertensión Pulmonar , Humanos , Masculino , Persona de Mediana Edad , Femenino , Hipertensión Pulmonar/etiología , Intubación Intratraqueal/efectos adversos , Intubación Intratraqueal/métodos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Periodo Posoperatorio , Anestesia/efectos adversosRESUMEN
Strategies to overcome irreversible cochlear hair cell (HC) damage and loss in mammals are of vital importance to hearing recovery in patients with permanent hearing loss. In mature mammalian cochlea, co-activation of Myc and Notch1 reprograms supporting cells (SC) and promotes HC regeneration. Understanding of the underlying mechanisms may aid the development of a clinically relevant approach to achieve HC regeneration in the nontransgenic mature cochlea. By single-cell RNAseq, we show that MYC/NICD "rejuvenates" the adult mouse cochlea by activating multiple pathways including Wnt and cyclase activator of cyclic AMP (cAMP), whose blockade suppresses HC-like cell regeneration despite Myc/Notch activation. We screened and identified a combination (the cocktail) of drug-like molecules composing of small molecules and small interfering RNAs to activate the pathways of Myc, Notch1, Wnt and cAMP. We show that the cocktail effectively replaces Myc and Notch1 transgenes and reprograms fully mature wild-type (WT) SCs for HC-like cells regeneration in vitro. Finally, we demonstrate the cocktail is capable of reprogramming adult cochlea for HC-like cells regeneration in WT mice with HC loss in vivo. Our study identifies a strategy by a clinically relevant approach to reprogram mature inner ear for HC-like cells regeneration, laying the foundation for hearing restoration by HC regeneration.
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Oído Interno , Células Ciliadas Auditivas , Ratones , Animales , Proliferación Celular/fisiología , Células Ciliadas Auditivas/fisiología , Oído Interno/metabolismo , Cóclea/fisiología , Regeneración/fisiología , MamíferosRESUMEN
Background: Glioblastoma multiforme (GBM) is the most lethal brain cancer in adults, characterized by rapid growth, extensive invasiveness, and poor prognosis, and there is still a lack of effective treatments. Here, we aimed to explore the role of triptolide (TPL), purified from Tripterygium wilfordii Hook F, on glioblastoma cell growth, apoptosis, proliferation, migration and invasion, as well as potential underlying mechanisms. Methods: The publicly available clinical data of Brain Lower Grade Glioma (LGG) from The Cancer Genome Atlas (TCGA) had been screened to observe PROX1 expression. The Kaplan-Meier analysis was used to analyze the relationship between PROX1 expression and GBM prognosis. CCK8, cell cycle, EDU, apoptosis, wound healing, and transwell assays were performed to detect the effects of TPL on glioblastoma U251 cell viability, cell cycle, proliferation, apoptosis, migration and invasion, respectively. Further, a soft agar colony assay was used to calculate the growth of glioblastoma cells. The qRT-PCR and western blot were conducted to quantify PROX1 mRNA and protein levels. The transcriptional regulation of TPL was detected by Dual luciferase reporter assay. Results: We found that TPL inhibited glioblastoma cell viability, proliferation, cell cycle, migration and invasion, but enhanced apoptosis in a dose-dependent manner. The expression of cell cycle inhibitor, P21, and pro-apoptosis factor, Bax was increased, while invasion-related factors MMP2 and MMP9 were silenced after TPL treatments. Mechanistically, TPL showed transcriptional inhibition of PROX1 appearance. Moreover, ectopic expression of PROX1 partially rescued the effects of TPL on glioblastoma cell viability, proliferation, apoptosis, migration and invasion, and on the expression of cell function-related genes. Conclusion: This study verified that TPL inhibited the progression of glioblastoma cells by transcriptionally depressing the expression of PROX1.
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Acoustic microscopes and acoustic tweezers have great value in the application of microparticle manipulation, biomedical research and non-destructive testing. Ultrahigh frequency (UHF) ultrasonic transducers act as the key component in acoustic microscopes, and acoustic tweezers and acoustic lenses are essential parts of UHF ultrasonic transducers. Therefore, the preparation of acoustic lenses is crucial. Silicon is a suitable material for preparing acoustic lenses because of its high acoustic velocity, low acoustic attenuation and excellent machinability. In previous research, silicon lenses were mainly prepared by etching. However, etching has some drawbacks. The etching of large sizes is complex, time-consuming and expensive. Furthermore, vertical etching is preferred to spherical etching. Thus, a new method of ultra-precision machining was introduced to prepare silicon lenses. In this paper, silicon lenses with an aperture of 892 µm and a depth of 252 µm were prepared. Then, UHF ultrasonic transducers with a center frequency of 157 MHz and a -6-dB bandwidth of 52% were successfully prepared based on silicon lenses. The focal distance of the transducers was 736 µm and the F-number was about 0.82. The transducers had a lateral resolution of 11 µm and could distinguish the 13 µm slots on silicon wafers clearly.