MicroRNA-200c overexpression inhibits tumorigenicity and metastasis of CD117+CD44+ ovarian cancer stem cells by regulating epithelial-mesenchymal transition

BACKGROUND: Cancer stem cells (CSCs) are believed to be ‘seed cell’ in cancer recurrence and metastasis. MicroRNAs (miRNAs) can play an important role in the progression of primary tumor towards metastasis by regulating the epithelial-mesenchymal transition (EMT). The goal of this study was to investigate the effect of miRNA-200c overexpression on the EMT, tumorigenicity and metastasis of epithelial ovarian cancer (EOC) CSCs. METHODS: The EOC CD117(+)CD44(+)CSCs were isolated from the human ovarian cancer cell line SKOV3 by using a magnetic-activated cell sorting system, and the lentivirus miR-200c transduced CSCs were then selected for the study. The assays of colony forming, wound healing, cellular migration in vitro and tumor progression in vivo were performed. RESULTS: The miR-200c expression was reduced in the CD117(+)CD44(+)CSCs compared with the non-CD117(+)CD44(+)CSCs. However, the stable overexpression of the miR-200c in the CD117(+)CD44(+)CSCs resulted in a significant down-regulation of ZEB-1 and the Vimentin expression, an upregulation of the E-cadherin expression as well as a decrease of colony forming, migratory and invasion in vitro. Importantly, the miR-200c overexpression significantly inhibited the CD117(+)CD44(+)CSCs xenograft growth and lung metastasis in vivo in nude mice by inhibition of the EMT. In addition, the down-regulation of ZEB-1 showed the same efficacy as the miR-200c overexpression in the CD117(+)CD44(+)CSCs. CONCLUSION: These findings from this study suggest that the miR-200c overexpression may be considered a critical approach for the EOC CD117(+)CD44(+)CSCs in clinical trials

First sodium laser guide star asterism launching platform in China on 1.8m telescope at Gaomeigu Observatory

The application of sodium laser guide star is the key difference between modern adaptive optics system and traditional adaptive optics system. Especially in system like multi-conjugate adaptive optics, sodium laser guide star asterism which is formed by several laser guide stars in certain pattern is required to probe more atmospheric turbulence in different directions. To achieve this, a sodium laser guide star asterism launching platform is required. In this paper, we will introduce the sodium laser guide star asterism launching platform built and tested on the 1.8m telescope of the Gaomeigu Observatory. The platform has two functions: one is to compare the performance of sodium laser guide stars generated by different lasers at the same place; the other is to generate sodium laser guide star asterism with adjustable shape. The field test results at the beginning of 2021 verify the important role of the platform, which is also the first time to realize sodium laser guide star asterism in China

Prevalence of oral frailty in community-dwelling older adults: a systematic review and meta-analysis

BackgroundOlder adults are vulnerable to oral frailty due to factors such as age, education level, physical condition, and limited access to medical resources. Given that oral frailty can lead to adverse outcomes and is often overlooked by policymakers and health professionals, it is important to understand the current state of oral frailty among community-dwelling older adults.DesignSystematic review and meta-analysis.MethodsTwo researchers independently conducted searches in seven databases, extracted data, and assessed the quality of eligible studies. Data from cross-sectional studies or cohort studies with a clear definition of oral frailty. Stata 14.0 was utilized to evaluate the overall prevalence of oral frailty, while Cochrane's Q, I2statistics were employed to assess statistical heterogeneity.ResultsA total of 15 studies were ultimately included in this analysis. The pooled prevalence of oral frailty among community-dwelling older adults was 32% (95% CI: 24%−40%, I2 = 98.9%, P < 0.001). By country, the prevalence was 53% (95% CI: 42%−65%) in China and 22% (95% CI: 19%−39%) in Japan. The incidence of oral frailty was 29% (95% CI: 18%−39%) among those aged 74 and over and 26% (95% CI: 16%−36%) among those under 74. The prevalence of oral frailty was 46% (95% CI: 31%−60%) as assessed by the OFI-8 scale, 18% (95% CI: 14%−22%) using the OF-6 scale, and 37% (95% CI: 34%−39%) with the OFI-5 scale. The rates of oral frailty reported before 2021 and between 2022–2024 were 17% (95% CI: 13%−21%) and 42% (95% CI: 31%−53%), respectively. The rate of oral frailty was 39% (95% CI: 23%−54%) for sample sizes ≤ 500, and 25% (95% CI: 16%−33%) for sample sizes >500. Univariate meta-regression analysis revealed that country, measurement method, and publication year might be sources of heterogeneity. Funnel plot analysis and Egger's test showed no significant publication bias among the eligible studies.ConclusionOur study found that oral frailty affects more than one in three older adults living in the community. This highlights the importance for policymakers and health professionals to screen early and implement effective measures to prevent oral frailty among older adults residing in community settings.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/#searchadvanced, identifier: CRD42024527800

Prevalence and associated factors with oral frailty in middle-aged and older hospitalized patients: a cross-sectional study

BackgroundWith the development of the economy and society, people pay more and more attention to oral health. Oral frailty can limit nutritional intake and make an individual physically weak, which is detrimental to people’s health. Therefore, it is urgent to identify oral frailty and their associated risk factors. In this study, we aimed to evaluate the oral frailty and its influencing factors in Chinese middle-aged and older hospitalized patients.MethodsA cross-sectional study was conducted from May 2023 to February 2024 in 2 tertiary hospitals in Wuhu City, Anhui Province, China. The self-designed sociodemographic information, the Oral Frailty Index-8, the 2-item Connor–Davidson resilience scale (CD-RISC-2), the sarcopenia screening questionnaire, and the three-item short literacy survey were used in this study.ResultsA total of 914 middle-aged and older adults patients were recruited. The prevalence of oral frailty was 48.7% (445/914). In the univariate analysis, oral frailty was significantly associated with age, education, place of residence, monthly income, sarcopenia, resilience, and health literacy. Correlation analysis showed that oral frailty was significantly negatively correlated with sarcopenia, resilience, and health literacy. In the binary logistic regression analysis, oral frailty was significantly associated with sarcopenia, and health literacy. Health literacy was a protective factor of oral frailty.ConclusionThis study aimed to investigate the prevalence of oral frailty and identify the associated influencing factors among middle-aged and older adults patients in Anhui Province, China. This study identified several factors influencing oral frailty in middle-aged and older adults patients. Therefore, the government and relevant departments should implement targeted interventions to improve middle-aged and older adults patients’ oral frailty

Preoperative Alfa-Fetoprotein and Fibrinogen Predict Hepatocellular Carcinoma Recurrence After Liver Transplantation Regardless of the Milan Criteria: Model Development with External Validation

Background/Aims: Patient selection is critically important in improving the outcomes of liver transplantation for hepatocellular carcinoma. The aim of the current study was to identify biochemical measures that could affect patient prognosis after liver transplantation. Methods: A total of 119 patients receiving liver transplantation for hepatocellular carcinoma were used to construct a model for predicting recurrence. The results were validated using an independent sample of 109 patients from independent hospitals. All subjects in both cohorts met the Hangzhou criteria. Results: Analysis of the discovery cohort revealed an association of recurrence with preoperative fibrinogen and AFP levels. A mathematical model was developed for predicting probability of recurrence within 5 years: Y = logit(P) = -4.595 + 0.824 ×fibrinogen concentration (g/L) + 0.641 × AFP score (1 for AFP<=20ng/ml, 2 for 20<AFP<=100ng/ml, 3 for 100<AFP<=200ng/ml, 4 for 200<AFP<=400ng/ml, 5 for AFP> 400ng/ml). At a cutoff score of -0.85, the area under the curve (AUC) was 0.819 in predicting recurrence (vs. 0.655 when using the Milan criteria). In the validation cohort, this model had reasonable performance in predicting 5-year overall survival (68.8% vs. 28.1% in using the -0.85 cutoff, p< 0.001) and disease-free survival (65.7% vs. 25.9%, p< 0.001). The sensitivity and specificity were 77.0% and 62.5%, respectively. The AUC of this newly developed model was similar to that with the Milan criteria (0.698 vs. 0.678). Surprisingly, the DFS in patients with score <= -0.85 under this model but not meeting the Milan criteria was similar to that in patients meeting the Milan criteria (53.8% vs. 60.0%, p=0.380). Conclusions: Preoperative AFP and fibrinogen are useful in predicting recurrence of hepatocellular carcinoma after liver transplantation

Efficient Enrichment of Hepatic Cancer Stem-Like Cells from a Primary Rat HCC Model via a Density Gradient Centrifugation-Centered Method

Background: Because few definitive markers are available for hepatic cancer stem cells (HCSCs), based on physical rather than immunochemical properties, we applied a novel method to enrich HCSCs. Methodology: After hepatic tumor cells (HTCs) were first isolated from diethylinitrosamine-induced F344 rat HCC model using percoll discontinuous gradient centrifugation (PDGC) and purified via differential trypsinization and differential attachment (DTDA), they were separated into four fractions using percoll continuous gradient centrifugation (PCGC) and sequentially designated as fractions I–IV (FI–IV). Morphological characteristics, mRNA and protein levels of stem cell markers, proliferative abilities, induced differentiation, in vitro migratory capacities, in vitro chemo-resistant capacities, and in vivo malignant capacities were determined for the cells of each fraction. Findings: As the density of cells increased, 22.18%, 11.62%, 4.73 % and 61.47 % of primary cultured HTCs were segregated in FI–FIV, respectively. The cells from FIII (density between 1.041 and 1.062 g/ml) displayed a higher nuclear-cytoplasmic ratio and fewer organelles and expressed higher levels of stem cell markers (AFP, EpCAM and CD133) than cells from other fractions (P,0.01). Additionally, in vitro, the cells from FIII showed a greater capacity to self-renew, differentiate into mature HTCs, transit across membranes, close scratches, and carry resistance to chemotherapy than did cells from any other fraction; in vivo, injection of only 1610 4 cells from FIII could generate tumors not only in subcutaneous tissue but also in th

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

JUNO Sensitivity to Invisible Decay Modes of Neutrons

We explore the bound neutrons decay into invisible particles (e.g., $n\rightarrow 3 \nu$ or $nn \rightarrow 2 \nu$) in the JUNO liquid scintillator detector. The invisible decay includes two decay modes: $n \rightarrow { inv}$ and $nn \rightarrow { inv}$. The invisible decays of $s$-shell neutrons in $^{12}{\rm C}$ will leave a highly excited residual nucleus. Subsequently, some de-excitation modes of the excited residual nuclei can produce a time- and space-correlated triple coincidence signal in the JUNO detector. Based on a full Monte Carlo simulation informed with the latest available data, we estimate all backgrounds, including inverse beta decay events of the reactor antineutrino $\bar{\nu}_e$, natural radioactivity, cosmogenic isotopes and neutral current interactions of atmospheric neutrinos. Pulse shape discrimination and multivariate analysis techniques are employed to further suppress backgrounds. With two years of exposure, JUNO is expected to give an order of magnitude improvement compared to the current best limits. After 10 years of data taking, the JUNO expected sensitivities at a 90% confidence level are $\tau/B( n \rightarrow { inv} ) > 5.0 \times 10^{31} \, {\rm yr}$ and $\tau/B( nn \rightarrow { inv} ) > 1.4 \times 10^{32} \, {\rm yr}$.Comment: 28 pages, 7 figures, 4 table

Multi-arm carriers composed of an antioxidant lignin core and poly(glycidyl methacrylate-co-poly(ethylene glycol)methacrylate) derivative arms for highly efficient gene delivery

A lignin-based copolymer with good biocompability was successfully prepared via atom transfer radical polymerization (ATRP) for efficient gene delivery.</p