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Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer. Chemotherapy has been recognized as an optional combination treatment, which enhance the overall survival of OSCC patients. However, the majority of patients would suffer therapeutic resistance, which led to the treatment failure and poor prognosis.
To explore the mechanism of chemoresistance in OSCC, we first constructed two chemoresistant cell lines using Cal27 and HSC4. Then MeRIP sequencing together with bioinformatics analysis and a series of in vitro experiments were used to assess the possible regulation manner of RNA methylation on OSCC chemoresistance. Finally, xenograft models were constructed to confirm the relationship among OSCC chemoresistance.
METTL3/METTL14 upregulation could enhance OSCC chemoresistance. CEBPA-DT overexpression could regulate METTL3/METTL14 expression and further activate downstream BHLHB9. CEBPA-DT overexpression could inhibit the activity of IL-17signaling, resulting in the homeostasis breakdown of immune infiltration and cytokine release. CEBPA-DT overexpression could significantly enhance chemoresistance through METTL3/METTL14/BHLHB9 in vivo, which accelerated the tumor growth.
Our results suggest that CEBPA-DT might regulate OSCC chemoresistance through BHLHB9gene manipulated by METTL3/METTL14 as well as through IL-17signaling inhibition, which may contribute to the assessment of potential therapeutic targets in OSCC chemoresistance.
Our results suggest that CEBPA-DT might regulate OSCC chemoresistance through BHLHB9 gene manipulated by METTL3/METTL14 as well as through IL-17 signaling inhibition, which may contribute to the assessment of potential therapeutic targets in OSCC chemoresistance.
To describe the first wave of hospitalisations of patients testing positive for COVID-19 in South Australia.
Pathology test results for COVID-19 between January and June 2020 were matched against state-wide ED and inpatient data sets.
The impact of the first wave of COVID-19 on South Australian hospitals was 440 unique patients with COVID-19; median ED, hospital and ICU lengths of stay of 4.7h, 9.8 days and 4.1 days, respectively; and a crude mortality rate of 0.23 deaths per 100 000 population (four deaths).
The study sheds light on the characteristics of patients with COVID-19 hospitalised in South Australia.
The study sheds light on the characteristics of patients with COVID-19 hospitalised in South Australia.Extracellular vesicles (EVs) secreted by living cells are expected to deliver biological cargo molecules, including RNA and proteins, to the cytoplasm of recipient cells. There is an increasing need to understand the mechanism of intercellular cargo delivery by EVs. However, the lack of a feasible bioassay has hampered our understanding of the biological processes of EV uptake, membrane fusion, and cargo delivery to recipient cells. Here, we describe a reporter gene assay that can measure the membrane fusion efficiency of EVs during cargo delivery to recipient cells. ALK inhibitor When EVs containing tetracycline transactivator (tTA)-fused tetraspanins are internalized by recipient cells and fuse with cell membranes, the tTA domain is exposed to the cytoplasm and cleaved by tobacco etch virus protease to induce tetracycline responsive element (TRE)-mediated reporter gene expression in recipient cells. This assay (designated as EV-mediated tetraspanin-tTA delivery assay, ETTD assay), enabled us to assess the cytoplasmic cargo delivery efficiency of EVs in recipient cells. With the help of a vesicular stomatitis virus-derived membrane fusion protein, the ETTD assay could detect significant enhancement of cargo delivery efficiency of EVs. Furthermore, the ETTD assay could evaluate the effect of potential cargo delivery enhancers/inhibitors. Thus, the ETTD assay may contribute to a better understanding of the underlying mechanism of the cytoplasmic cargo delivery by EVs."My group has fun by discovering new phenomena … My favorite quote is stay hungry, stay foolish (by Steve Jobs) …" Find out more about Jiawei Zhu in his Introducing … Profile.
Because radiotherapy is indispensible for treating cervical cancer, it is critical to accurately and efficiently delineate the radiation targets. We evaluated a deep learning (DL)-based auto-segmentation algorithm for automatic contouring of clinical target volumes (CTVs) in cervical cancers.
Computed tomography (CT) datasets from 535 cervical cancers treated with definitive or postoperative radiotherapy were collected. A DL tool based on VB-Net was developed to delineate CTVs of the pelvic lymph drainage area (dCTV1) and parametrial area (dCTV2) in the definitive radiotherapy group. The training/validation/test number is 157/20/23. CTV of the pelvic lymph drainage area (pCTV1) was delineated in the postoperative radiotherapy group. The training/validation/test number is 272/30/33. Dice similarity coefficient (DSC), mean surface distance (MSD), and Hausdorff distance (HD) were used to evaluate the contouring accuracy. Contouring times were recorded for efficiency comparison.
The mean DSC, MSD, and HD values for our DL-based tool were 0.88/1.32mm/21.60mm for dCTV1, 0.70/2.42mm/22.44mm for dCTV2, and 0.86/1.15mm/20.78mm for pCTV1. Only minor modifications were needed for 63.5% of auto-segmentations to meet the clinical requirements. The contouring accuracy of the DL-based tool was comparable to that of senior radiation oncologists and was superior to that of junior/intermediate radiation oncologists. Additionally, DL assistance improved the performance of junior radiation oncologists for dCTV2 and pCTV1 contouring (mean DSC increases 0.20 for dCTV2, 0.03 for pCTV1; mean contouring time decrease 9.8min for dCTV2, 28.9min for pCTV1).
DL-based auto-segmentation improves CTV contouring accuracy, reduces contouring time, and improves clinical efficiency for treating cervical cancer.
DL-based auto-segmentation improves CTV contouring accuracy, reduces contouring time, and improves clinical efficiency for treating cervical cancer.Nanoparticle aggregation for constructing functional materials has shown enormous advantages in various applications. Most efforts focused on ordered nanoparticle aggregation for specific functions but were often limited to irreversible aggregation processes due to the thermodynamic equilibrium. Herein, we report a reversible disordered aggregation of SiO2 -PNIPAAm nanoparticles (SPNPs) through thermo-responsive jamming, obtaining smart liquid-solid switchable materials. The smart materials can display a switch between liquid-like state and solid-like state responding to a temperature change. This unique macroscopic behavior originates from the reversible disordered aggregation modulated by temperature-dependent hydrophobic interactions among the SPNPs. Notably, the materials at the solid-like state show anti-impact properties and can withstand the impact of a steel sphere with a speed of 328 cm s-1 . We envision that this finding offers inspiration to design smart liquid-solid switchable materials for impact protection.Fluorescent single crystals that respond to multiple external stimuli are of great interest in molecular machines, sensors, and displays. The integration of photo- or acid-induced fluorescence enhancement and bending in one organic crystal, however, has not been reported yet. Herein, we report the interesting plastic photomechanical bending and switching on of the fluorescence of an azine crystal in a single-crystal transformation, due to extended π-conjugation and molecular slippage. Moreover, the fluorescent plastic bending driven by multiple volatile acid vapors was firstly observed, and attributed to the synergistic effect of push-pull electronic structure and hydrogen bonding. The single crystal also shows high elasticity under external force. In addition, reversible fluorescence switching can be triggered by grinding and solvent fuming, as well as by the adsorption and desorption of HCl vapor. The integration of plastic, elastic bending and switch-on fluorescence into one single crystal provides a new strategy for next-generation smart materials.We performed a retrospective survey and verification of the medical records of death cases of children (and adolescents; aged less then 18 years) between 2014 and 2016 in pediatric specialty training facilities in Japan. Of the 2827 registered cases at 163 facilities, 2348 cases were included. The rate of identified deaths compared with the demographic survey was 18.2%-21.0% by age group. The breakdown of deaths was determined as follows 638 cases (27.2%) were due to external factors or unknown causes, 118 (5.0%) were suspected to involve child maltreatment, 932 (39.7%) were of moderate or high preventability or were indeterminable cases. Further detailed verification was required for 1,333 cases (56.8%). Comparison of the three prefectures with high rates of identified deaths in Japan revealed no significant differences, such as in the distribution of diseases, suggesting that there was little selection bias. The autopsy rate of deaths of unknown cause was 43.4%, indicating a high ratio of forensic autopsieatricians are expected to undertake the identified challenges and promote and lead the implementation of the CDR system.
In this article, we discuss research from the science of teaching and learning and from progressive pedagogy, with the aim of discussing how these fields can help us all become better teachers.
Our methods were based on assessment of the literature and our in-class practices.
We find that the practices of critical progressive pedagogy are rooted in good research practices and are based both on new research and on fundamental aspects of teaching and learning.
While some of the ideas mentioned in this piece might be seen as radical, we argue that everyone can benefit from a discussion of these concepts and ideas. Teaching is something that we all do in various ways. Progressive pedagogy allows us to create classrooms as a space to welcome all learners and also pushes educators toward creating a more diverse, inclusive, and equitable classroom.
While some of the ideas mentioned in this piece might be seen as radical, we argue that everyone can benefit from a discussion of these concepts and ideas. Teaching is something that we all do in various ways. Progressive pedagogy allows us to create classrooms as a space to welcome all learners and also pushes educators toward creating a more diverse, inclusive, and equitable classroom.Neolamarckia cadamba (Roxb.), a close relative of Coffea canephora and Ophiorrhiza pumila, is an important traditional medicine in Southeast Asia. Three major glycosidic monoterpenoid indole alkaloids (MIAs), cadambine and its derivatives 3β-isodihydrocadambine and 3β-dihydrocadambine, accumulate in the bark and leaves, and exhibit antimalarial, antiproliferative, antioxidant, anticancer and anti-inflammatory activities. Here, we report a chromosome-scale N. cadamba genome, with 744.5 Mb assembled into 22 pseudochromosomes with contig N50 and scaffold N50 of 824.14 Kb and 29.20 Mb, respectively. Comparative genomic analysis of N. cadamba with Co. canephora revealed that N. cadamba underwent a relatively recent whole-genome duplication (WGD) event after diverging from Co. canephora, which contributed to the evolution of the MIA biosynthetic pathway. We determined the key intermediates of the cadambine biosynthetic pathway and further showed that NcSTR1 catalyzed the synthesis of strictosidine in N. cadamba. A new component, epoxystrictosidine (C27H34N2O10, m/z 547.
Here's my website: https://www.selleckchem.com/ALK.html
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