Radiotherapy (RT) is a highly effective multimodal nonsurgical treatment that is essential for patients with advanced colorectal cancer (CRC). Nevertheless, cell subpopulations displaying intrinsic ...radioresistance survive after RT. The reactivation of their proliferation and successful colonization at local or distant sites may increase the risk of poor clinical outcomes. Recently, radioresistant cancer cells surviving RT were reported to exhibit a more aggressive phenotype than parental cells, although the underlying mechanisms remain unclear.
By investigating public databases containing CRC patient data, we explored potential radioresistance-associated signaling pathways. Then, their mechanistic roles in radioresistance were investigated through multiple validation steps using patient-derived primary CRC cells, human CRC cell lines, and CRC xenografts.
Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling was activated in radioresistant CRC tissues in correlation with local and distant metastases. JAK2 was preferentially overexpressed in the CRC stem cell subpopulation, which was accompanied by the phosphorylation of STAT proteins, especially STAT3. JAK2/STAT3 signaling played an essential role in promoting tumor initiation and radioresistance by limiting apoptosis and enhancing clonogenic potential. Mechanistically, the direct binding of STAT3 to the cyclin D2 (CCND2) promoter increased CCND2 transcription. CCND2 expression was required for persistent cancer stem cell (CSC) growth via the maintenance of an intact cell cycle and proliferation with low levels of DNA damage accumulation.
Herein, we first identified JAK2/STAT3/CCND2 signaling as a resistance mechanism for the persistent growth of CSCs after RT, suggesting potential biomarkers and regimens for improving outcomes among CRC patients.
In the adult hippocampus, synapses are constantly formed and eliminated
. However, the exact function of synapse elimination in the adult brain, and how it is regulated, are largely unknown. Here we ...show that astrocytic phagocytosis
is important for maintaining proper hippocampal synaptic connectivity and plasticity. By using fluorescent phagocytosis reporters, we find that excitatory and inhibitory synapses are eliminated by glial phagocytosis in the CA1 region of the adult mouse hippocampus. Unexpectedly, we found that astrocytes have a major role in the neuronal activity-dependent elimination of excitatory synapses. Furthermore, mice in which astrocytes lack the phagocytic receptor MEGF10 show a reduction in the elimination of excitatory synapses; as a result, excessive but functionally impaired synapses accumulate. Finally, Megf10-knockout mice show defective long-term synaptic plasticity and impaired formation of hippocampal memories. Together, our data provide strong evidence that astrocytes eliminate unnecessary excitatory synaptic connections in the adult hippocampus through MEGF10, and that this astrocytic function is crucial for maintaining circuit connectivity and thereby supporting cognitive function.
Recent findings demonstrate that cellulose, a highly abundant, versatile, sustainable, and inexpensive material, can be used in the preparation of very stable and flexible electrochemical energy ...storage devices with high energy and power densities by using electrodes with high mass loadings, composed of conducting composites with high surface areas and thin layers of electroactive material, as well as cellulose‐based current collectors and functional separators. Close attention should, however, be paid to the properties of the cellulose (e.g., porosity, pore distribution, pore‐size distribution, and crystallinity). The manufacturing of cellulose‐based electrodes and all‐cellulose devices is also well‐suited for large‐scale production since it can be made using straightforward filtration‐based techniques or paper‐making approaches, as well as utilizing various printing techniques. Herein, the recent development and possibilities associated with the use of cellulose are discussed, regarding the manufacturing of electrochemical energy storage devices comprising electrodes with high energy and power densities and lightweight current collectors and functional separators.
The recent progress of cellulose, as an appealing natural material that can outperform traditional synthetic materials, for use in energy‐storage devices is described. Cellulose can bring benefits in the fabrication and properties of energy‐storage materials and devices, eventually enabling significant improvements in electrochemical performance, mechanical flexibility, cost competitiveness, and form factors, which are difficult to achieve with conventional power source technologies.
The previous outbreaks of SARS-CoV and MERS-CoV have led researchers to study the role of diagnostics in impediment of further spread and transmission. With the recent emergence of the novel ...SARS-CoV-2, the availability of rapid, sensitive, and reliable diagnostic methods is essential for disease control. Hence, we have developed a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for the specific detection of SARS-CoV-2. The primer sets for RT-LAMP assay were designed to target the nucleocapsid gene of the viral RNA, and displayed a detection limit of 10
2
RNA copies close to that of qRT-PCR
.
Notably, the assay has exhibited a rapid detection span of 30 min combined with the colorimetric visualization. This test can detect specifically viral RNAs of the SARS-CoV-2 with no cross-reactivity to related coronaviruses, such as HCoV-229E, HCoV-NL63, HCoV-OC43, and MERS-CoV as well as human infectious influenza viruses (type B, H1N1pdm, H3N2, H5N1, H5N6, H5N8, and H7N9), and other respiratory disease-causing viruses (RSVA, RSVB, ADV, PIV, MPV, and HRV). Furthermore, the developed RT-LAMP assay has been evaluated using specimens collected from COVID-19 patients that exhibited high agreement to the qRT-PCR. Our RT-LAMP assay is simple to perform, less expensive, time-efficient, and can be used in clinical laboratories for preliminary detection of SARS-CoV-2 in suspected patients. In addition to the high sensitivity and specificity, this isothermal amplification conjugated with a single-tube colorimetric detection method may contribute to the public health responses and disease control, especially in the areas with limited laboratory capacities.
Here, an electrode comprising a Zn hexagonal pyramid array (HPA) coated with a functionalized ZnO layer (Zn@ZnO HPA) is prepared using a periodic anodizing technique. The HPA structure markedly ...increases the electroactive surface area of Zn anode, thus decreasing the local current density. Furthermore, the functionalized ZnO coating layer has a gradient thickness that plays an important role in the selective deposition of Zn ions and the mitigation of side reactions at the interface. The electrochemical stability of the Zn@ZnO HPA electrode, which is closely related to the electroactive surface area and charge transfer resistance, is determined by the “split” value, i.e., ratio of current‐off to current‐on time, a parameter of the periodic anodizing process. Compared with the pristine Zn‐based symmetric cell, the Zn@ZnO HPA‐based symmetric cell is safely operated in the investigated experimental range with the 10‐fold improved running life and 25‐fold enhanced current density without Zn dendrite growth. Moreover, the Zn@ZnO HPA/MnO2 battery exhibits outstanding long‐term cyclability (nearly 100%) with greater than 99% Coulombic efficiency after 1000 cycles at a current density of 9 A g−1. This periodic anodizing technique for ultrastable Zn metal anodes is expected to contribute to the development of inherently safe energy storage systems.
A Zn hexagonal pyramid array coated with a functionalized ZnO layer (Zn@ZnO HPA) prepared via a periodic anodizing process acts as a Zn metal electrode for inherently safe Zn ion aqueous batteries. The unique Zn@ZnO HPA anode shows improved stability without dendrite formation owing to the large surface area and guided Zn ion plating.
Exosomes are small membrane vesicles released by a variety of cell types. Exosomes contain genetic materials, such as mRNAs and microRNAs (miRNAs), implying that they may play a pivotal role in ...cell-to-cell communication. Mesenchymal stem cells (MSCs), which potentially differentiate into multiple cell types, can migrate to the tumor sites and have been reported to exert complex effects on tumor progression. To elucidate the role of MSCs within the tumor microenvironment, previous studies have suggested various mechanisms such as immune modulation and secreted factors of MSCs. However, the paracrine effects of MSC-derived exosomes on the tumor microenvironment remain to be explored. The hypothesis of this study was that MSC-derived exosomes might reprogram tumor behavior by transferring their molecular contents. To test this hypothesis, exosomes from MSCs were isolated and characterized. MSC-derived exosomes exhibited different protein and RNA profiles compared with their donor cells and these vesicles could be internalized by breast cancer cells. The results demonstrated that MSC-derived exosomes significantly down-regulated the expression of vascular endothelial growth factor (VEGF) in tumor cells, which lead to inhibition of angiogenesis in vitro and in vivo. Additionally, miR-16, a miRNA known to target VEGF, was enriched in MSC-derived exosomes and it was partially responsible for the anti-angiogenic effect of MSC-derived exosomes. The collective results suggest that MSC-derived exosomes may serve as a significant mediator of cell-to-cell communication within the tumor microenvironment and suppress angiogenesis by transferring anti-angiogenic molecules.
Microtubule‐associated protein (MAP) 2 has been perceived as a static cytoskeletal protein enriched in neuronal dendritic shafts. Emerging evidence indicates dynamic functions for various MAPs in ...activity‐dependent synaptic plasticity. However, it is unclear how MAP2 is associated with synaptic plasticity mechanisms. Here, we demonstrate that specific silencing of high‐molecular‐weight MAP2 in vivo abolished induction of long‐term potentiation (LTP) in the Schaffer collateral pathway of CA1 pyramidal neurons and in vitro blocked LTP‐induced surface delivery of AMPA receptors and spine enlargement. In mature hippocampal neurons, we observed rapid translocation of a subpopulation of MAP2, present in dendritic shafts, to spines following LTP stimulation. Time‐lapse confocal imaging showed that spine translocation of MAP2 was coupled with LTP‐induced spine enlargement. Consistently, immunogold electron microscopy revealed that LTP stimulation of the Schaffer collateral pathway promoted MAP2 labeling in spine heads of CA1 neurons. This translocation depended on NMDA receptor activation and Ras‐MAPK signaling. Furthermore, LTP stimulation led to an increase in surface‐expressed AMPA receptors specifically in the neurons with MAP2 spine translocation. Altogether, this study indicates a novel role for MAP2 in LTP mechanisms and suggests that MAP2 participates in activity‐dependent synaptic plasticity in mature hippocampal networks.
This study aimed to evaluate and compare the accuracy.
A reference model was prepared with three prepared teeth for three types of restorations: single crown, 3-unit bridge, and inlay. Stone models ...were fabricated from conventional impressions. Digital impressions of the reference model were created using an intraoral scanner (digital models). Physical models were fabricated using a three-dimensional (3D) printer. Reference, stone, and 3D printed models were subsequently scanned using an industrial optical scanner; files were exported in a stereolithography file format. All datasets were superimposed using 3D analysis software to evaluate the accuracy of the complete arch and trueness of the preparations. One-way and two-way analyses of variance (ANOVA) were performed to compare the accuracy among the three model groups and evaluate the trueness among the three types of preparation.
For the complete arch, significant intergroup differences in precision were observed for the three groups (p<.001). However, no significant difference in trueness was found between the stone and digital models (p>.05). 3D printed models had the poorest accuracy.
A two-way ANOVA revealed significant differences in trueness among the model groups (p<.001) and types of preparation (p<.001).
Digital models had smaller root mean square values of trueness of the complete arch and preparations than stone models. However, the accuracy of the complete arch and trueness of the preparations of 3D printed models were inferior to those of the other groups.
Objective:
Alzheimer disease (AD) brains are deficient in brain‐derived neurotrophic factor (BDNF), which regulates synaptic plasticity and memory. MicroRNAs (miRNAs) are ∼22‐nucleotide small ...noncoding RNAs that control a variety of physiological and disease processes. Here, we show that miR‐206 regulates BDNF and memory function in AD mice.
Methods:
Expression of miRNAs was analyzed in Tg2576 AD transgenic mice and human AD brain samples. Regulation of BDNF by a selected miRNA was validated by in silico prediction, target gene luciferase assay, and dendritic spine responses in neurons. AM206, a neutralizing inhibitor of miR‐206 (antagomir), was injected into the third ventricle of Tg2576 mice, after which memory function, synaptogenesis, neurogenesis, and target gene expression were assessed. For noninvasive delivery, antagomirs were administered intranasally.
Results:
The brains of Tg2576 mice and the temporal cortex of human AD brains had increased levels of miR‐206. This miRNA targeted BDNF transcripts, and AM206 prevented the detrimental effects of amyloid‐β42 on BDNF and dendritic spine degeneration in Tg2576 neurons. Injection of AM206 into the cerebral ventricles of AD mice increased the brain levels of BDNF and improved their memory function. In parallel, AM206 enhanced the hippocampal synaptic density and neurogenesis. Furthermore, intranasally administered AM206 also reached the brain and increased BDNF levels and memory function in AD mice.
Interpretation:
Our findings demonstrate a novel miRNA‐dependent regulation of BDNF in AD and suggest possible therapeutic approaches, such as noninvasive intranasal delivery of AM206. ANN NEUROL 2012;72:269–277.
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