Triptolide has been indicated potent anti-cancer effect involving multiple molecular targets and signaling pathways. High-mobility group box 1 (HMGB1) is a highly conserved DNA-binding protein taking ...part in breast cancer development. The therapeutic effect of triptolide on HMGB1 has not been reported. Thus, our study aims to clarify the role of HMGB1 in triptolide-induced anti-growth effect on breast cancer in vitro and in vivo. We demonstrated that triptolide significantly suppressed growth of breast cancer cells by inhibition of cell viability, clonogenic ability. Further studies evidenced that triptolide treatment not only inhibited HMGB1 mRNA expression, but also decreased supernatant level of HMGB1 in vitro. In line with these observations, exogenous recombinant HMGB1 (rHMGB1) promoted cell proliferation of breast cancer, and triptolide reversed the rHMGB1-promoted proliferative effect. As well, triptolide enhanced the anti-proliferative activity of ethyl pyruvate (EP) (HMGB1 inhibitor). Furthermore, downstream correlation factors (Toll-like receptor 4 (TLR4) and phosphorylated-nuclear factor-kappaB (NF-κB) p65) of HMGB1 were significantly decreased in vitro after triptolide treatment. Consistantly, we confirmed that tumor growth was significantly inhibited after triptolide treatment in vivo. Meanwhile, immunohistochemical analyses showed that triptolide treatment significantly decreased the level of cytoplasmic HMGB1 and TLR4 expression, whereas the expression of NF-κB p65 was relatively higher in cytoplasm, and conversely lower in nucleus as compared to the control group. Collectively, these results demonstrate that triptolide suppresses the growth of breast cancer cells via reduction of HMGB1 expression in vitro and in vivo, which may provide new insights into the treament of breast cancer.
The latest medical image segmentation methods uses UNet and transformer structures with great success. Multiscale feature fusion is one of the important factors affecting the accuracy of medical ...image segmentation. Existing transformer-based UNet methods do not comprehensively explore multiscale feature fusion, and there is still much room for improvement. In this paper, we propose a novel multiresolution aggregation transformer UNet (MRA-TUNet) based on multiscale input and coordinate attention for medical image segmentation. It realizes multiresolution aggregation from the following two aspects: (1) On the input side, a multiresolution aggregation module is used to fuse the input image information of different resolutions, which enhances the input features of the network. (2) On the output side, an output feature selection module is used to fuse the output information of different scales to better extract coarse-grained information and fine-grained information. We try to introduce a coordinate attention structure for the first time to further improve the segmentation performance. We compare with state-of-the-art medical image segmentation methods on the automated cardiac diagnosis challenge and the 2018 atrial segmentation challenge. Our method achieved average dice score of 0.911 for right ventricle (RV), 0.890 for myocardium (Myo), 0.961 for left ventricle (LV), and 0.923 for left atrium (LA). The experimental results on two datasets show that our method outperforms eight state-of-the-art medical image segmentation methods in dice score, precision, and recall.
Paclitaxel (PTX) is one of the widely used chemotherapy drugs in breast cancer (BC) treatment. Unfortunately, the survival rate of metastatic BC patients remains poor due to PTX resistance. ...Therefore, uncovering the underlying mechanism behind the PTX resistance of BC cells is crucial for BC therapy.
The enrichment of circular RNA ATP binding cassette subfamily B member 10 (circ-ABCB10), let-7a-5p and dual specificity phosphatase 7 (DUSP7) was measured by quantitative real time polymerase chain reaction (qRT-PCR) in PTX-resistant and PTX-sensitive BC tissues and cells. Chemoresistance, apoptosis, invasion and autophagy of BC cells were measured by 3-(4, 5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, transwell invasion assay and Western blot assay, respectively. The binding sites between let-7a-5p and circ-ABCB10 or DUSP7 were predicted by Starbase bioinformatic software, and the combination was confirmed by dual-luciferase reporter assay. The protein expression of DUSP7 was examined by Western blot assay. Murine xenograft model was established to confirm the role of circ-ABCB10 in vivo.
Circ-ABCB10 depletion promoted the PTX sensitivity and apoptosis while suppressed the invasion and autophagy of PTX-resistant BC cells. Circ-ABCB10 could bind to let-7a-5p in BC cells, and circ-ABCB10 contributed to PTX resistance of BC cells via let-7a-5p. DUSP7 is a direct target of let-7a-5p in BC cells, and the accumulation of DUSP7 reversed the promoting effects of let-7a-5p overexpression on the PTX sensitivity and apoptosis and the inhibitory impact on the invasion and autophagy of PTX-resistant BC cells. Circ-ABCB10 interference suppressed the growth of BC tumors in vivo.
Circ-ABCB10 mediated PTX resistance, apoptosis, invasion and autophagy of BC cells via let-7a-5p/DUSP7 axis.
This article proposes a unified power flow controller with energy (E-UPFC) installed at the renewable energy grid connection node of the transmission network. Compared with other unified power flow ...controllers (UPFCs), the proposed E-UPFC can not only regulate the power flow on its connected transmission lines, but also suppress the power fluctuations of grid-connected nodes injected with large-scale renewable energy. At the same time, with the installation position of E-UPFC transferred from the transmission line to the node, the original stiff node can be transformed into a flexible node that can regulate the injected power flexibly. First, the PV grid-connected system with E-UPFC is introduced, and its principle of power flow regulation is detailed. In addition, the topology, mathematical modeling, and control strategies of E-UPFC are discussed. Finally, the E-UPFC is applied to the IEEE 3-generator 9-bus system with large-scale renewable energy integration in Matlab/Simulink in order to verify the correctness and feasibility of E-UPFC and its control strategies.
In the sensory epithelium, macrophages have been identified on the scala tympani side of the basilar membrane. These basilar membrane macrophages are the spatially closest immune cells to sensory ...cells and are able to directly respond to and influence sensory cell pathogenesis. While basilar membrane macrophages have been studied in acute cochlear stresses, their behavior in response to chronic sensory cell degeneration is largely unknown. Here we report a systematic observation of the variance in phenotypes, the changes in morphology and distribution of basilar membrane tissue macrophages in different age groups of C57BL/6J mice, a mouse model of age-related sensory cell degeneration. This study reveals that mature, fully differentiated tissue macrophages, not recently infiltrated monocytes, are the major macrophage population for immune responses to chronic sensory cell death. These macrophages display dynamic changes in their numbers and morphologies as age increases, and the changes are related to the phases of sensory cell degeneration. Notably, macrophage activation precedes sensory cell pathogenesis, and strong macrophage activity is maintained until sensory cell degradation is complete. Collectively, these findings suggest that mature tissue macrophages on the basilar membrane are a dynamic group of cells that are capable of vigorous adaptation to changes in the local sensory epithelium environment influenced by sensory cell status.
•Chronic cochlear degeneration activates basilar membrane macrophages.•The activation pattern is affected by the phases of hair cell pathogenesis.•Macrophage activation precedes sensory cell pathogenesis.•Apical versus basal macrophages exhibit different immune response patterns.•Mature tissue macrophages are an immune sensor for chronic hair cell degeneration.
Chinese tree shrew, an animal exhibited closer evolutionary relationship with humans compared to rodents, is getting increasingly attentions as an appealing experimental animal model for human ...diseases. However, a high-efficiency and stable method to establish tree shrew breast precancerous lesions model has not been clearly elucidated. Thus, the current study aimed to explore the way of establishing breast precancerous model in tree shrew and investigate the pathologic characteristics of induced breast precancerous lesions. The results indicated that 7,12-dimethylbenz(a)anthracene (DMBA) could induce breast lesions in tree shrews. However, comparing to DMBA alone, an addition of medroxyprogesterone acetate (MPA) to DMBA critically increased the rate of induced breast lesion in tree shrews. Half of induced breast lesions were intraductal papilloma and the others were atypical ductal hyperplasia. Induced lesions showed positive expression of estrogen receptor α (ERα), progesterone receptor (PR) and cytokeratin 5/6 (CK5/6), but negative expression of human epidermal growth factor receptor-2 (Her-2). The expression of B cell lymphoma-extra large (Bcl-xl) was significantly higher and the expression of B cell lymphoma 2 associated X protein (Bax) was significantly lower in the precancerous lesions (atypical ductal hyperplasia) compared to benign tumor (intraductal papilloma). These results suggest that DMBA is able to induce breast lesions in tree shrews. Combination of DMBA and MPA may be more effective to establish breast precancerous lesion tree shrew models. Tree shrew might be a promising animal model for studying the tumorogenesis of breast cancer.
Attention modulates numerous stages of audiovisual integration, and studies have shown that audiovisual integration is higher in attended conditions than in unattended conditions. However, ...attentional resources are limited for each person, and it is not yet clear how audiovisual integration changes under different attentional loads. Here, we explored how auditory attentional load affects audiovisual integration by applying an auditory/visual discrimination task to evaluate audiovisual integration and a rapid serial auditory presentation (RSAP) task to manipulate auditory attentional resources. The results for peak benefit and positive area under the curve of different probability showed that audiovisual integration was highest in the low attentional load condition and lowest in the high attentional load condition (low > no = medium > high). The peak latency and time window revealed that audiovisual integration was delayed as the attentional load increased (no < low < medium < high). Additionally, audiovisual depression was found in the no, medium, and high attentional load conditions but not in the low attentional load condition. These results suggest that mild auditory attentional load increases audiovisual integration, and high auditory attentional load decreases audiovisual integration.
•Efficiencies of attentional networks and their interactions in PD were investigated.•The executive control efficiency was reduced in both PDS and PDnS.•Higher alerting efficiency and lower orienting ...efficiency were found in PDS.•Largely changed attentional network interactions and correlation were found in PDS.
Attention is composed of three distinct attentional networks: alerting, orienting, and executive control. Previous studies have confirmed that Parkinson’s disease (PD) is associated with executive control deficits; however, the interactions among the three attentional networks and the influence of sleep disturbance in PD patients have not been investigated. Herein, the efficiencies for the three attentional networks and their interactions were evaluated using the revised attention network test. The results showed a significantly slower response and lower accuracy in the PD group than in the normal control group and a significantly slower response and lower accuracy in PD patients with sleep disturbance (PDS) than in PD patients without sleep disturbance (PDnS), which indicates a response deficit in PD and worsening in PDS. Additionally, the executive control efficiency was reduced in both PDS and PDnS, and significantly higher alerting efficiency and lower orienting efficiency were found in PDS. Furthermore, largely changed interactions and correlation patterns of attentional networks were found in PDS but not in PDnS. These results suggested that attentional networks were impaired in PD patients, particularly in those affected by sleep disturbances, and that PDS might establish special connections between attentional networks to compensate for cognitive dysfunction.
It has been generally confirmed that zinc finger and BTB domain containing 7A (ZBTB7A) plays an important role in the occurrence and progression of malignant tumours, but the promotion or inhibition ...effect is related to tumour type. The mechanism between ZBTB7A and breast cancer is not well understood, so further research is needed. In this study, we first investigated the expression of ZBTB7A in tissue samples of clinical breast cancer patients, MDA-MB-231, MCF-7 and MCF-10A cells. Second, we overexpressed the ZBTB7A in MCF-7 cells and silenced the ZBTB7A in MDA-MB-231 cells using lentivirus transfection technology, respectively, and verified the effect of ZBTB7A on migration and invasion of breast cancer cell lines through in vitro cell function experiments, such as wound-healing assay, migration and invasion assay, quantitative real time reverse transcriptase (qRT-PCR) and western blot. Then, the correlation between the above influences, epithelial-mesenchymal transition (EMT) and NF-κB was analysed. Finally, in vivo tumour transplantation model in nude mice was established to verified the effect of ZBTB7A on metastasis of breast cancer MDA-MB-231 cells. In conclusion, ZBTB7A is highly expressed in cancer tissue, breast cancer cell line MDA-MB-231 and MCF-7. Meanwhile, the high expression of ZBTB7A may promote cell migration, invasion and tumour metastasis, which may be related to EMT events by regulating NF-κB.
Audio-visual integration (AVI) is higher in attended conditions than in unattended conditions. Here, we explore the AVI effect when the attentional recourse is competed by additional visual ...distractors, and its aging effect using single- and dual-tasks. The results showed the highest AVI effect under single-task-attentional-load condition than under no- and dual-task-attentional-load conditions (all
P
< 0.05) in both older and younger groups, but the AVI effect was weaker and delayed for older adults compared to younger adults for all attentional-load conditions (all
P
< 0.05). The non-phase-locked oscillation for AVI analysis illustrated the highest theta and alpha oscillatory activity for single-task-attentional-load condition than for no- and dual-task-attentional-load conditions, and the AVI oscillatory activity mainly occurred in the Cz, CP1 and Oz of older adults but in the Fz, FC1, and Cz of younger adults. The AVI effect was significantly negatively correlated with FC1 (
r
2
= 0.1468,
P
= 0.05) and Cz (
r
2
= 0.1447,
P
= 0.048) theta activity and with Fz (
r
2
= 0.1557,
P
= 0.043), FC1 (
r
2
= 0.1042,
P
= 0.008), and Cz (
r
2
= 0.0897,
P
= 0.010) alpha activity for older adults but not for younger adults in dual task. These results suggested a reduction in AVI ability for peripheral stimuli and a shift in AVI oscillation from anterior to posterior regions in older adults as an adaptive mechanism.
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