Phosphorylation and dephosphorylation are primary means for rapid regulation of a variety of neuronal functions, such as membrane excitability, neurotransmitter release, and gene expression. Voltage-gated Ca2+ channels are targets for phosphorylation by a variety of second messengers through activation of different types of protein kinases (PKs). Protein phosphatases (PPs), like PKs, are equally important in regulating Ca2+ channels in neurons. However, much less is understood about whether and how a particular type of PP contributes to regulating neuronal Ca2+ channel activities. This is primarily because of the lack of specific inhibitors/activators for different types of PPs, particularly the PP2c family. The functional roles of PP2c and its substrates in the brain remain virtually unknown. During our yeast two-hybrid screening, PP2calpha was pulled out by both N- and P/Q-type Ca2+ channel C termini. This raised the possibility that PP2calpha might be associated with voltage-gated Ca2+ channels for regulation of the Ca(2+) channel activity. Biochemical studies show that PP2calpha binds directly to neuronal Ca2+ channels forming a functional protein complex in vivo. PP2calpha, unlike PP1, PP2a and PP2b, is more effective in dephosphorylation of neuronal Ca2+ channels after their phosphorylation by PKC. In hippocampal neurons, disruption of the PP2calpha-Ca2+ channel interaction significantly enhances the response of Ca2+ channels to modulation by PKC. Thus, the PP2calpha-Ca2+ channel complex is responsible for rapid dephosphorylation of Ca2+ channels and may contribute to regulation of synaptic transmission in neurons.
In recent times, disulfidptosis, an intricate form of cellular demise, has garnered attention due to its impact on prognosis, tumor progression and treatment response. Nevertheless, the exact significance of disulfidptosis-related genes (DisRGs) in glioblastoma (GBM) remains enigmatic. The GEO and TCGA databases provided transcriptional and clinically relevant data on tumor samples, while the GTEx database provided data on healthy tissues. Disulfidptosis-related genes (DisRGs) were procured from previous scholarly investigations. The expression profile of DisRGs was initially scrutinized among patients diagnosed with GBM, subsequent to which their prognostic value was explored. Through consensus clustering, we constructed DisRGs-related clusters and gene subtypes. Our results established that the DisRG-related clusters had differentially expressed genes, resulting in a DisulfidptosisScore model, which had a positive prognostic value. The differential expression profile of 24 DisRGs between GBM samples and healthy samples was acquired. Through consensus cluster analysis, two distinct disulfidptosis subtypes, namely DisRGcluster A and DisRGcluster B, were identified. Then, the DisulfidptosisScore model including 4 characteristic genes was constructed.Notably, patients with GBM assigned with lower score demonstrated a considerably longer overall survival (OS) compared to those with higher score. We have effectively devised a prognostic model associated with disulfidptosis, presenting autonomous prognostic predictions for patients with GBM. These findings serve as a valuable addition to the current comprehension of disulfidptosis and offer fresh theoretical substantiation for the development of enhanced treatment strategies.
In the coal mining process, various types of tramp materials will be mixed into the raw coal, which will affect the quality of the coal and endanger the normal operation of the equipment. Automatic detection of tramp materials objects is an important process and basis for efficient coal sorting. However, previous research has focused on the detection of gangue, ignoring the detection of other types of tramp materials, especially small targets. Because the initial Single Shot MultiBox Detector (SSD) lacks the efficient use of feature maps, it is difficult to obtain stable results when detecting tramp materials objects. In this article, an object detection algorithm based on feature fusion and dense convolutional network is proposed, which is called tramp materials in raw coal single-shot detector (TMRC-SSD), to detect five types of tramp materials such as gangue, bolt, stick, iron sheet, and iron chain. In this algorithm, a modified DenseNet is first designed and a four-stage feature extractor is used to down-sample the feature map stably. After that, we use the dilation convolution and multi-branch structure to enrich the receptive field. Finally, in the feature fusion module, we designed cross-layer feature fusion and attention fusion modules to realize the semantic interaction of feature maps. The experiments show that the module we designed is effective. This method is better than the existing model. When the input image is 300 × 300 pixels, it can reach 96.12% MAP and 24FPS. Especially in the detection of small objects, the detection accuracy has increased by 4.1 to 95.57%. The experimental results show that this method can be applied to the actual detection of tramp materials objects in raw coal.
Abstract: Melanoma is one of the deadliest skin cancers and accounts for most skin-related deaths due to strong resistance to chemotherapy drugs. In the present study, we investigated the mechanisms of dabrafenib-induced drug resistance in human melanoma cell lines A375 and MEL624. Our studies support that both endoplasmic reticulum (ER) stress and autophagy were induced in the melanoma cells after the treatment with dabrafenib. In addition, ER stress-induced autophagy protects melanoma cells from the toxicity of dabrafenib. Moreover, inhibition of both ER stress and autophagy promote the sensitivity of melanoma cells to dabrafenib. Taken together, the data suggest that ER stress-induced autophagy determines the sensitivity of melanoma cells to dabrafenib. These results provide us with promising evidence that the inhibition of autophagy and ER stress could serve a therapeutic effect for the conventional dabrafenib chemotherapy. Keywords: melanoma, dabrafenib, ER stress, autophagy, apoptosis
Objective To observe the time-intensity curve characteristics of contrast agents in intraocular tumor.Methods A total of 236 patients (238 eyes) with intraocular tumor were enrolled in this study.All the patients received regular ophthalmologic examination,two dimensional ultrasound,color doppler ultrasonography and contrast-enhanced ultrasonography.There were 166 patients (166 eyes) with choroidal melanoma,16 patients (18 eyes) with choroidal metastatic carcinoma,52 patients (52 eyes) with choroidal hemangioma,two patients (two eyes) with retinal hemangioma.The whole process of contrast-enhanced ultrasound were recorded, and exported as t images of Dicom format.These images were processed by Sonoliver software (Tomteck Company, Germany) to drawn the time-intensity curve of contrast agents in the intraocular tumors.Results All intraocular lesions were completely filled with contrast agent,concentric filling from the periphery to the center can be documented in some cases.The time-intensity curve of choroidal hemangioma and retinal hemangioma were basically the same.The time-intensity curve of choroidal melanoma and choroidal metastatic carcinoma were also basically the same.In the filling phase,all tumors were rapid filling type.In the regression phase,contrast agent subsided earlier than in control tissue within the melanoma or metastatic carcinoma lesions,but subsided synchronous or slightly faster than in control tissue within the choroidal hemangioma and retinal hemangioma lesions.Among 166 eyes with choroidal melanoma,138 eyes (83.1％) were in full compliance with the above changes,28 eyes (16.9％) were largely in line with these changes.All the eyes (100.0％) with choroidal metastatic carcinoma,choroidal hemangioma and retinal hemangioma were in full compliance with the above changes.Conclusion Time-intensity curve is quickly filling and fast regression for malignant intraocular tumors,but is quickly filling and slow regression for benign intraocular tumors.
Key words:
Eye neoplasms/diagnosis; Ultrasonography; Ultrasonography, doppler, color
The powerful five-axis CNC machining capacity of UG NX6.0 was introduced.Five-axis NC machining design process was analyzed.Taking the female die of charger as processing object,its five-axis NC machining technics was designed.Die cavity rough machining,variable-axis finish machinings of surface contour and back gouging were implemented.The 2D simulations were realized.The actual executable five-axis NC machining program was generated through post-processing.The research work provides reference for actual production.
Surface Machining error research in CNC machining technology has been an important research and application of the object.This article analyzed and optimized from the processing methods of analysis and compensation,feed spacing,processing width and tool radius and other aspects,to improve the surface parts processing precision and efficiency,which has a certain practical significance.
Objective
To describe the ultrasonographic features of intraocular lymphoma.
Methods
It was a retrospective analysis of 19 patients (26 eyes) with intraocular lymphoma at the department of ophthalmology, Beijing Tongren Hospital from January 2015 to December 2017. The diagnosis was established by tissue biopsy in 4 patients with diagnostic vitrectomy and 8 with enucleation, and other 7 cases were clinically diagnosed followed by pathological examination of central nervous system lymphoma. The ultrasonographic features of all patients were analyzed.
Results
Of the 19 patients (26 eyes) with intraocular lymphoma, 12 cases (19 eyes) of vitreoretinal lymphoma accounted for 63.2%, of which 7 cases were bilateral eyes, and 7 cases (7 eyes) of uveal lymphoma accounted for 36.8%, all of which were monocular. Ultrasonography of vitreoretinal lymphoma included vitreous opacity, posterior vitreous detachment, partial retinal detachment, irregular hypoechoic lesions under the retina, and CDFI detected blood flow signals in the lesion. There were two different types of ultrasound findings in uveal lymphoma. Five cases (5 eyes) showed diffuse thickening of the uveal membrane with low echo, and irregular hypoechoic mass around the optic nerve and the ball wall, in which CDFI detected abundant blood flow signals. Ultrasound biological microscope examination showed that the iris-ciliary body thickened and the internal echo decreased. This ultrasound finding accounted for 71.4% of uveal lymphoma. Two cases (2 eyes) showed a solitary ciliary-choroid choroidal hypoechoic mass, combined with retinal detachment and blood flow signals with CDFI, accounting for 28.6% of uveal lymphoma.
Conclusions
The ultrasonography of intraocular lymphoma is various. The ultrasound findings of vitreoretinal lymphoma are not specific, while the diffuse thickened uvea and retrobulbar hypoechoic lesions encircled optic nerve and eye wall suggest the possibility of uveal lymphoma.
Key words:
Ultrasonography, Doppler, color; Uvea diseases; Intraocular lymphoma
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)
