Disulfiram/Copper Activates ER Stress to Promote Immunogenic Cell Death of Oral Squamous Cell Carcinoma.

Disulfiram/copper complex (DSF/Cu) was found to have anti-tumor effects in a range of malignancies, including oral squamous cell carcinoma (OSCC), yet its precise mechanism remains unknown. It has been shown that ER stress enhances immunogenic cell death (ICD) in tumor cells, as it can influence the anti-cancer immune system favorably. In this study, we reported that DSF/Cu exhibited a marked inhibitory effect on the growth of OSCC cells, accompanied by cell apoptosis. OSCC cells treated with DSF/Cu showed the hallmarks of immunogenic cell death (ICD), including surface expression of calreticulin (CRT), heat shock protein 70 (HSP70), high mobility-group box 1 (HMGB-1) and adenosine triphosphate (ATP), thus, eliciting the maturation and activation of dendritic cells. Furthermore, we showed DSF/Cu-induced endoplasmic reticulum (ER) stress in OSCC cells. In vivo, results demonstrate that DSF/Cu inhibits tumor growth locally and alters the intratumoral immune cell infiltration and response. In conclusion, DSF/Cu suppresses OSCC development by inducing ICD and ER stress. DSF/Cu has the potential to be a new anti-tumor immunotherapy concept because of its ability to elicit ICD.

Nrf2/HO-1 Alleviates Disulfiram/Copper-Induced Ferroptosis in Oral Squamous Cell Carcinoma.

Accumulating evidence indicates that the disulfiram/copper complex (DSF/Cu) has been shown to have potent antitumor activity against various cancers. This research evaluated the effects and probable mechanisms of DSF/Cu on oral squamous cell carcinoma (OSCC). In this study, we report the toxicity of the DSF/Cu to OSCC both in vitro and in vivo. Our study showed that DSF/Cu reduced the proliferation and clonogenicity of OSCC cells. DSF/Cu also induced ferroptosis. Importantly, we confirmed that DSF/Cu could increase the free iron pool, enhance lipid peroxidation, and eventually result in ferroptosis cell death. Inhibition of NRF2 or HO-1 enhances the sensitivity of OSCC cells to DSF/Cu-induced ferroptosis. DSF/Cu inhibited the xenograft growth of OSCC cells by suppressing the expression of Nrf2/HO-1. In conclusion, these results provide experimental evidence that Nrf2/HO-1 alleviates DSF/Cu-induced ferroptosis in OSCC. We propose that this therapy could be a novel strategy for treating OSCC.

Valence-arousal classification of emotion evoked by Chinese ancient-style music using 1D-CNN-BiLSTM model on EEG signals for college students.

During the COVID-19 pandemic, young people are using multimedia content more frequently to communicate with each other on Internet platforms. Among them, music, as psychological support for a lonely life in this special period, is a powerful tool for emotional self-regulation and getting rid of loneliness. More and more attention has been paid to the music recommender system based on emotion. In recent years, Chinese music has tended to be considered an independent genre. Chinese ancient-style music is one of the new folk music styles in Chinese music and is becoming more and more popular among young people. The complexity of Chinese-style music brings significant challenges to the quantitative calculation of music. To effectively solve the problem of emotion classification in music information search, emotion is often characterized by valence and arousal. This paper focuses on the valence and arousal classification of Chinese ancient-style music-evoked emotion. It proposes a hybrid one-dimensional convolutional neural network and bidirectional and unidirectional long short-term memory model (1D-CNN-BiLSTM). And a self-acquisition EEG dataset for Chinese college students was designed to classify music-induced emotion by valence-arousal based on EEG. In addition to that, the proposed 1D-CNN-BILSTM model verified the performance of public datasets DEAP and DREAMER, as well as the self-acquisition dataset DESC. The experimental results show that, compared with traditional LSTM and 1D-CNN-LSTM models, the proposed method has the highest accuracy in the valence classification task of music-induced emotion, reaching 94.85%, 98.41%, and 99.27%, respectively. The accuracy of the arousal classification task also gained 93.40%, 98.23%, and 99.20%, respectively. In addition, compared with the positive valence classification results of emotion, this method has obvious advantages in negative valence classification. This study provides a computational classification model for a music recommender system with emotion. It also provides some theoretical support for the brain-computer interactive (BCI) application products of Chinese ancient-style music which is popular among young people.

Static coded aperture in robotic X-ray tomography systems.

Coded aperture X-ray computed tomography is a computational imaging technique capable of reconstructing inner structures of an object from a reduced set of X-ray projection measurements. Coded apertures are placed in front of the X-ray sources from different views and thus significantly reduce the radiation dose. This paper introduces coded aperture X-ray computed tomography for robotic X-ray systems which offer positioning flexibility. While single coded-aperture 3D tomography was recently introduced for standard trajectory CT scanning, it is shown that significant gains in imaging performance can be attained by simple modifications in the CT scanning trajectories enabled by emerging dual robotic CT systems. In particular, the subject is fixed on a plane and the CT system uniformly rotates around the r -axis which is misaligned with the coordinate axes. A single stationary coded aperture is placed on front of the robotic X-ray source above the plane and the corresponding X-ray projections are measured by a two-dimensional detector on the second arm of the robotic system. The compressive measurements with misalignment enable the reconstruction of high-resolution three-dimensional volumetric images from the low-resolution coded projections on the detector at a sub-sampling rate. An efficient algorithm is proposed to generate the rotation matrix with two basic sub-matrices and thus the forward model is formulated. The stationary coded aperture is designed based on the Pearson product-moment correlation coefficient analysis and the direct binary search algorithm is used to obtain the optimized coded aperture. Simulations using simulated datasets show significant gains in reconstruction performance compared to conventional coded aperture CT systems.

Effect of input servitization on carbon mitigation: evidence from China's manufacturing industry.

Manufacturing servitization, a new industrial form that integrates manufacturing and service, promotes not only high-quality economic development but also carbon mitigation. By employing the panel data of 14 manufacturing sectors and 17 service sectors from 1995 to 2009 in China, this study sheds light on the effect of manufacturing input servitization on carbon reduction. Results show that input servitization reduces carbon intensity. In terms of the manufacturing heterogeneity, the carbon abatement effect of input servitization in pollution-intensive sectors is greater than that in non-pollution sectors; with respect to the service heterogeneity, more emphasis shall be placed on transportation and business services among all manufacturing industries to curb carbon emissions. Furthermore, the mechanism analysis demonstrates that input servitization reduces carbon intensity by substituting energy elements, promoting technological innovation, and optimizing structure. These conclusions reveal that increasing the level of input servitization helps to coordinate manufacturing industry's development with carbon abatement commitment in China.

Development and Validation of an Artificial Intelligence-Based Image Classification Method for Pathological Diagnosis in Patients With Extramammary Paget's Disease.

Extramammary Paget's disease (EMPD) is a rare, malignant cutaneous adenocarcinoma with a high recurrence rate after surgical resection. Early diagnosis of EMPD is critical as 15%-40% of cases progress into an invasive form and resulting in a dismal prognosis. However, EMPD can be a diagnostic challenge to pathologists, especially in the grassroots hospital, because of its low incidence and nonspecific clinical presentation. Although AI-enabled computer-aided diagnosis solutions have been extensively used in dermatological pathological image analysis to diagnose common skin cancers such as melanoma and basal cell carcinoma, these techniques have yet been applied to diagnose EMPD. Here, we developed and verified a deep learning method with five different deep convolutional neural networks, named ResNet34, ResNet50, MobileNetV2, GoogLeNet, and VGG16, in Asian EMPD pathological image screening to distinguish between Paget's and normal cells. We further demonstrated that the results of the proposed method are quantitative, fast, and repeatable by a retrospective single-center study. The ResNet34 model achieved the best performance with an accuracy of 95.522% in pathological images collected at a magnification of ×40. We envision this method can potentially empower grassroots pathologists' efficiency and accuracy as well as to ultimately provide better patient care.

Can new energy vehicles subsidy curb the urban air pollution? Empirical evidence from pilot cities in China.

New energy vehicles (NEVs) are considered as the potential measure to address urban air pollution, and the Chinese government has launched a pilot subsidy scheme to improve its market penetration. We explored the environmental effects of subsidy on urban air pollution from the extensive and intensive margins and formulated a detailed panel dataset, covering 286 cities in China over the years 2006-2018. Moreover, the PSM-DID method and the instrumental strategy are used to confirm the robustness and validity of empirical results on the basis of comprehensive analysis of potential endogenous issues. The results indicate that the implementation of NEVs subsidy policy could significantly improve urban air quality in general, and as the subsidies scale increased by 1%, air pollution level will be reduced by about 0.15%. Then, from the perspective of the dynamic effect of subsidy, it not only has remarkable current environmental effect, but also an effective technology route in the long run. Simultaneously, compared with traditional intervention tools, subsidies enhance the diffusion of NEVs, reduce emissions of air pollutants while meeting residents' travel needs, and thus achieve incentive compatibility, which is the micro-foundation of environmental improvement. Nonetheless, we cannot simply believe the assertion that NEVs subsidy has positive environmental benefits to each region, as the non-clean generation of electricity in some areas will offset the potential environmental benefits. Additionally, the accelerated phase-out of NEVs subsidies at this stage may cause negative externalities of economy and environment, resulting the deadweight loss of industrial dividends accumulated in the early period. Based on above findings, governments should implement more flexible stimulus policies consistent with NEVs industry developments, rather than drastically reducing subsidies, while paying close attention to decarbonization of energy production stage.

The spillover effects of China's regional environmental markets to local listed firms: a risk Granger causality approach.

Using the quantile GARCH model estimators to gauge the bidirectional risk magnitude and the Granger causality test in risk distributions to detect the existence of risk spillovers, this paper explores the extreme risk spillovers of China's regional carbon markets to local listed firm's stock returns. From the perspectives of macro region level and micro firm level, the findings are outlined as follows. First, among the top three active carbon trading pilots (Hubei, Guangdong, and Shenzhen), Hubei pilot exhibits significant "low risk and high profit" features. Second, the predominant risk spillover effects to local listed firms are heterogeneous across pilots. Specifically, Hubei pilot is dominated by "up-to-down" effect, and Guangdong pilot is dominated by "down-to-down" effect, while Shenzhen pilot has no predominant effect. The heterogeneous risk spillover performance may be caused by the regional divergence in economic development, industry structure, and cap setting concerning each pilot. Third, the risk transmission performance from carbon allowance price to local listed firm's stock returns depends on the firm's belonging sector. That is, environment-related firms, either environment-friendly firms or pollution-intensive firms, are more susceptible to carbon markets' risks compared with environment-unrelated firms. This paper supplies novel information on the risk transmission from carbon markets to local economic entities, which proves valuable not only for firms to improve risk aversion ability but also for policy-makers to perfect carbon markets' mechanism.

Rapid identification of COVID-19 severity in CT scans through classification of deep features.

BACKGROUND: Chest CT is used for the assessment of the severity of patients infected with novel coronavirus 2019 (COVID-19). We collected chest CT scans of 202 patients diagnosed with the COVID-19, and try to develop a rapid, accurate and automatic tool for severity screening follow-up therapeutic treatment. METHODS: A total of 729 2D axial plan slices with 246 severe cases and 483 non-severe cases were employed in this study. By taking the advantages of the pre-trained deep neural network, four pre-trained off-the-shelf deep models (Inception-V3, ResNet-50, ResNet-101, DenseNet-201) were exploited to extract the features from these CT scans. These features are then fed to multiple classifiers (linear discriminant, linear SVM, cubic SVM, KNN and Adaboost decision tree) to identify the severe and non-severe COVID-19 cases. Three validation strategies (holdout validation, tenfold cross-validation and leave-one-out) are employed to validate the feasibility of proposed pipelines. RESULTS AND CONCLUSION: The experimental results demonstrate that classification of the features from pre-trained deep models shows the promising application in COVID-19 severity screening, whereas the DenseNet-201 with cubic SVM model achieved the best performance. Specifically, it achieved the highest severity classification accuracy of 95.20% and 95.34% for tenfold cross-validation and leave-one-out, respectively. The established pipeline was able to achieve a rapid and accurate identification of the severity of COVID-19. This may assist the physicians to make more efficient and reliable decisions.

[Effect of auxiliary resistance forms on the resistance and marginal fitness of complete crowns for short molar preparations].

OBJECTIVE: To evaluate the effect of different auxiliary resistance forms on the resistance and marginal fitness of complete crowns for short molar preparations. METHODS: A total of 70 Nissin resin teeth were prepared with 20° total occlusal convergence, 2.5 mm of occlusocervical height, and a shallow finish line on a milling machine. The milled preparations were then randomly assigned to 7 groups of 10. The first group was used as the control group. A total of 30 dies were modified by preparing interproximal grooves with angles of 0°, 6°, and 20° centered on the mesial and distal surfaces of the dies. The rest of the teeth were prepared with occlusal holes in the center of the occlusal surface milled with the same burs to form 0°, 6°, and 20° holes. Cobalt-chromium copings were fabricated for all specimens. The marginal gap of specific points on the axial surface was measured before and after cementation. The resistance of each specimen was evaluated by applying an external force at an angle of 45° to the long axis of the die by using a universal testing machine in a lingual to buccal direction. The maximum force applied before crown dislodgement was measured. Data were analyzed using the SAS 9.2 software. RESULTS: The results showed that the 0° groove, 0° hole, and 6° hole were effective in improving the resistance of the complete crowns (P<0.05). The 0° groove, 6° groove, 0° hole, 6° hole, and 20° hole had significant difference with the control group in terms of marginal discrepancies (P<0.05). CONCLUSION: Auxiliary resistance forms with less degree indicate greater resistance force but worse marginal fitness. In clinical practice, if the resistance of a preparation is enough, the auxiliary resistance forms should be avoided from being used.

A Robust Reweighted L1-Minimization Imaging Algorithm for Passive Millimeter Wave SAIR in Near Field.

The Compressive Sensing (CS) approach has proven to be useful for Synthetic Aperture Interferometric Radiometer (SAIR) imaging because it provides the same high-resolution capability while using part of interferometric observations compared to traditional methods using the entirety. However, it cannot always obtain the sparsest solution and may yield outliers with the non-adaptive random measurement matrix adopted by current CS models. To solve those problems, this paper proposes a robust reweighted L1-minimization imaging algorithm, called RRIA, to reconstruct images accurately by combining the sparsity and prior information of SAIR images in near field. RRIA employs iterative reweighted L1-minimization to enhance the sparsity to reconstruct SAIR images by computing a new weight factor in each iteration according to the previous SAIR images. Prior information estimated by the energy functional of SAIR images is introduced to RRIA as an additional constraint condition to make the algorithm more robust for different complex scenes. Compared to the current basic CS approach, our simulation results indicate that RRIA can achieve better recovery with the same amount of interferometric observations. Experimental results of different scenes demonstrate the validity and robustness of RRIA.

[Analysis of different endodontic sealers and strategies of root canal irrigation on the bond strength of fiber posts].

OBJECTIVE: To evaluate the influence of eugenol-containing and resin-containing endodontic sealers on the bond strength of fiber posts using different strategies of root canal irrigation. METHODS: Forty-eight mandibular premolars were endodontically treated. The specimens were randomly assigned into two groups according to different endodontic sealers. Group A used Endofil (eugenol-containing endodontic sealer), and group B used AH-plus (resin-containing endodontic sealer). After post space preparation, each group was randomly assigned into three subgroups according to the strategies of root canal irrigation (eight premolars in each subgroup). Group Al and B1: 0.9%NaCl irrigation; Group A2 and B2: 17% ethylene diamine tetraacetic acid (EDTA)+5.25%NaClO+0.9%NaCl irrigation; Group A3 and B3: ultrasonic agitation associated with 1 7%EDTA+5.25%NaClO+0.9%NaCl. One week after the cementation of fiber posts using RelyX™ Unicem, a push-out test was performed to measure the bond strength of the posts. The microstructure of the root canal surface was examined under scanning electron microscope (SEM). RESULTS: The bond strengths of the six groups were as follows: Al (7.96±2.23) MPa, A2 (9.95±2.89) MPa, A3 (18.88±3.69) MPa, B1 (11.41±3.71) MPa, B2 (14.00±4.04) MPa, and B3 (19.14±3.27) MPa. Statistical analysis revealed a significant interaction between the different endodontic sealers and the strategies of root canal irrigation (P<0.05). Lower bond strength was found in group Al but not in group BI (P<0.05), and the same result was revealed when comparing group A2 and B2. No significant difference was observed between group A3 and B3 (P>0.05). SEM showed that the root canal in group A3 and B3 achieved the cleanest surface with nearly all dentine tubules opened. CONCLUSION: The eugenol-containing endodontic sealer can impair the bond strength of fiber posts compared with the resin-containing sealer when the root canal is irrigated by 0.9% NaCl or 17%EDTA+5.25%NaClO+0.9%NaC. No difference was observed between the two sealers when using 17%EDTA+5.25% NaCIO+0.9%NaCl combined with ultrasonic irrigation.