Objective: This paper focuses on machine learning based voice conversion (VC) techniques for improving the speech intelligibility of surgical patients who have had parts of their articulators ...removed. Because of the removal of parts of the articulator, a patient's speech may be distorted and difficult to understand. To overcome this problem, VC methods can be applied to convert the distorted speech such that it is clear and more intelligible. To design an effective VC method, two key points must be considered: 1) the amount of training data may be limited (because speaking for a long time is usually difficult for postoperative patients); 2) rapid conversion is desirable (for better communication). Methods: We propose a novel joint dictionary learning based non-negative matrix factorization (JD-NMF) algorithm. Compared to conventional VC techniques, JD-NMF can perform VC efficiently and effectively with only a small amount of training data. Results: The experimental results demonstrate that the proposed JD-NMF method not only achieves notably higher short-time objective intelligibility (STOI) scores (a standardized objective intelligibility evaluation metric) than those obtained using the original unconverted speech but is also significantly more efficient and effective than a conventional exemplar-based NMF VC method. Conclusion: The proposed JD-NMF method may outperform the state-of-the-art exemplar-based NMF VC method in terms of STOI scores under the desired scenario. Significance: We confirmed the advantages of the proposed joint training criterion for the NMF-based VC. Moreover, we verified that the proposed JD-NMF can effectively improve the speech intelligibility scores of oral surgery patients.
The major concept of "oxidative stress" is an excess elevated level of reactive oxygen species (ROS) which are generated from vigorous metabolism and consumption of oxygen. The precise harmonization ...of oxidative stresses between mitochondria and other organelles in the cell is absolutely vital to cell survival. Under oxidative stress, ROS produced from mitochondria and are the major mediator for tumorigenesis in different aspects, such as proliferation, migration/invasion, angiogenesis, inflammation, and immunoescape to allow cancer cells to adapt to the rigorous environment. Accordingly, the dynamic balance of oxidative stresses not only orchestrate complex cell signaling events in cancer cells but also affect other components in the tumor microenvironment (TME). Immune cells, such as M2 macrophages, dendritic cells, and T cells are the major components of the immunosuppressive TME from the ROS-induced inflammation. Based on this notion, numerous strategies to mitigate oxidative stresses in tumors have been tested for cancer prevention or therapies; however, these manipulations are devised from different sources and mechanisms without established effectiveness. Herein, we integrate current progress regarding the impact of mitochondrial ROS in the TME, not only in cancer cells but also in immune cells, and discuss the combination of emerging ROS-modulating strategies with immunotherapies to achieve antitumor effects.
Thioridazine (THD) is a common phenothiazine antipsychotic drug reported to suppress growth in several types of cancer cells. We previously showed that THD acts as an antiglioblastoma and anticancer ...stem-like cell agent. However, the signaling pathway underlying autophagy and apoptosis induction remains unclear. THD treatment significantly induced autophagy with upregulated AMPK activity and engendered cell death with increased sub-G1 in glioblastoma multiform (GBM) cell lines. Notably, through whole gene expression screening with THD treatment, frizzled (Fzd) proteins, a family of G-protein-coupled receptors, were found, suggesting the participation of Wnt/β-catenin signaling. After THD treatment, Fzd-1 and GSK3β-S9 phosphorylation (inactivated form) was reduced to promote β-catenin degradation, which attenuated P62 inhibition. The autophagy marker LC3-II markedly increased when P62 was released from β-catenin inhibition. Additionally, the P62-dependent caspase-8 activation that induced P53-independent apoptosis was confirmed by inhibiting T-cell factor/β-catenin and autophagy flux. Moreover, treatment with THD combined with temozolomide (TMZ) engendered increased LC3-II expression and caspase-3 activity, indicating promising drug synergism. In conclusion, THD induces autophagy in GBM cells by not only upregulating AMPK activity, but also enhancing P62-mediated autophagy and apoptosis through Wnt/β-catenin signaling. Therefore, THD is a potential alternative therapeutic agent for drug repositioning in GBM.
During the outbreak of coronavirus disease 2019 (COVID-19), consistent and considerable differences in disease severity and mortality rate of patients treated in Hubei province compared to those in ...other parts of China have been observed. We sought to compare the clinical characteristics and outcomes of patients being treated inside and outside Hubei province, and explore the factors underlying these differences.
Collaborating with the National Health Commission, we established a retrospective cohort to study hospitalised COVID-19 cases in China. Clinical characteristics, the rate of severe events and deaths, and the time to critical illness (invasive ventilation or intensive care unit admission or death) were compared between patients within and outside Hubei. The impact of Wuhan-related exposure (a presumed key factor that drove the severe situation in Hubei, as Wuhan is the epicentre as well the administrative centre of Hubei province) and the duration between symptom onset and admission on prognosis were also determined.
At the data cut-off (31 January 2020), 1590 cases from 575 hospitals in 31 provincial administrative regions were collected (core cohort). The overall rate of severe cases and mortality was 16.0% and 3.2%, respectively. Patients in Hubei (predominantly with Wuhan-related exposure, 597 (92.3%) out of 647) were older (mean age 49.7
44.9 years), had more cases with comorbidity (32.9%
19.7%), higher symptomatic burden, abnormal radiologic manifestations and, especially, a longer waiting time between symptom onset and admission (5.7
4.5 days) compared with patients outside Hubei. Patients in Hubei (severe event rate 23.0%
11.1%, death rate 7.3%
0.3%, HR (95% CI) for critical illness 1.59 (1.05-2.41)) have a poorer prognosis compared with patients outside Hubei after adjusting for age and comorbidity. However, among patients outside Hubei, the duration from symptom onset to hospitalisation (mean 4.4
4.7 days) and prognosis (HR (95%) 0.84 (0.40-1.80)) were similar between patients with or without Wuhan-related exposure. In the overall population, the waiting time, but neither treated in Hubei nor Wuhan-related exposure, remained an independent prognostic factor (HR (95%) 1.05 (1.01-1.08)).
There were more severe cases and poorer outcomes for COVID-19 patients treated in Hubei, which might be attributed to the prolonged duration of symptom onset to hospitalisation in the epicentre. Future studies to determine the reason for delaying hospitalisation are warranted.
Esophageal cancer (EC) is a type of aggressive cancer without clinically relevant molecular subtypes, hindering the development of effective strategies for treatment. To define molecular subtypes of ...EC, we perform mass spectrometry-based proteomic and phosphoproteomics profiling of EC tumors and adjacent non-tumor tissues, revealing a catalog of proteins and phosphosites that are dysregulated in ECs. The EC cohort is stratified into two molecular subtypes-S1 and S2-based on proteomic analysis, with the S2 subtype characterized by the upregulation of spliceosomal and ribosomal proteins, and being more aggressive. Moreover, we identify a subtype signature composed of ELOA and SCAF4, and construct a subtype diagnostic and prognostic model. Potential drugs are predicted for treating patients of S2 subtype, and three candidate drugs are validated to inhibit EC. Taken together, our proteomic analysis define molecular subtypes of EC, thus providing a potential therapeutic outlook for improving disease outcomes in patients with EC.
Abstract
Covalent organic frameworks (COFs) have served as a family of porous crystalline molecules for various promising applications. However, controllable synthesis of COFs with uniform morphology ...is paramount yet still remains quite challenging. Herein, we report self-templated synthesis of uniform and unique hollow spheres based on highly conjugated three-dimensional (3D) COFs with diameters of 500–700 nm. A detailed time-dependent study reveals the continuous transformation from initial nano sphere-like particles into uniform hollow spherical structures with Ostwald ripening mechanism. Particularly, the resulting 3D COF (3D-Sp-COF) is prone to transport ions more efficiently and the lithium-ion transference number (
t
+
) of 3D-Sp-COF reaches 0.7, which even overwhelms most typical PEO-based polymer electrolytes. Inspiringly, the hollow spherical structures show enhanced capacitance performance with a specific capacitance of 251 F g
−1
at 0.5 A g
−1
, which compares favorably with the vast majority of two-dimensional COFs and other porous electrode materials.
Explosive developments in modern society bring huge fire loads. Previous fire detections at early stages are basically enabled by recognizing abnormal high‐temperatures, smoke particles, and flame ...light signals. However, the identification of these characteristic signals is generally accompanied by an open flame or smoke, which makes it difficult to prevent further serious damage. Herein, a latent‐fire‐detecting strategy of trace ammonia (NH3) analysis based on nanohybrid Ti3C2Tx MXene/MoS2 is proposed. Benefiting from nanoscale high‐density Schottky heterojunctions between MoS2 and Ti3C2Tx MXene, ultrafast (3 s @100 ppm), sub‐ppm (200 ppb minimum), and high‐sensitivity (81.7% @100 ppm and 10.2% @200 ppb) detection of NH3 are enabled. An assembled latent‐fire‐detecting olfactory system (LFOS) based on MXene/MoS2 and interdigital electrodes can monitor trace NH3 releases from different materials (wool, leather, foam, and nylon) during thermal decomposition at latent stages. Notably, the LFOS can detect fire threats at least 84 s earlier than commercialized smoke detectors, providing more fire dealing time and an escape period; this offers a promising latent‐fire‐warning approach for eliminating fire treats at an early stage.
Inspired by the significant contributions of micro/nanoscale Schottky heterojunctions to enhancing gas‐sensing performances, here, a new assembled latent‐fire‐detecting olfactory system (LFOS) based on Ti3C2Tx/MoS2 and interdigital electrodes is developed for recognizing trace NH3 volatiles. The LFOS can detect fire threats at least 84 s earlier than commercialized smoke detectors, significantly increasing the fire dealing time and escape period.
Fluorescent carbon dots functionalization Chen, Bin Bin; Liu, Meng Li; Li, Chun Mei ...
Advances in colloid and interface science,
08/2019, Letnik:
270
Journal Article
Recenzirano
Carbon dots (CDs), as a new type of luminescent zero-dimensional carbon nanomaterial, have been applied in a variety of fields. Currently, functionalization of CDs is an extremely useful method for ...effectively tuning their intrinsic structure and surface state. Heteroatom doping and surface modification are two functionalization strategies for improving the photophysical performance and broadening the range of applications for fluorescent CDs. Heteroatom doping in CDs can be used to tune their intrinsic properties, which has received significant research interests because of its simplicity. Surface modification can be applied for varying active sites and the functional groups on the CDs surface, which can endow fluorescent CDs with the unique properties resulting from functional ligand. In this review, we summarize the structural and physicochemical properties of functional CDs. We focused our review on the latest developments in functionalization strategies for CDs and discuss the detailed characteristics of different functionalization methods. Ultimately, we hope to inform researchers on the latest progress in functionalization of CDs and provide perspectives on future developments for functionalization of CDs and their potential applications.
We summarize the physicochemical properties and functionalization strategies of CDs in hoping to give a guiding role for improving the photophysical performance and broadening the range of applications. Display omitted
•The structural and physicochemical properties of CDs have been systematically summarized.•We focused our review on the latest developments in functionalization strategies for CDs.•Furthermore, we discuss the detailed characteristics of different functionalization methods.