CQNV: A combination of coarsely quantized bitstream and neural vocoder for low rate speech coding

Recently, speech codecs based on neural networks have proven to perform better than traditional methods. However, redundancy in traditional parameter quantization is visible within the codec architecture of combining the traditional codec with the neural vocoder. In this paper, we propose a novel framework named CQNV, which combines the coarsely quantized parameters of a traditional parametric codec to reduce the bitrate with a neural vocoder to improve the quality of the decoded speech. Furthermore, we introduce a parameters processing module into the neural vocoder to enhance the application of the bitstream of traditional speech coding parameters to the neural vocoder, further improving the reconstructed speech's quality. In the experiments, both subjective and objective evaluations demonstrate the effectiveness of the proposed CQNV framework. Specifically, our proposed method can achieve higher quality reconstructed speech at 1.1 kbps than Lyra and Encodec at 3 kbps.Comment: Accepted by INTERSPEECH 202

Inhibition of tumourigenicity of small cell lung cancer cells by suppressing Id3 expression.

Id3 is over-expressed in small cell lung cancer (SCLC). To test whether the tumourigenicity of SCLC cells can be inhibited by suppressing Id3 expression, we transfected siRNA into SCLC cell line GLC-19 and established two sublines (G-Id3-1 and G-Id3-7) which expressed only 30% of the level of Id3 measured in control transfectants. Suppression of Id3 expression in both G-Id3-1 and G-Id3-7 cells produced significant reductions in proliferation rates and in numbers of colonies formed in soft agar assay. When G-Id3-1, G-Id3-7 and the control transfectants were inoculated subcutaneously into 3 groups (8 each) of nude mice, respectively, all (100%) inoculated animals produced tumours. Although there was no difference in tumour incidents amongst the 3 groups, significant reductions were observed in both size and weight of tumours produced by either G-Id3-1 or G-Id3-7 cells. While the final average volume of tumours produced in control group was 1012.1+/-394 mm(3), it was significantly reduced (p2.4-fold higher than that in control. The results in this study suggest that highly expressed Id3 in SCLC cells may be an important therapeutic target for tumour suppression

Modified material constitutive model with activation energy for machining of selective laser melted Ti6Al4V alloys fabricated by different scanning strategies

The thermally activated mechanisms during machining process have a critical influence on the micromechanical properties of metal materials. Thus, a constitutive model describing the response of flow stress on the activated mechanisms has attracted extensive interest. Considering different laser scanning strategies (0°, 67.5° and 90°) and building directions (top and front surfaces), a modified constitutive model with activation energy effect for machining of selective laser melted (SLMed) Ti6Al4V is proposed on the base of Johnson–Cook model. And a new modified term is introduced to describe the dislocation kinetics mechanisms with thermally activated energy with different laser scanning strategies. Besides, the influence of varied modified coefficient on the flow behavior is also studied in the paper, and the modified coefficient produces important effect on the chip morphology and its segmentation. Milling experiments and simulations of SLMed Ti6Al4V with different scanning strategies have been carried out to verify the accuracy of the modified model. Simulation results show that the proposed model can effectively predict serrated chip characteristic and its formation. In addition, the modified model can well simulate the effect of thermally activated energy on the micromechanical evolution during SLMed Ti6Al4V milling process, which is attractive for the dislocation mechanism research of plastic deformation in the cutting operations

Potential Anticancer Mechanisms of a Novel EGFR/DNA-Targeting Combi-Molecule (JDF12) against DU145 Prostate Cancer Cells: An iTRAQ-Based Proteomic Analysis

The development of multitargeting drugs is an emerging trend in cancer research. To promote further development and clinical application of multitargeting drugs, this research was performed. MTT assay and flow cytometry of Annexin V/propidium iodide staining were used to confirm the proapoptotic efficacy of a novel combi-targeting molecule, JDF12, against DU145 prostate cancer (PCa) cells. Differentially expressed proteins between control and JDF12-treated cultures were revealed by isobaric tags for relative and absolute quantitation (iTRAQ), and part of them was confirmed by quantitative PCR. Differentially expressed proteins were further analyzed for function, pathway association, and protein−protein interactions using GO, KEGG, and STRING databases. A total of 119 differentially expressed proteins, 70 upregulated and 49 downregulated, were implicated in the anticancer effects of JDF12. Many of these proteins are involved in biosynthesis, response to stress, energy metabolism, and signal transduction. This study provides important information for understanding the anti-PCa mechanisms of JDF12, and well-designed combi-targeting drugs may possess stronger anticancer efficacy than single-targeting drugs and are thus promising candidates for clinical application

Holocene glacial-marine sedimentation in the Prydz Bay, Antarctica

The typical glacial-marine sedimentation has been recorded from core NP93-2 in the Prydz Bay, Antarctica. The sedimentation processes, sedimentary environment and paleoclimate variations since 12937 a B.P. have been discussed, based on grain size, mineral composition and micropaleontological data, etc.. The climate variation occurred at 10 ka, which expressed that there were increased inputs of terrigenous clastics. The climate change once again but temporarily took place at late Holocene

Safety and Efficacy of First-Line Treatments for Chemotherapy-Naive Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Indirect Comparison

Recently, several drugs have been introduced for the first-line treatment of chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC), but few studies have compared treatment outcomes directly. This indirect comparison among 10 clinical trials (n = 4870 patients) retrieved from PubMed, Web of Science, Cochrane Collaboration, and ClinicalTrails.gov was performed to assess the safety and efficacy of docetaxel, cabazitaxel, abiraterone, enzalutamide, and sipuleucel-T for the initial treatment of mCRPC. No significant differences in primary outcome (overall survival) were found among initial treatments. However, docetaxel had the highest probability (37.53%) of being the most effective, but at the cost of more adverse events, while enzalutamide was associated with the best secondary outcomes (prostate-specific antigen response, progression-free survival, quality of life, and adverse event profile). Thus, docetaxel is recommended as the first agent used for the chemotherapy of mCRPC, while enzalutamide is recommended as the first nonchemotherapy treatment. Additional clinical trials are needed to confirm these findings and establish the optimal order for multidrug treatment of mCRPC

Enzyme-Enhanced Codelivery of Doxorubicin and Bcl-2 Inhibitor by Electrospun Nanofibers for Synergistic Inhibition of Prostate Cancer Recurrence

One of the great challenges of postoperative prostate cancer management is tumor recurrence. Although postoperative chemotherapy presents benefits to inhibit unexpected recurrence, it is still limited due to the drug resistance or intolerable complications of some patients. Electrospun nanofiber, as a promising drug carrier, demonstrating sustained drug release behavior, can be implanted into the tumor resection site during surgery and is conductive to tumor inhibition. Herein, we fabricated electrospun nanofibers loaded with doxorubicin (DOX) and ABT199 to synergistically prevent postoperative tumor recurrence. Enzymatic degradation of the biodegradable electrospun nanofibers facilitated the release of the two drugs. The primarily released DOX from the electrospun nanofibers effectively inhibited tumor recurrence. However, the sustained release of DOX led to drug resistance of the tumor cells, yielding unsatisfactory eradication of the residual tumor. Remarkably, the combined administration of DOX and ABT199, simultaneously released from the nanofibers, not only prolonged the chemotherapy by DOX but also overcame the drug resistance via inhibiting the Bcl-2 activation and thereby enhancing the apoptosis of tumor cells by ABT199. This dual-drug-loaded implant system, combining efficient chemotherapy and anti-drug resistance, offers a prospective strategy for the potent inhibition of postoperative tumor recurrence

Integration analysis of ATAC-seq and RNA-seq provides insight into fatty acid biosynthesis in Schizochytrium limacinum under nitrogen limitation stress

Abstract Background Schizochytrium limacinum holds significant value utilized in the industrial-scale synthesis of natural DHA. Nitrogen-limited treatment can effectively increase the content of fatty acids and DHA, but there is currently no research on chromatin accessibility during the process of transcript regulation. The objective of this research was to delve into the workings of fatty acid production in S. limacinum by examining the accessibility of promoters and profiling gene expressions. Results Results showed that differentially accessible chromatin regions (DARs)-associated genes were enriched in fatty acid metabolism, signal transduction mechanisms, and energy production. By identifying and annotating DARs-associated motifs, the study obtained 54 target transcription factor classes, including BPC, RAMOSA1, SPI1, MYC, and MYB families. Transcriptomics results revealed that several differentially expressed genes (DEGs), including SlFAD2, SlALDH, SlCAS1, SlNSDHL, and SlDGKI, are directly related to the biosynthesis of fatty acids, meanwhile, SlRPS6KA, SlCAMK1, SlMYB3R1, and SlMYB3R5 serve as transcription factors that could potentially influence the regulation of fatty acid production. In the integration analysis of DARs and ATAC-seq, 13 genes were identified, which were shared by both DEGs and DARs-associated genes, including SlCAKM, SlRP2, SlSHOC2, SlTN, SlSGK2, SlHMP, SlOGT, SlclpB, and SlDNAAF3. Conclusions SlCAKM may act as a negative regulator of fatty acid and DHA synthesis, while SlSGK2 may act as a positive regulator, which requires further study in the future. These insights enhance our comprehension of the processes underlying fatty acid and DHA production in S. limacinum. They also supply a foundational theoretical framework and practical assistance for the development of strains rich in fatty acids and DHA

Simulated Fermentation of Strong-Flavor Baijiu through Functional Microbial Combination to Realize the Stable Synthesis of Important Flavor Chemicals

The solid-state fermentation of Baijiu is complicated by the co-fermentation of many microorganisms. The instability of the composition and abundance of the microorganisms in the fermentation process leads to fluctuations of product quality, which is one of the bottleneck problems faced by the Strong-flavor Baijiu industry. In this study, we established a combination of functional microorganisms for the stable fermentation of the main flavor compounds of Baijiu, including medium and long-chain fatty acid ethyl esters such as hexanoic acid, ethyl ester; butanoic acid, ethyl ester; octanoic acid, ethyl ester; acetic acid, ethyl ester; 9,12-octadecadienoic acid, ethyl ester; and decanoic acid, ethyl ester in the fermented grains. Our study investigated the effects of microbial combinations on the fermentation from three aspects: microbial composition, microbial interactions, and microbial association with flavor compounds. The results showed that the added functional microorganisms (Lactobacillus, Clostridium, Caproiciproducens, Saccharomyces, and Aspergillus) became the dominant species in the fermentation system and formed positive interactions with other microorganisms, while the negative interactions between microorganisms were significantly reduced in the fermentation systems that contained both Daqu and functional microorganisms. The redundancy analysis showed that the functional microorganisms (Lactobacillus, Saccharomyces, Clostridium, Cloacibacterium, Chaenothecopsis, Anaerosporobacter, and Sporolactobacillus) showed strong positive correlations with the main flavor compounds (hexanoic acid, ethyl ester; lactic acid, ethyl ester; butanoic acid, ethyl ester; acetic acid, ethyl ester; and octanoic acid, ethyl ester). These results indicated that it was feasible to produce Baijiu with a functional microbial combination, and that this could promote stable Baijiu production