1,302 research outputs found

    SadTalker: Learning Realistic 3D Motion Coefficients for Stylized Audio-Driven Single Image Talking Face Animation

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    Generating talking head videos through a face image and a piece of speech audio still contains many challenges. ie, unnatural head movement, distorted expression, and identity modification. We argue that these issues are mainly because of learning from the coupled 2D motion fields. On the other hand, explicitly using 3D information also suffers problems of stiff expression and incoherent video. We present SadTalker, which generates 3D motion coefficients (head pose, expression) of the 3DMM from audio and implicitly modulates a novel 3D-aware face render for talking head generation. To learn the realistic motion coefficients, we explicitly model the connections between audio and different types of motion coefficients individually. Precisely, we present ExpNet to learn the accurate facial expression from audio by distilling both coefficients and 3D-rendered faces. As for the head pose, we design PoseVAE via a conditional VAE to synthesize head motion in different styles. Finally, the generated 3D motion coefficients are mapped to the unsupervised 3D keypoints space of the proposed face render, and synthesize the final video. We conduct extensive experiments to show the superior of our method in terms of motion and video quality.Comment: Project page: https://sadtalker.github.i

    Ghrelin regulates hyperactivity-like behaviors via growth hormone signaling pathway in zebrafish (Danio rerio)

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    IntroductionGhrelin is originally identified as the endogenous ligand for the growth hormone secretagogue receptor (GHSR) and partially acts by stimulating growth hormone (GH) release. Our previous studies have identified GHRELIN as a novel susceptibility gene for human attention-deficit hyperactivity disorder (ADHD), and ghrelin-depleted zebrafish (Danio rerio) display ADHD-like behaviors. However, the underlying molecular mechanism how ghrelin regulates hyperactivity-like behaviors is not yet known.ResultsHere, we performed RNA-sequencing analysis using adult ghrelinΔ/Δ zebrafish brains to investigate the underlying molecular mechanisms. We found that gh1 mRNA and genes related to the gh signaling pathway were significantly reduced at transcriptional expression levels. Quantitative polymerase chain reaction (qPCR) was performed and confirmed the downregulation of gh signaling pathway-related genes in ghrelinΔ/Δ zebrafish larvae and the brain of adult ghrelinΔ/Δ zebrafish. In addition, ghrelinΔ/Δ zebrafish displayed hyperactive and hyperreactive phenotypes, such as an increase in motor activity in swimming test and a hyperreactive phenotype under light/dark cycle stimulation, mimicking human ADHD symptoms. Intraperitoneal injection of recombinant human growth hormone (rhGH) partially rescued the hyperactivity and hyperreactive-like behaviors in ghrelin mutant zebrafish. ConclusionOur results indicated that ghrelin may regulate hyperactivity-like behaviors by mediating gh signaling pathway in zebrafish. And the protective effect of rhGH on ghrelinΔ/Δ zebrafish hyperactivity behavior provides new therapeutic clues for ADHD patients

    Banna Virus, China, 1987–2007

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    Banna viruses (BAVs) have been isolated from pigs, cattle, ticks, mosquitoes, and human encephalitis patients. We isolated and analyzed 20 BAVs newly isolated in China; this finding extends the distribution of BAVs from tropical zone to north temperate climates and demonstrate regional variations in BAV phylogeny and mosquito species possibly involved in BAV transmission

    Emergence of eravacycline heteroresistance in carbapenem-resistant Acinetobacter baumannii isolates in China

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    Carbapenem-resistant Acinetobacter baumannii (CRAB) is resistant to almost all antibiotics. Eravacycline, a newer treatment option, has the potential to treat CRAB infections, however, the mechanism by which CRAB isolates develop resistance to eravacycline has yet to be clarified. This study sought to investigate the features and mechanisms of eravacycline heteroresistance among CRAB clinical isolates. A total of 287 isolates were collected in China from 2020 to 2022. The minimum inhibitory concentration (MIC) of eravacycline and other clinically available agents against A. baumannii were determined using broth microdilution. The frequency of eravacycline heteroresistance was determined by population analysis profiling (PAP). Mutations and expression levels of resistance genes in heteroresistant isolates were determined by polymerase chain reaction (PCR) and quantitative real-time PCR (qRT-PCR), respectively. Antisense RNA silencing was used to validate the function of eravacycline heteroresistant candidate genes. Twenty-five eravacycline heteroresistant isolates (17.36%) were detected among 144 CRAB isolates with eravacycline MIC values ≤4 mg/L while no eravacycline heteroresistant strains were detected in carbapenem-susceptible A. baumannii (CSAB) isolates. All eravacycline heteroresistant strains contained OXA-23 carbapenemase and the predominant multilocus sequence typing (MLST) was ST208 (72%). Cross-resistance was observed between eravacycline, tigecycline, and levofloxacin in the resistant subpopulations. The addition of efflux pump inhibitors significantly reduced the eravacycline MIC in resistant subpopulations and weakened the formation of eravacycline heteroresistance in CRAB isolates. The expression levels of adeABC and adeRS were significantly higher in resistant subpopulations than in eravacycline heteroresistant parental strains (P < 0.05). An ISAba1 insertion in the adeS gene was identified in 40% (10/25) of the resistant subpopulations. Decreasing the expression of adeABC or adeRS by antisense RNA silencing significantly inhibited eravacycline heteroresistance. In conclusion, this study identified the emergence of eravacycline heteroresistance in CRAB isolates in China, which is associated with high expression of AdeABC and AdeRS

    Quantitative association of cerebral blood flow, relaxation times and proton density in young and middle-aged primary insomnia patients: A prospective study using three-dimensional arterial spin labeling and synthetic magnetic resonance imaging

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    ObjectivesTo quantitatively measure the T1 value, T2 value, proton density (PD) value, and cerebral blood flow (CBF) in young and middle-aged primary insomnia (PI) patients, and analyze the correlations between relaxation times, PD, and CBF to explore potential brain changes.MethodsCranial magnetic resonance (MR) images of 44 PI patients and 30 healthy subjects were prospectively collected for analysis. The T1, T2, PD, and CBF values of the frontal lobe, parietal lobe, temporal lobe, and occipital lobe were independently measured using three-dimensional arterial spin labeling (3D-ASL), synthetic magnetic resonance imaging (syMRI) and a whole-brain automatic segmentation method. The differences of these imaging indices were compared between PI patients and healthy subjects. Follow-up MR images were obtained from PI patients after 6 months to compare with pre-treatment images. The Wilcoxon signed rank test and Spearman rank were used for statistical analysis.ResultsBilateral CBF asymmetry was observed in 38 patients, with significant differences in both the T2 value and CBF between the four lobes of the brain (p < 0.01). However, no significant difference was found in the T1 and PD values between the bilateral lobes. A negative correlation was found between CBF and T2 values in the right four lobes of patients with primary insomnia (PI). During follow-up examinations, five PI patients showed a disappearance of insomnia symptoms and a decrease in CBF in both brain lobes.ConclusionInsomnia symptoms may be associated with high CBF, and most PI patients have higher CBF and lower T2 values in the right cerebral hemispheres. The right hemisphere appears to play a critical role in the pathophysiology of PI. The 3D-ASL and syMRI technologies can provide a quantitative imaging basis for investigating the brain conditions and changes in young and middle-aged PI patients

    Theranostic Quercetin Nanoparticle for Treatment of Hepatic Fibrosis.

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    The progression of hepatic fibrosis can lead to cirrhosis and hepatic failure, but the development of antifibrotic drugs have faced the challenges of poor effectiveness and targeted specificity. Herein, a theranostic strategy was carried to encapsulate a natural medicine (Quercetin, QR) into hepatitis B core (HBc) protein nanocages (NCs) for imaging and targeted treatment of hepatic fibrosis. It was noted that nanoparticles (RGD-HBc/QR) with surface-displayed RGD targeting ligand exhibit a rather high selectivity toward activated HSCs via the binding affinity with integrin αvβ3, and an efficient inhibition of proliferation and activation of hepatic stellate cells (HSCs) in vitro and in vivo. Once encapsulated in quercetin-gadolinium complex and/or labeled with the NIR fluorescent probes (Cy5.5), the resulting nanoparticles (RGD-HBc/QGd) show great potential as NIR fluorescent and magnetic resonance imaging contrast agents for hepatic fibrosis in vivo. Therefore, the multifunctional integrin-targeted nanoparticles could selectively deliver QR to the activated HSCs, and may provide an effective antifibrotic theranostic strategy

    Construction and Application of an Electronic Spatiotemporal Expression Profile and Gene Ontology Analysis Platform Based on the EST Database of the Silkworm, Bombyx mori

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    An Expressed Sequence Tag (EST) is a short sub-sequence of a transcribed cDNA sequence. ESTs represent gene expression and give good clues for gene expression analysis. Based on EST data obtained from NCBI, an EST analysis package was developed (apEST). This tool was programmed for electronic expression, protein annotation and Gene Ontology (GO) category analysis in Bombyx mori (L.) (Lepidoptera: Bombycidae). A total of 245,761 ESTs (as of 01 July 2009) were searched and downloaded in FASTA format, from which information for tissue type, development stage, sex and strain were extracted, classified and summed by running apEST. Then, corresponding distribution profiles were formed after redundant parts had been removed. Gene expression profiles for one tissue of different developmental stages and from one development stage of the different tissues were attained. A housekeeping gene and tissue-and-stage-specific genes were selected by running apEST, contrasting with two other online analysis approaches, microarray-based gene expression profile on SilkDB (BmMDB) and EST profile on NCBI. A spatio-temporal expression profile of catalase run by apEST was then presented as a three-dimensional graph for the intuitive visualization of patterns. A total of 37 query genes confirmed from microarray data and RT—PCR experiments were selected as queries to test apEST. The results had great conformity among three approaches. Nevertheless, there were minor differences between apEST and BmMDB because of the unique items investigated. Therefore, complementary analysis was proposed. Application of apEST also led to the acquisition of corresponding protein annotations for EST datasets and eventually for their functions. The results were presented according to statistical information on protein annotation and Gene Ontology (GO) category. These all verified the reliability of apEST and the operability of this platform. The apEST can also be applied in other species by modifying some parameters and serves as a model for gene expression study for Lepidoptera

    Effective combinatorial immunotherapy for penile squamous cell carcinoma

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    Penile squamous cell carcinoma (PSCC) accounts for over 95% of penile malignancies and causes significant mortality and morbidity in developing countries. Molecular mechanisms and therapies of PSCC are understudied, owing to scarcity of laboratory models. Herein, we describe a genetically engineered mouse model of PSCC, by co-deletion of Smad4 and Apc in the androgen-responsive epithelium of the penis. Mouse PSCC fosters an immunosuppressive microenvironment with myeloid-derived suppressor cells (MDSCs) as a dominant population. Preclinical trials in the model demonstrate synergistic efficacy of immune checkpoint blockade with the MDSC-diminishing drugs cabozantinib or celecoxib. A critical clinical problem of PSCC is chemoresistance to cisplatin, which is induced by Pten deficiency on the backdrop of Smad4/Apc co-deletion. Drug screen studies informed by targeted proteomics identify a few potential therapeutic strategies for PSCC. Our studies have established what we believe to be essential resources for studying PSCC biology and developing therapeutic strategies
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