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Accurate tissue segmentation of infant brain in magnetic resonance (MR) images is crucial for charting early brain development and identifying biomarkers. Due to ongoing myelination and maturation, in the isointense phase (6-9 months of age), the gray and white matters of infant brain exhibit similar intensity levels in MR images, posing significant challenges for tissue segmentation. Meanwhile, in the adult-like phase around 12 months of age, the MR images show high tissue contrast and can be easily segmented. In this paper, we propose to effectively exploit adult-like phase images to achieve robustmulti-view isointense infant brain segmentation. Specifically, in one way, we transfer adult-like phase images to the isointense view, which have similar tissue contrast as the isointense phase images, and use the transferred images to train an isointense-view segmentation network. On the other way, we transfer isointense phase images to the adult-like view, which have enhanced tissue contrast, for training a segmentation network in the adult-like view. The segmentation networks of different views form a multi-path architecture that performs multi-view learning to further boost the segmentation performance. Since anatomy-preserving style transfer is key to the downstream segmentation task, we develop a Disentangled Cycle-consistent Adversarial Network (DCAN) with strong regularization terms to accurately transfer realistic tissue contrast between isointense and adult-like phase images while still maintaining their structural consistency. Experiments on both NDAR and iSeg-2019 datasets demonstrate a significant superior performance of our method over the state-of-the-art methods.
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Objective: The objective of this study was to investigate the impact of transforming growth factor ß1 (TGF-ß1) on epithelial development using an ex vivo model of submandibular gland (SMG) epithelial-mesenchymal separation. Materials and methods: The ex vivo model was established by separating E13 mouse SMG epithelia and mesenchyme, culturing them independently for 24 h, recombining them, and observing branching morphogenesis. Microarray analysis was performed to evaluate the transcriptome of epithelia treated with and without 1 ng/ml TGF-ß1. Differential gene expression, pathway enrichment, and protein-protein interaction networks were analyzed. Quantitative real-time polymerase chain reaction, Western blot, and immunofluorescence were employed to validate the mRNA and protein levels. Results: Recombined SMGs using separated epithelia and mesenchyme that were cultured for 24 h showed a significant inhibition of epithelial development compared to SMGs recombined immediately after separation. The level of TGF-ß1 decreased in the SMG epithelia after epithelia-mesenchyme separation. Epithelia that were separated from mesenchyme for 24 h and pretreated with 1 ng/ml TGF-ß1 continued to develop after recombination with mesenchyme, while epithelia without 1 ng/ml TGF-ß1 treatment did not. Microarray analysis suggested pathway enrichment related to epithelial development and an upregulation of Sox2 in the 1 ng/ml TGF-ß1-treated epithelia. Further experiments validated the phosphorylation of SMAD2 and SMAD3, upregulation of SOX2 and genes associated with epithelial development, including Prol1, Dcpp1, Bhlha15, Smgc, and Bpifa2. Additionally, 1 ng/ml TGF-ß1 inhibited epithelial apoptosis by improving the BCL2/BAX ratio and reducing cleaved caspase 3. Conclusions: The addition of 1 ng/ml TGF-ß1 maintained the developmental potential of embryonic SMG epithelia separated from mesenchyme for 24 h. This suggests that 1 ng/ml TGF-ß1 may partially compensate for the role of mesenchyme during the separation phase, although its compensation is limited in extent.
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Multi-dimensional diffusion-relaxation correlation (DRC) magnetic resonance imaging (MRI) techniques have recently been developed to investigate tissue microstructures. Sub-voxel tissue heterogeneity is resolved from the local correlation distributions of relaxation time and molecular diffusivity. However, the implementation of these techniques considerably increases the total acquisition time, and simply reducing the scan time may be at the expense of detailed structural resolution. To overcome these limitations, an optimised framework was proposed for acquiring microstructural maps of the human brain on a clinically feasible timescale. First, the acquisition parameters of the multi-dimensional DRC MRI method were sparsely optimised using a genetic algorithm with a fitness function according to the spectral resolution of the correlation map, hardware requirements, and total scan time. Next, the acquired DRC MRI data were processed using a proposed numerical algorithm based on the dynamic inverse Laplace transform (ILT). Prior knowledge from one-dimensional data was then utilised in the iterative procedure to improve the spectral resolution. Finally, the proposed framework was validated using Monte Carlo simulations and experimental data acquired from healthy participants on an MRI scanner. The results demonstrated that the suggested approach is feasible for offering high-resolution DRC maps that correspond to distinct microstructures with a limited amount of optimised acquisition data from two-dimensional DRC sampling space. By significantly reducing scan time while retaining structural resolution, this approach may enable multi-dimensional DRC MRI to be more widely used for quantitative evaluation in biological and medical settings.
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Algoritmos , Encéfalo , Processamento de Imagem Assistida por Computador , Humanos , Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Método de Monte CarloRESUMO
Chemical exchange saturation transfer (CEST) MRI is a molecular imaging tool that provides physiological information about tissues, making it an invaluable tool for disease diagnosis and guided treatment. Its clinical application requires the acquisition of high-resolution images capable of accurately identifying subtle regional changes in vivo, while simultaneously maintaining a high level of spectral resolution. However, the acquisition of such high-resolution images is time consuming, presenting a challenge for practical implementation in clinical settings. Among several techniques that have been explored to reduce the acquisition time in MRI, deep-learning-based super-resolution (DLSR) is a promising approach to address this problem due to its adaptability to any acquisition sequence and hardware. However, its translation to CEST MRI has been hindered by the lack of the large CEST datasets required for network development. Thus, we aim to develop a DLSR method, named DLSR-CEST, to reduce the acquisition time for CEST MRI by reconstructing high-resolution images from fast low-resolution acquisitions. This is achieved by first pretraining the DLSR-CEST on human brain T1w and T2w images to initialize the weights of the network and then training the network on very small human and mouse brain CEST datasets to fine-tune the weights. Using the trained DLSR-CEST network, the reconstructed CEST source images exhibited improved spatial resolution in both peak signal-to-noise ratio and structural similarity index measure metrics at all downsampling factors (2-8). Moreover, amide CEST and relayed nuclear Overhauser effect maps extrapolated from the DLSR-CEST source images exhibited high spatial resolution and low normalized root mean square error, indicating a negligible loss in Z-spectrum information. Therefore, our DLSR-CEST demonstrated a robust reconstruction of high-resolution CEST source images from fast low-resolution acquisitions, thereby improving the spatial resolution and preserving most Z-spectrum information.
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Encéfalo , Aprendizado Profundo , Imageamento por Ressonância Magnética , Imageamento por Ressonância Magnética/métodos , Humanos , Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Animais , Razão Sinal-Ruído , CamundongosRESUMO
Many deep learning based methods have been proposed for brain tumor segmentation. Most studies focus on deep network internal structure to improve the segmentation accuracy, while valuable external information, such as normal brain appearance, is often ignored. Inspired by the fact that radiologists often screen lesion regions with normal appearance as reference in mind, in this paper, we propose a novel deep framework for brain tumor segmentation, where normal brain images are adopted as reference to compare with tumor brain images in a learned feature space. In this way, features at tumor regions, i.e., tumor-related features, can be highlighted and enhanced for accurate tumor segmentation. It is known that routine tumor brain images are multimodal, while normal brain images are often monomodal. This causes the feature comparison a big issue, i.e., multimodal vs. monomodal. To this end, we present a new feature alignment module (FAM) to make the feature distribution of monomodal normal brain images consistent/inconsistent with multimodal tumor brain images at normal/tumor regions, making the feature comparison effective. Both public (BraTS2022) and in-house tumor brain image datasets are used to evaluate our framework. Experimental results demonstrate that for both datasets, our framework can effectively improve the segmentation accuracy and outperforms the state-of-the-art segmentation methods. Codes are available at https://github.com/hb-liu/Normal-Brain-Boost-Tumor-Segmentation.
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Neoplasias Encefálicas , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por ComputadorRESUMO
BACKGROUND: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by abdominal pain, discomfort, and changes in bowel habits. The mechanism underlying IBS remains unclear, and little evidence exists for clarifying the causal relationship between blood metabolites and IBS. METHODS: We conducted a Mendelian randomization (MR) study using two samples. Exposure data for 7824 Europeans were extracted from a genome-wide association study (GWAS) on metabolite levels. The IBS GWAS data from the GWAS database were used for the initial analysis. The primary analysis of causal relationships was conducted using inverse-variance weighting (IVW) with MR-Egger and weighted medians as supplementary analyses. Sensitivity analyses were performed using a combination of the Cochran's Q test, MR-Egger intercept test, Mendelian randomization pleiotropy residual sum and outlier, and leave-one-out analysis. For significant associations, replication and meta-analyses were performed using additional independent IBS case GWAS data released by the FinnGen Consortium R9. To identify the metabolites, score regression, confounding analysis, and reverse MR were performed to further assess the causal relationships between the metabolites. RESULTS: After rigorous screening, we identified four known metabolites to be associated with IBS (stearate, odds ratio [OR]: 0.74, 95% confidence interval [CI]: 0.59-0.92; arginine, OR: 1.36, 95% CI: 1.07-1.74; 1-palmitoylglycerol, OR:1.49, 95% CI: 1.07-2.07; 1-palmitoylglycerophosphoinositol, OR: 0.84, 95% CI: 0.71-0.99). CONCLUSIONS: MR analysis revealed a causal relationship between the four metabolites and IBS, providing preliminary evidence for the pathogenesis of IBS. Our results provide novel insights into the potential biomarkers of IBS.
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Síndrome do Intestino Irritável , Humanos , Síndrome do Intestino Irritável/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Dor Abdominal , CausalidadeRESUMO
Deep learning based multi-atlas segmentation (DL-MA) has achieved the state-of-the-art performance in many medical image segmentation tasks, e.g., brain parcellation. In DL-MA methods, atlas-target correspondence is the key for accurate segmentation. In most existing DL-MA methods, such correspondence is usually established using traditional or deep learning based registration methods at image level with no further feature level adaption. This could cause possible atlas-target feature inconsistency. As a result, the information from atlases often has limited positive and even counteractive impact on the final segmentation results. To tackle this issue, in this paper, we propose a new DL-MA framework, where a novel differentiable atlas feature warping module with a new smooth regularization term is presented to establish feature level atlas-target correspondence. Comparing with the existing DL-MA methods, in our framework, atlas features containing anatomical prior knowledge are more relevant to the target image feature, leading the final segmentation results to a high accuracy level. We evaluate our framework in the context of brain parcellation using two public MR brain image datasets: LPBA40 and NIREP-NA0. The experimental results demonstrate that our framework outperforms both traditional multi-atlas segmentation (MAS) and state-of-the-art DL-MA methods with statistical significance. Further ablation studies confirm the effectiveness of the proposed differentiable atlas feature warping module.
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Aprendizado Profundo , Humanos , Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodosRESUMO
Sucrose esters (SEs) are crucial tobacco smoke flavor precursors and play a significant role in tobacco's functionality. Due to their structural complexity, the separation and analysis of SEs in tobacco remain a major challenge, and massive structures of SEs have not yet been fully identified. In this study, the fractions enriched in SEs were obtained from oriental and flue-cured tobacco through a series of pretreatments, and two types of SEs (Types I and II) were distinguished by liquid chromatography-tandem mass spectrometry (LC-MSn ) analysis, with Type II SEs newly characterized in tobacco. Five groups of main SEs were further purified using preparative high-performance LC (HPLC) coupled to an evaporative light scattering detector, and their structures were characterized by nuclear magnetic resonance spectrometry techniques including 1 H, 13 C, correlation spectroscopy, heteronuclear single quantum correlation, and heteronuclear multiple bond correlation. By combining LC-MSn and nuclear magnetic resonance spectrometry, the structures of eight SE isomers were finally proposed, of which four were newly identified. These findings further enhance the understanding of the structural diversity of SEs in tobacco, serving as a valuable reference for future research on the elucidation, synthesis, and metabolism of SEs.
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Ésteres , Sacarose , Espectrometria de Massas , Cromatografia Líquida , Isomerismo , Cromatografia Líquida de Alta Pressão/métodosRESUMO
BACKGROUND: Anastomosis for gastrointestinal reconstruction has been contentious after low anterior resection of rectal cancer for the past 30 years. Despite the abundance of randomized controlled trials (RCTs) on colon J-pouch (CJP), straight colorectal anastomosis (SCA), transverse coloplast (TCP), and side-to-end anastomosis (SEA), most studies are small and lack reliable clinical evidence. We conducted a systematic review and network meta-analysis to evaluate the effects of the four anastomoses on postoperative complications, bowel function, and quality of life in rectal cancer. METHODS: We assessed the safety and efficacy of CJP, SCA, TCP, and SEA in adult patients with rectal cancer after surgery by searching the Cochrane Library, Embase, and PubMed databases to collect RCTs from the date of establishment to May 20, 2022. Anastomotic leakage and defecation frequency were the main outcome indicators. We pooled data through a random effects model in a Bayesian framework and assessed model inconsistency using the deviance information criterion (DIC) and node-splitting method and inter-study heterogeneity using the I-squared statistics (I2). The interventions were ranked according to the surface under the cumulative ranking curve (SUCRA) to compare each outcome indicator. RESULTS: Of the 474 studies initially evaluated, 29 were eligible RCTs comprising 2631 patients. Among the four anastomoses, the SEA group had the lowest incidence of anastomotic leakage, ranking first (SUCRASEA = 0.982), followed by the CJP group (SUCRACJP = 0.628). The defecation frequency in the SEA group was comparable to those in the CJP and TCP groups at 3, 6, 12, and 24 months postoperatively. In comparison, the defecation frequency in the SCA group 12 months after surgery all ranked fourth. No statistically significant differences were found among the four anastomoses in terms of anastomotic stricture, reoperation, postoperative mortality within 30 days, fecal urgency, incomplete defecation, use of antidiarrheal medication, or quality of life. CONCLUSIONS: This study demonstrated that SEA had the lowest risk of complications, comparable bowel function, and quality of life compared to the CJP and TCP, but further research is required to determine its long-term consequences. Furthermore, we should be aware that SCA is associated with a high defecation frequency.
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Incontinência Fecal , Neoplasias Retais , Adulto , Humanos , Defecação , Fístula Anastomótica , Metanálise em Rede , Neoplasias Retais/cirurgia , Reto/cirurgia , Incontinência Fecal/etiologia , Anastomose Cirúrgica/métodos , Colo/cirurgia , Resultado do TratamentoRESUMO
Time-domain NMR has been extensively utilised to study various characteristics of fluid-saturated porous,materials for instance their mobility, dynamics, stiffness, viscosity and rigidity features, particularly for solid hydrocarbons, rubbers and other polymers. As a unique time-domain technique available for over 30 years, NMR cryoporometry (NMRC) may be used to obtain pore-size distributions of the measured samples. To accurately control the sample temperature, a Peltier thermo-electrically cooled variable temperature probe has been developed and integrated with a highly compact precision NMR time-domain relaxation spectrometer, therefore providing the community with a high-performance instrument for NMR Cryoporometry. To extend the application of aforementioned high-performance NMRC instrument into more senarios, we designed a series of light-weight, compact and integral models with optional NMR frequencies from 12 MHz up to 23 MHz. The measured sample temperature can be precisely controlled from about -60 °C to +80 °C, with an excellent temperature resolution of 10 mK or better near the probe liquid bulk melting point. Therefore, it offers a fairly wide NMRC pore-size distribution ranging from about 1 nm to 2 µm by using water as the probe liquid in the pores, significantly wider than is possible when applying generic NMR Spectrometers for NMRC. A preliminary example of NMR Cryoporometric measurements on two special cement samples is shown in the paper in which the measured pore scales as well as their repeatability are demonstrated. Furthermore, various nano-materials, such as MOF, zeolite and shale kerogen would be potential materials to study by using these new available NMRC instrument models. We aim to offer this technique as a quantitative and easy-to-apply unitary benck-top tool for an even wider range of porous material.
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Imageamento por Ressonância Magnética , Água , Porosidade , Espectroscopia de Ressonância Magnética/métodos , Água/química , TemperaturaRESUMO
Veronica arvensis, which is an annual flowering plant in the plantain family Plantaginaceae, has commonly used as a Chinese herbal medicine to treat malaria in China. Here, the complete plastome of V. arvensis was successfully assembled based on genome skimming sequencing. The plastome of V. arvensis was 149,386 bp in length, comprising a pair of inverted repeats (IR; 24,946 bp) separated by a large single-copy (LSC) region (82,004 bp) and a small single-copy (SSC) region (17,490 bp). The plastid genome encoded 113 unique genes, consisting of 79 protein-coding genes, 30 tRNA genes, and four rRNA genes, with 19 duplicated genes in the IR regions. Six plastid hotspot regions (trnH-psbA, trnK-rps16, atpI-rps2, ndhF-rpl32, ccsA-ndhD and rps15-ycf1) were identified within Veronica. Phylogenetic analysis showed that the representative species from Veronica was monophyletic. V. persica and V. polita formed a maximum clade, followed by sister to V. arvensis.
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Artemisia sphaerocephala Krasch. polysaccharide (ASKP) contained two fractions of 60P and 60S with different molecular weight. It was found the potential performance of interface adsorption and gelation activities for the high molecular weight of 60P in comparison with low molecular weight of 60S. The emulsion stability and droplets filling in gel network was highly dependent on the medium chain triglyceride (MCT) concentrations. The emulsion gels fabricated through a complexation of 60P and gelatin or collagen peptides exhibited significantly improved emulsifying activity and gel strength at higher concentration of MCT. Gelatin or collagen peptide could be adsorbed on the droplets interface and interact with 60P in gel matrix, thus presenting an active filling. However, 60P based emulsion gel complexed with pullulan contributed to a lower strength than hydrogel, which was probably due to the existence of spaces between droplets and gel matrix, weakening the stability of gel network, considered as an inactive filling.
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Artemisia , Artemisia/química , Carboidratos da Dieta , Emulsões , Hidrogéis , Polissacarídeos/químicaRESUMO
BACKGROUND: Amber-like compounds form in tobacco (Nicotiana tabacum) during leaf curing and impact aromatic quality. In particular, cis-abienol, a polycyclic labdane-related diterpenoid, is of research interest as a precursor of these compounds. Glandular trichome cells specifically express copalyl diphosphate synthase (NtCPS2) at high levels in tobacco, which, together with NtABS, are major regulators of cis-abienol biosynthesis in tobacco. RESULTS: To identify the genes involved in the biosynthesis of cis-abienol in tobacco, we constructed transgenic tobacco lines based on an NtCPS2 gene-knockdown model using CRISPR/Cas9 genome-editing technology to inhibit NtCPS2 function in vitro. In mutant plants, cis-abienol and labdene diol contents decreased, whereas the gibberellin and abscisic acid (ABA) contents increased compared with those in wild-type tobacco plants. RNA sequencing analysis revealed the presence of 9514 differentially expressed genes (DEGs; 4279 upregulated, 5235 downregulated) when the leaves of wild-type and NtCPS2-knockdown tobacco plants were screened. Among these DEGs, the genes encoding cis-abienol synthase, ent-kaurene oxidase, auxin/ABA-related proteins, and transcription factors were found to be involved in various biological and physiochemical processes, including diterpenoid biosynthesis, plant hormone signal transduction, and plant-pathogen interactions. CONCLUSIONS: The present study provides insight into the unique transcriptome profile of NtCPS2 knockdown tobacco, allowing for a better understanding of the biosynthesis of cis-abienol in tobacco.
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Nicotiana , Transcriptoma , Sequência de Bases , Regulação da Expressão Gênica de Plantas , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Análise de Sequência de RNA , Nicotiana/genética , Nicotiana/metabolismoRESUMO
BACKGROUND: Serum osteopontin (OPN) concentrations were found to be significantly increased in patients infected with hepatitis B virus (HBV) and patients with hepatocellular carcinoma (HCC). OBJECTIVE: The aim of this study was to determine the association among HCC, OPN, and HBV. METHODS: Two hundred and forty-one subjects were recruited and divided into 6 groups: healthy controls, asymptomatic HBsAg carriers, HBsAg (-) patients with other tumors, HBsAg (+) chronic liver disease patients, HBsAg (+) patients with HCC, and HBsAg (-) patients with HCC or liver cirrhosis (LC). Serum concentrations of OPN and HBsAg were measured and analyzed. RESULTS: OPN concentrations in the HBsAg (+) HCC group were significantly higher than the healthy control group and the HBsAg (-) patients with other cancers (both p = 0.0001). The OPN concentrations of the HBsAg (-) patients with HCC or LC also did not differ significantly from those of the healthy control group (p = 0.075). There is a correlation between the titer of HBsAg and concentrations of OPN in all 3 HBsAg (+) groups (all p values <0.05). CONCLUSIONS: Infection with HBV may increase the serum concentrations of OPN. The association of OPN and HCC may be not attributable to tumor development per se but, rather, to HBV infection.
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Carcinoma Hepatocelular , Hepatite B Crônica , Hepatite B , Neoplasias Hepáticas , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Hepatite B Crônica/complicações , Humanos , OsteopontinaRESUMO
The distal end of parotid duct is often inevitably resected en-block with the buccal mucosa cancer to obtain safety margin and prevent local recurrence. Ligation of duct frequently causes complications like cheek swelling, fistula and gland function loss. The authors describe a novel procedure of combined use of autologous vein graft and vascular coupler to reconstruct the parotid duct defect for buccal mucosa cancer patients who undergo radical neck dissection and free-flap reconstruction, no lumen-stent or cannula is needed. Case examples are shown to illustrate the operative details and different outcomes for two kinds of orifice site choices. Key factors for success include the proper use of Coupler device, right choice of new orifice location and maintenance of lumen patency. For buccal mucosa cancer patients, this novel method for parotid duct reconstruction could effectively reduce postoperative complications and preserve the parotid gland function.
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Mucosa Bucal , Neoplasias Bucais , Bochecha , Humanos , Mucosa Bucal/cirurgia , Neoplasias Bucais/cirurgia , Glândula Parótida , Ductos SalivaresRESUMO
BACKGROUND: LongAn, Guangxi, was the first county in China to implement universal childhood hepatitis B virus (HBV) immunization. We aimed to determine its long-term effects in preventing hepatocellular carcinoma (HCC) 32 years after the immunization programme was launched. METHODS: Information on HCC deaths for LongAn and its neighbouring county, BinYang (where universal hepatitis B vaccination was not started till 2002), were obtained from the national mortality surveillance system. The data were analysed using Poisson regression. RESULTS: The overall age-adjusted mortalities of HCC in LongAn and BinYang during 2017-2018 were 53.3/100,000 and 45.4/100,000, respectively. The mortality of males aged 20-29 years in LongAn, who were vaccinated at birth, was lower (2.7/100,000, 95%CI 0.8-4.5) than that of males in BinYang, who were not vaccinated (4.7/100,000, 95%CI 3.2-6.3). In LongAn, the HCC mortality in adults aged 20-29 years declined significantly from 7.9/100,000 (95%CI 4.4-11.4) in 2004 to 1.4/100,000 (95%CI 0.4-2.4) in 2017-2018 (χ2 = 5.554, p = 0.018). Among those vaccinated at birth, the HCC mortality in mountainous areas, where dietary exposure to aflatoxins is more common, is higher (9.0/100,000, 95%CI 4.5-13.5) than in low-lying areas (6.5/100,000, 95%CI 3.6-9.4) (χ2 = 0.2393, p = 0.618). CONCLUSION: Immunization of infants against HBV has reduced their risk of developing HCC as children and young adults but could not prevent all cases of HCC, suggesting that the major risk factor for HCC in hyperendemic regions is shifting from HBV to other factors. Additional prevention strategies for HCC will be needed in the future.
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Carcinoma Hepatocelular/epidemiologia , Hepatite B/terapia , Neoplasias Hepáticas/epidemiologia , Vacinação/métodos , Adolescente , Adulto , Criança , Pré-Escolar , China , Feminino , Hepatite B/virologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto JovemRESUMO
C6-ceramide is an exogenous short-chain ceramide which can induce apoptosis of multiple cancer cells. Salivary adenoid cystic carcinoma (SACC) is a common salivary gland cancer, which possesses of high rate of local recurrence and distant metastasis. The mechanism of ceramide-induced SACC-83 and SACC-LM cell apoptosis has not been revealed. In our study, gene expression microarray was used to discover that the unfolded protein response (UPR) pathway, especially PRKR-like endoplasmic reticulum kinase (PERK) pathway, was the major activated pathway after treatment of c6-ceramide. D1ER, an endoplasmic-reticulum-targeted Ca2+ indicator, was used to measure Ca2+ release from endoplasmic reticulum (ER) dynamically. We found that inositol 1,4,5-trisphosphate receptor 3 (IP3R3) was activated, leading to Ca2+ release from ER, soon after c6-ceramide treatment. IP3R3 silencing could block UPR, although it could not prevent SACC-83 and SACC-LM cells from apoptosis. Moreover, we found that C/EBP-homologous protein could upregulate in a UPR-independent way. Mitochondria outer membrane permeabilization might play an important role in inducing SACC cell apoptosis.
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Apoptose/efeitos dos fármacos , Carcinoma Adenoide Cístico/metabolismo , Ceramidas/farmacologia , Retículo Endoplasmático/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Neoplasias das Glândulas Salivares/metabolismo , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Animais , Apoptose/genética , Cálcio/metabolismo , Carcinoma Adenoide Cístico/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Ceramidas/administração & dosagem , Citosol/efeitos dos fármacos , Citosol/metabolismo , Retículo Endoplasmático/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Inativação Gênica , Humanos , Receptores de Inositol 1,4,5-Trifosfato/genética , Antígeno Ki-67/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Membranas Mitocondriais/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias das Glândulas Salivares/genética , Transdução de Sinais/genética , Resposta a Proteínas não Dobradas/genética , Ensaios Antitumorais Modelo de Xenoenxerto , eIF-2 Quinase/genética , eIF-2 Quinase/metabolismoRESUMO
Low field two-dimensional nuclear magnetic resonance (2D-NMR) relaxometry is a powerful probe for the characterization of heterogenous, porous media and provides geometrical, physical and chemical information about samples at a molecular level and has been widely used in shale studies. However, NMR signals of shale decay so rapidly, dry sample for particular, that the conventional two-dimensional pulse sequence is either not sensitive enough to short relaxation components or takes too much measurement time. In this paper, 2D-NMR relaxometry correlation based on partial inversion recovery CPMG (PIR-CPMG) pulse sequence is proposed and illustrated to improve the contrast over saturation recovery CPMG (SR-CPMG) and reduces the T1 encoding time of inversion recovery CPMG (IR-CPMG) for petrophysical characterization of shale. Subsequently, the kernel function and inversion method of this sequence are presented and the reliability of the inversion method is testified by numerical simulation. Next, theoretical analysis is conducted to validate the advantages of PIR-CPMG. Ultimately, experiments on copper sulfate solution, artificial sandstone, and shale samples are performed, respectively, to verify the feasibility and effectiveness of the proposed pulse sequence. The results demonstrate that the PIR-CPMG sequence is time-saving and high-contrast, especially for the short relaxation components. This pulse sequence can be utilized in bench-top NMR core analyzer and downhole well logging, potentially, to achieve integrated petrophysical characterization of shale.
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Hepatitis B virus has been classified into 10 genotypes and 48 subgenotypes worldwide. We found previously, through polymerase chain reaction (PCR) amplification of a sample collected in 2011, that an HBsAg carrier was infected with two genotypes (B and D) of HBV. We carried out cloning, sequencing and phylogenetic analysis of the complete genomes and, for confirmation, analysed a sample collected from the same individual in 2018. Fifteen complete sequences were obtained from each sample. The carrier was infected in 2011 by genotypes B and D and by various recombinants, but only genotype D was present in 2018. The major and minor parents of the recombinants are genotypes B and D, respectively, although the recombination breakpoints vary among them. All 23 genotype D isolates form a cluster, branching out from other subgenotype D sequences and supported by a 100â% bootstrap value. Based on complete genome sequences, almost all of the estimated intragroup nucleotide divergence values between our isolates and HBV subgenotypes D1-D10 exceed 4â%. Compared to the other subgenotypes (D1-D10), 35 unique amino acids were present in our isolates. Our data provide evidence for a novel subgenotype, provisionally designated HBV subgenotype D11.