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1.
Front Genet ; 12: 769690, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745232

RESUMO

Brown adipose tissue (BAT) is specialized for energy expenditure, thus a better understanding of the regulators influencing BAT development could provide novel strategies to defense obesity. Many protein-coding genes, miRNAs, and lncRNAs have been investigated in BAT development, however, the expression patterns and functions of circRNA in brown adipogenesis have not been reported yet. This study determined the circRNA expression profiles across brown adipogenesis (proliferation, early differentiated, and fully differentiated stages) by RNA-seq. We identified 3,869 circRNAs and 36.9% of them were novel. We found the biogenesis of circRNA was significantly related to linear mRNA transcription, meanwhile, almost 70% of circRNAs were generated by alternative back-splicing. Next, we examined the cell-specific and differentiation stage-specific expression of circRNAs. Compared to white adipocytes, nearly 30% of them were specifically expressed in brown adipocytes. Further, time-series expression analysis showed circRNAs were dynamically expressed, and 117 differential expression circRNAs (DECs) in brown adipogenesis were identified, with 77 upregulated and 40 downregulated. Experimental validation showed the identified circRNAs could be successfully amplified and the expression levels detected by RNA-seq were reliable. For the potential functions of the circRNAs, GO analysis suggested that the decreased circRNAs were enriched in cell proliferation terms, while the increased circRNAs were enriched in development and thermogenic terms. Bioinformatics predictions showed that DECs contained numerous binding sites of functional miRNAs. More interestingly, most of the circRNAs contained multiple binding sites for the same miRNA, indicating that they may facilitate functions by acting as microRNA sponges. Collectively, we characterized the circRNA expression profiles during brown adipogenesis and provide numerous novel circRNAs candidates for future brown adipogenesis regulating studies.

2.
Mater Horiz ; 8(3): 1029-1036, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34821333

RESUMO

Polymorphic phase transitions are an important route for engineering the properties of two-dimensional materials. Heterostructure construction, on the other hand, not only allows the integration of different functionalities for device applications, but also enables the exploration of new physics arising from proximity coupling. Yet, implementing a design that incorporates the advantages of both remains underexplored. Here, based on comprehensive experimental and theoretical studies of the WSe2/SnSe2 core-shell lateral heterostructure, we demonstrate an unexpected H to T' phase transition in transition metal dichalcogenides (TMDs), correlating with a change of the material properties from a semiconductor to a topological insulator (TI), and propose a novel shell-to-core stress propagation mechanism. This finding offers new insights into TMD phase transitions empowered by the rational design of heterostructures. Owing to the superconducting properties of SnSe2 at low temperatures, the unique TI/superconductor core-shell template is expected to add to the arsenal in the ongoing search for Majorana fermions in condensed matter systems.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34639258

RESUMO

Lead-zinc smelting slag (LZSS) is regarded as a hazardous waste containing heavy metals that poses a significant threat to the environment. LZSS is rich in aluminosilicate, which has the potential to prepare alkali-activated materials and solidify hazardous waste, realizing hazardous waste cotreatment. In this study, the experiment included two parts; i.e., the preparation of alkali-activated LZSS (pure smelting slag) and chromite ore processing residue (COPR) solidification/stabilization. Single-factor and orthogonal experiments were carried out that aimed to explore the effects of various parameters (alkali solid content, water glass modulus, liquid-solid ratio, and initial curing temperature) for alkali-activated LZSS. Additionally, compressive strength and leaching toxicity were the indexes used to evaluate the performance of the solidified bodies containing COPR. As a result, the highest compressive strength of alkali-activated LZSS reached 84.49 MPa, and when 40% COPR was added, the strength decreased to 1.42 MPa. However, the leaching concentrations of Zn and Cr from all the solidified bodies were far below the critical limits (US EPA Method 1311 and China GB5085.3-2007). Heavy-metal ions in LZSS and COPR were immobilized successfully by chemical and physical means, which was detected by analyses including environmental scanning electron microscopy with energy-dispersive spectrometry, Fourier transform infrared spectrometry, and X-ray diffraction.


Assuntos
Álcalis , Metais Pesados , Resíduos Industriais/análise , Chumbo , Metais Pesados/análise , Zinco
4.
Med Phys ; 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34655442

RESUMO

PURPOSE:  On-treatment kV images have been used in tracking patient motion. One challenge of markerless motion tracking in paraspinal SBRT is the reduced contrast when the X-ray beam needs to pass through a large portion of the patient's body, for example, from the lateral direction. Besides, due to the spine's overlapping with the surrounding moving organs in the X-ray images, auto-registration could lead to potential errors. This work aims to automatically extract the spine component from the conventional 2D X-ray images, to achieve more robust and more accurate motion management. METHODS:  A ResNet generative adversarial network (ResNetGAN) consisting of one generator and one discriminator was developed to learn the mapping between 2D kV image and the reference spine digitally reconstructed radiograph (DRR). A tailored multi-channel multi-domain loss function was used to improve the quality of the decomposed spine image. The trained model took a 2D kV image as input and learned to generate the spine component of the X-ray image. The training dataset included 1347 2D kV thoracic and lumbar region X-ray images from 20 randomly selected patients, and the corresponding matched reference spine DRR. Another 226 2D kV images from the remaining four patients were used for evaluation. The resulted decomposed spine images and the original X-ray images were registered to the reference spine DRRs, to compare the spine tracking accuracy. RESULTS:  The decomposed spine image had the mean peak signal-to-noise ratio (PSNR) and structural similarity index measure (SSIM) of 60.08 and 0.99, respectively, indicating the model retained and enhanced the spine structure information in the original 2D X-ray image. The decomposed spine image matching with the reference spine DRR had submillimeter accuracy (in mm) with a mean error of 0.13, 0.12, and a maximum of 0.58, 0.49 in the x - and y -directions (in the imager coordinates), respectively. The accuracy improvement is robust in all lateral and anteroposterior X-ray beam angles. CONCLUSION:  We developed a deep learning-based approach to remove soft tissues in the kV image, leading to more accurate spine tracking in paraspinal SBRT.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34595712

RESUMO

To solve the harm caused by hazardous chromium-containing sludge (CCS, chromium-containing sludge) waste to humans and the environment, this study used attapulgite to strengthen alkali slag to prepare cementitious materials to solidify/stabilize CCS. Single-factor and orthogonal experiments were used to optimize the preparation parameters of alkali slag cementitious materials. The compressive strength, heavy metal leaching toxicity, and microscopic characterization of a CCS solidified body were tested to investigate the solidification effect and mechanism of CCS formation. The best attapulgite content was 4%; the solidified body after the treatment of chromium-containing sludge had a good performance of heavy metal leaching and mechanical properties. The addition of attapulgite enhanced the compressive strength. Compared with the original CCS, the leaching concentration of heavy metals in the solidified body was significantly reduced. Among them, the solidified efficiency of chromium is stable above 90%. The changes in the results of XRD and FTIR for each component were studied. It indicated that the solidified body may solidify/stabilize heavy metals through physical encapsulation of the amorphous form and chemical immobilization. This research recognized the use of waste to treat waste, realized the combined effect of solidification/adsorption, and indicated the possibility of application of attapulgite and its solidified products in construction.

6.
Front Physiol ; 12: 728208, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489740

RESUMO

Obesity and its related metabolic diseases have become great public health threats worldwide. Although accumulated evidence suggests that circRNA is a new type of non-coding RNAs regulating various physiological and pathological processes, little attention has been paid to the expression profiles and functions of circRNAs in white adipose tissue. In this study, 3,771 circRNAs were detected in three stages of white adipogenesis (preadipocyte, differentiating preadipocyte, and mature adipocyte) by RNA-seq. Experimental validation suggested that the RNA-seq results are highly reliable. We found that nearly 10% of genes which expressed linear RNAs in adipocytes could also generate circRNAs. In addition, 40% of them produced multiple circRNA isoforms. We performed correlation analysis and found that a great deal of circRNAs (nearly 50%) and their parental genes were highly correlated in expression levels. A total of 41 differential expression circRNAs (DECs) were detected during adipogenesis and an extremely high ratio of them (80%) were correlated with their parental genes, indicating these circRNAs may potentially play roles in regulating the expression of their parental genes. KEGG enrichment and GO annotation of the parental genes suggesting that the DECs may participate in several adipogenesis-related pathways. Following rigorous selection, we found that many up-regulated circRNAs contain multiple miRNAs binding sites, such as miR17, miR-30c, and miR-130, indicating they may potentially facilitate their regulatory functions by acting as miRNA sponges. These results suggest that plenty of circRNAs are expressed in white adipogenesis and the DECs may serve as new candidates for future adipogenesis regulation.

7.
ACS Omega ; 6(37): 23723-23730, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34568652

RESUMO

Residues from the incineration of hazardous wastes are classified as hazardous byproducts because they contain heavy metals. Chromium-containing sludge (CCS) is industrial sludge produced during the electroplating process and includes heavy metals, such as Cr, Pb, and Cu. These heavy metals can infiltrate natural ecosystems and cause significant environmental damage. To limit the toxicity of leached products, hazardous waste incineration residues (HWIRs) can be repurposed as raw materials for producing glass-ceramics. In this study, we designed an orthogonal experiment to optimize the heat treatment process, yielding glass-ceramics with excellent properties and realizing heavy metal solidification. The toxic characteristic leaching procedure was used to determine the leaching toxicity of the cosintered solidified heavy metals, revealing that their solidification efficiencies exceed 90%. Moreover, X-ray diffraction analysis indicates that certain heavy metals participate in the formation of heavy-metal-containing crystal lattices (FeCr2O4 and PbFe12O19), thereby reducing their leaching concentration. These results show that cosintering HWIR and CCS is an effective approach for heavy metal solidification and provides valuable insights into its utilization for producing building materials.

8.
Front Cell Dev Biol ; 9: 652809, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34336820

RESUMO

Sperm cells are of unique elongated structure and function, the development of which is tightly regulated by the existing proteins and the posttranslational modifications (PTM) of these proteins. Based on the phylogenetic relationships of various swine breeds, Yorkshire boar is believed to be distinctly different from Duroc boar. The comprehensive differential proteomics and phosphoproteomics profilings were performed on spermatozoa from both Yorkshire and Duroc boars. By both peptide and PTM peptide quantification followed by statistical analyses, 167 differentially expressed proteins were identified from 1,745 proteins, and 283 differentially expressed phosphopeptides corresponding to 102 unique differentially phosphorylated proteins were measured from 1,140 identified phosphopeptides derived from 363 phosphorylated proteins. The representative results were validated by Western blots. Pathway enrichment analyses revealed that majority of differential expression proteins and differential phosphorylation proteins were primarily concerned with spermatogenesis, male gamete generation, sperm motility, energy metabolism, cilium morphogenesis, axonemal dynein complex assembly, sperm-egg recognition, and capacitation. Remarkably, axonemal dynein complex assembly related proteins, such as SMCP, SUN5, ODF1, AKAP3, and AKAP4 that play a key regulatory role in the sperm physiological functions, were significantly higher in Duroc spermatozoa than that of Yorkshire. Furthermore, phosphorylation of sperm-specific proteins, such as CABYR, ROPN1, CALM1, PRKAR2A, and PRKAR1A, participates in regulation of the boar sperm motility mainly through the cAMP/PKA signal pathway in different breeds, demonstrating that protein phosphorylation may be an important mechanism underlying the sperm diversity. Protein-protein interaction analysis revealed that the 14 overlapped proteins between differential expression proteins and differential phosphorylation proteins potentially played a key role in sperm development and motility of the flagellum, including the proteins ODF1, SMCP, AKAP4, FSIP2, and SUN5. Taken together, these physiologically and functionally differentially expressed proteins (DEPs) and differentially expressed phosphorylated proteins (DPPs) may constitute the proteomic backgrounds between the two different boar breeds. The validation will be performed to delineate the roles of these PTM proteins as modulators of Yorkshire and Duroc boar spermatozoa.

9.
Adv Mater ; 33(39): e2103000, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34397123

RESUMO

The competing and non-equilibrium phase transitions, involving dynamic tunability of cooperative electronic and magnetic states in strongly correlated materials, show great promise in quantum sensing and information technology. To date, the stabilization of transient states is still in the preliminary stage, particularly with respect to molecular electronic solids. Here, a dynamic and cooperative phase in potassium-7,7,8,8-tetracyanoquinodimethane (K-TCNQ) with the control of pulsed electromagnetic excitation is demonstrated. Simultaneous dynamic and coherent lattice perturbation with 8 ns pulsed laser (532 nm, 15 MW cm-2 , 10 Hz) in such a molecular electronic crystal initiates a stable long-lived (over 400 days) conducting paramagnetic state (≈42 Ωcm), showing the charge-spin bistability over a broad temperature range from 2 to 360 K. Comprehensive noise spectroscopy, in situ high-pressure measurements, electron spin resonance (ESR), theoretical model, and scanning tunneling microscopy/spectroscopy (STM/STS) studies provide further evidence that such a transition is cooperative, requiring a dedicated charge-spin-lattice decoupling to activate and subsequently stabilize nonequilibrium phase. The cooperativity triggered by ultrahigh-strain-rate (above 106 s- 1 ) pulsed excitation offers a collective control toward the generation and stabilization of strongly correlated electronic and magnetic orders in molecular electronic solids and offers unique electro-magnetic phases with technological promises.

10.
Med Phys ; 48(9): 4784-4798, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34245602

RESUMO

PURPOSE: Radiotherapy presents unique challenges and clinical requirements for longitudinal tumor and organ-at-risk (OAR) prediction during treatment. The challenges include tumor inflammation/edema and radiation-induced changes in organ geometry, whereas the clinical requirements demand flexibility in input/output sequence timepoints to update the predictions on rolling basis and the grounding of all predictions in relationship to the pre-treatment imaging information for response and toxicity assessment in adaptive radiotherapy. METHODS: To deal with the aforementioned challenges and to comply with the clinical requirements, we present a novel 3D sequence-to-sequence model based on Convolution Long Short-Term Memory (ConvLSTM) that makes use of series of deformation vector fields (DVFs) between individual timepoints and reference pre-treatment/planning CTs to predict future anatomical deformations and changes in gross tumor volume as well as critical OARs. High-quality DVF training data are created by employing hyper-parameter optimization on the subset of the training data with DICE coefficient and mutual information metric. We validated our model on two radiotherapy datasets: a publicly available head-and-neck dataset (28 patients with manually contoured pre-, mid-, and post-treatment CTs), and an internal non-small cell lung cancer dataset (63 patients with manually contoured planning CT and 6 weekly CBCTs). RESULTS: The use of DVF representation and skip connections overcomes the blurring issue of ConvLSTM prediction with the traditional image representation. The mean and standard deviation of DICE for predictions of lung GTV at weeks 4, 5, and 6 were 0.83 ± 0.09, 0.82 ± 0.08, and 0.81 ± 0.10, respectively, and for post-treatment ipsilateral and contralateral parotids, were 0.81 ± 0.06 and 0.85 ± 0.02. CONCLUSION: We presented a novel DVF-based Seq2Seq model for medical images, leveraging the complete 3D imaging information of a relatively large longitudinal clinical dataset, to carry out longitudinal GTV/OAR predictions for anatomical changes in HN and lung radiotherapy patients, which has potential to improve RT outcomes.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radioterapia de Intensidade Modulada , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Órgãos em Risco , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador
11.
Med Phys ; 48(9): 5130-5141, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34245012

RESUMO

PURPOSE: In current clinical practice, noisy and artifact-ridden weekly cone beam computed tomography (CBCT) images are only used for patient setup during radiotherapy. Treatment planning is performed once at the beginning of the treatment using high-quality planning CT (pCT) images and manual contours for organs-at-risk (OARs) structures. If the quality of the weekly CBCT images can be improved while simultaneously segmenting OAR structures, this can provide critical information for adapting radiotherapy mid-treatment as well as for deriving biomarkers for treatment response. METHODS: Using a novel physics-based data augmentation strategy, we synthesize a large dataset of perfectly/inherently registered pCT and synthetic-CBCT pairs for locally advanced lung cancer patient cohort, which are then used in a multitask three-dimensional (3D) deep learning framework to simultaneously segment and translate real weekly CBCT images to high-quality pCT-like images. RESULTS: We compared the synthetic CT and OAR segmentations generated by the model to real pCT and manual OAR segmentations and showed promising results. The real week 1 (baseline) CBCT images which had an average mean absolute error (MAE) of 162.77 HU compared to pCT images are translated to synthetic CT images that exhibit a drastically improved average MAE of 29.31 HU and average structural similarity of 92% with the pCT images. The average DICE scores of the 3D OARs segmentations are: lungs 0.96, heart 0.88, spinal cord 0.83, and esophagus 0.66. CONCLUSIONS: We demonstrate an approach to translate artifact-ridden CBCT images to high-quality synthetic CT images, while simultaneously generating good quality segmentation masks for different OARs. This approach could allow clinicians to adjust treatment plans using only the routine low-quality CBCT images, potentially improving patient outcomes. Our code, data, and pre-trained models will be made available via our physics-based data augmentation library, Physics-ArX, at https://github.com/nadeemlab/Physics-ArX.


Assuntos
Tomografia Computadorizada de Feixe Cônico Espiral , Tomografia Computadorizada de Feixe Cônico , Humanos , Processamento de Imagem Assistida por Computador , Órgãos em Risco , Física , Planejamento da Radioterapia Assistida por Computador
12.
Front Pharmacol ; 12: 655836, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122077

RESUMO

Background: Immunosuppressive medication (IM) nonadherence is associated with poor transplant outcomes. Therefore, it is of great importance to identify predictive factors with IM nonadherence. We aimed to improve the predicted capacity of the theory of planned behavior (TPB) by adding health belief model's (HBM) variables in renal transplant patients (RTPs). Methods: This cross-sectional study distributed questionnaires to patients who had undergone renal transplant and follow-up regularly in the transplant center of Third Xiangya Hospital in China. The self-developed questionnaire collected data in three aspects: general data questionnaire, TPB, HBM-specific questionnaire, and Basel Assessment of Adherence to Immunosuppressive Medications scale. Results: A total of 1,357 of 1,480 patients completed the survey, with a participation rate of 91.69% and IM nonadherence rate of 33.53%. The marital status, household income, preoperative drinking history, the time after transplantation, and religion showed independent predictive factors with IM nonadherence (p < 0.05). Strikingly, adding HBM variables to the TPB theory model significantly increased its prediction ability to IM nonadherence (52%). Also, HBM manifested the highest coefficient of effect (-0.620). Particularly, perceived barriers and perceived seriousness, the variables of the HBM model, played a vital influence on medication nonadherence (-0.284 and 0.256). Conclusion: Our study here reveals the first investigation of the combined effects of the TPB and HBM model on IM nonadherence in Chinese RTPs, which could significantly improve the predictive ability of any single model. Meanwhile, future interventions should be conducted to both increase perceived seriousness and reduce perceived barriers for taking IM, which will effectively decrease IM nonadherence rates and improve transplant outcomes.

14.
Anal Methods ; 13(29): 3242-3248, 2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-34184005

RESUMO

A simple and sensitive method for the simultaneous determination of chito-oligosaccharides (COSs) with degrees of polymerization (DPs) from 2 to 7 was developed and used for COS quantification in rat plasma. Samples were separated on a Waters XBridge Amide column (3.5 µm, 2.1 × 150 mm) by isometric elution with 10 mM aqueous ammonium acetate (pH = 9) in acetonitrile and 10 mM aqueous ammonium acetate (pH = 9) (v/v, 50 : 50) employing multiple reaction monitoring (MRM) detection. Analytes and internal standards (IS) were extracted from rat plasma by protein precipitation with acetonitrile. The assay was linear over a concentration range of 20-10 000 ng mL-1 for COS2-7. The intra-day and inter-day precision of the investigated components exhibited an RSD within 15%, and the accuracy (RE%) ranged from -7.3% to 7.6%. The extraction recoveries of the six constituents were determined to be between 82.5% and 94.3%. No significant matrix effects for COS2-7 were observed in rat plasma. COS in plasma remained stable for 24 h at room temperature (short-term), after freeze-thaw cycles, and 30 days in a -40 °C freezer. In comparison to reported COS quantitation methods, this method is simple, sensitive and cost-effective and could be used for the simultaneous quantitation of COS2-7. This method meets the Food and Drug Administration guidelines and had been successfully applied to the analysis of pharmacokinetic samples collected from rats.


Assuntos
Plasma , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida , Oligossacarídeos , Ratos , Reprodutibilidade dos Testes , Estados Unidos
15.
Life (Basel) ; 11(4)2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33810453

RESUMO

Upon exposure of photosynthetic organisms to high light (HL), several HL acclimation responses are triggered. Herein, we identified a novel gene, slr0320, critical for HL acclimation in Synechocystis sp. PCC 6803. The growth rate of the Δslr0320 mutant was similar to wild type (WT) under normal light (NL) but severely declined under HL. Net photosynthesis of the mutant was lower under HL, but maximum photosystem II (PSII) activity was higher under NL and HL. Immunodetection revealed the accumulation and assembly of PSII were similar between WT and the mutant. Chlorophyll fluorescence traces showed the stable fluorescence of the mutant under light was much higher. Kinetics of single flash-induced chlorophyll fluorescence increase and decay revealed the slower electron transfer from QA to QB in the mutant. These data indicate that, in the Δslr0320 mutant, the number of functional PSIIs was comparable to WT even under HL but the electron transfer between QA and QB was inefficient. Quantitative proteomics and real-time PCR revealed that expression profiles of psbL, psbH and psbI were significantly altered in the Δslr0320 mutant. Thus, Slr0320 protein plays critical roles in optimizing PSII activity during HL acclimation and is essential for PSII electron transfer from QA to QB.

16.
ACS Nano ; 15(4): 7586-7595, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33821627

RESUMO

The two-dimensional (2D) lamellar membrane assembly technique shows substantial potential for sustainable desalination applications. However, the relatively wide and size-variable channels of 2D membranes in aqueous solution result in inferior salt rejections. Here we show the establishment of nanofluidic heterostructured channels in graphene oxide (GO) membranes by adding g-C3N4 sheets into GO interlamination. Benefiting from the presence of stable and sub-nanometer wide (0.42 nm) GO/g-C3N4 channels, the GO/g-C3N4 membrane exhibits salt rejections of ∼90% with water permeances of above 30 L h-1 m-2 bar-1, while the pure GO membrane only has salt rejections of below 30% accompanied by water permeances of below 4 L h-1 m-2 bar-1. Combining experimental and theoretical investigations, size exclusion has proved to be the dominating mechanism for high rejections, and the ultralow friction water flow along g-C3N4 sheets is responsible for permeation enhancements. Importantly, the GO/g-C3N4 membrane shows promising long-term, antioxidation, and antipressure stability.

17.
Front Microbiol ; 12: 649390, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33821158

RESUMO

The emergence and dissemination of bacterial infections is paralyzing our public health systems worldwide. Worse still, there are no effective antibiotics against bacterial toxins, which facilitate the infection. Natural herbs that target bacterial toxins may be a better choice for therapy of infectious diseases. However, most natural drugs present unknown compositions and unclear mechanisms. Here we demonstrated that the Chinese herb Paeoniae Radix aqueous extract (PRAE) could suppress alpha-toxin (α-toxin) of Staphylococcus aureus. We observed that the paeoniflorin derivative (PRAE-a) derivative in PRAE significantly abolished the hemolytic activity of S. aureus α-toxin. The analyses of high-performance liquid chromatography (HPLC), mass spectrometer (MS), Fourier transform infrared spectrometer (FTIR), and nuclear magnetic resonance (NMR) showed that PRAE-a was a glycoside compound with a paeoniflorin nucleus. We further found that PRAE-a disrupted the pore-forming ability of α-toxin by prevention of the dimer to heptamer. Therefore, PRAE-a proved to be an effective therapy for S. aureus lung infections in mice by inhibiting α-toxin. Collectively, these results highlighted that PRAE-a can be used as an antibacterial agent to attenuate S. aureus virulence by targeting α-toxin.

18.
Phys Med Biol ; 66(6): 065008, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33535199

RESUMO

Automated segmentation of the esophagus is critical in image-guided/adaptive radiotherapy of lung cancer to minimize radiation-induced toxicities such as acute esophagitis. We have developed a semantic physics-based data augmentation method for segmenting the esophagus in both planning CT (pCT) and cone beam CT (CBCT) using 3D convolutional neural networks. One hundred and ninety-one cases with their pCTs and CBCTs from four independent datasets were used to train a modified 3D U-Net architecture and a multi-objective loss function specifically designed for soft-tissue organs such as the esophagus. Scatter artifacts and noises were extracted from week-1 CBCTs using a power-law adaptive histogram equalization method and induced to the corresponding pCT were reconstructed using CBCT reconstruction parameters. Moreover, we leveraged physics-based artifact induction in pCTs to drive the esophagus segmentation in real weekly CBCTs. Segmentations were evaluated using the geometric Dice coefficient and Hausdorff distance as well as dosimetrically using mean esophagus dose and D 5cc. Due to the physics-based data augmentation, our model trained just on the synthetic CBCTs was robust and generalizable enough to also produce state-of-the-art results on the pCTs and CBCTs, achieving Dice overlaps of 0.81 and 0.74, respectively. It is concluded that our physics-based data augmentation spans the realistic noise/artifact spectrum across patient CBCT/pCT data and can generalize well across modalities, eventually improving the accuracy of treatment setup and response analysis.


Assuntos
Tomografia Computadorizada de Feixe Cônico/métodos , Esôfago/diagnóstico por imagem , Planejamento da Radioterapia Assistida por Computador/métodos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Redes Neurais de Computação
19.
Int J Radiat Oncol Biol Phys ; 110(3): 883-892, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33453309

RESUMO

PURPOSE: Acute esophagitis (AE) is a common dose-limiting toxicity in radiation therapy of locally advanced non-small cell lung cancer (LA-NSCLC). We developed an early AE prediction model from weekly accumulated esophagus dose and its associated local volumetric change. METHODS AND MATERIALS: Fifty-one patients with LA-NSCLC underwent treatment with intensity modulated radiation therapy to 60 Gy in 2-Gy fractions with concurrent chemotherapy and weekly cone beam computed tomography (CBCT). Twenty-eight patients (55%) developed grade ≥2 AE (≥AE2) at a median of 4 weeks after the start of radiation therapy. For early ≥AE2 prediction, the esophagus on CBCT of the first 2 weeks was deformably registered to the planning computed tomography images, and weekly esophagus dose was accumulated. Week 1-to-week 2 (w1→w2) esophagus volume changes including maximum esophagus expansion (MEex%) and volumes with ≥x% local expansions (VEx%; x = 5, 10, 15) were calculated from the Jacobian map of deformation vector field gradients. Logistic regression model with 5-fold cross-validation was built using combinations of the accumulated mean esophagus doses (MED) and the esophagus change parameters with the lowest P value in univariate analysis. The model was validated on an additional 18 and 11 patients with weekly CBCT and magnetic resonance imaging (MRI), respectively, and compared with models using only planned mean dose (MEDPlan). Performance was assessed using area under the curve (AUC) and Hosmer-Lemeshow test (PHL). RESULTS: Univariately, w1→w2 VE10% (P = .004), VE5% (P = .01) and MEex% (P = .02) significantly predicted ≥AE2. A model combining MEDW2 and w1→w2 VE10% had the best performance (AUC = 0.80; PHL = 0.43), whereas the MEDPlan model had a lower accuracy (AUC = 0.67; PHL = 0.26). The combined model also showed high accuracy in the CBCT (AUC = 0.78) and MRI validations (AUC = 0.75). CONCLUSIONS: A CBCT-based, cross-validated, and internally validated model on MRI with a combination of accumulated esophagus dose and local volume change from the first 2 weeks of chemotherapy significantly improved AE prediction compared with conventional models using only the planned dose. This model could inform plan adaptation early to lower the risk of esophagitis.


Assuntos
Esofagite/diagnóstico , Esofagite/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Feminino , Humanos , Modelos Logísticos , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador
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