Design, Synthesis, and Evaluation of [18F]BIBD-300 as a Positron Emission Tomography Tracer for Poly(ADP-Ribose) Polymerase-1.

Compounds 8a-j were designed to adjust the mode of interaction and lipophilicity of FTT by scaffold hopping and changing the length of the alkoxy groups. Compounds 8a, 8d, 8g, and BIBD-300 were screened for high-affinity PARP-1 through enzyme inhibition assays and are worthy of further evaluation. PET imaging of MCF-7 subcutaneous tumors with moderate expression of PARP-1 showed that compared to [18F]FTT, [18F]8a, [18F]8d, and [18F]8g exhibited greater nonspecific uptake, a lower target-to-nontarget ratio, and severe defluorination, while [18F]BIBD-300 exhibited lower nonspecific uptake and a greater target-to-nontarget ratio. PET imaging of 22Rv1 subcutaneous tumors, which highly express PARP-1, confirmed that the uptake of [18F]BIBD-300 in normal organs, such as the liver, muscle, and bone, was lower than that of [18F]FTT, and the ratio of tumor-to-muscle and tumor-to-liver [18F]BIBD-300 was greater than that of [18F]FTT. The biodistribution results in mice with MCF-7 and 22Rv1 subcutaneous tumors further validated the results of PET imaging. Unlike [18F]FTT, which mainly relies on hepatobiliary clearance, [18F]BIBD-300, which has lower lipophilicity, undergoes a partial shift from hepatobiliary to renal clearance, providing the possibility for [18F]BIBD-300 to indicate liver cancer. The difference in the PET imaging results for [18F]FTT, [18F]BIBD-300, and [18F]8j in 22Rv1 mice and the corresponding molecular docking results further confirmed that subtle structural modifications in lipophilicity greatly optimize the properties of the tracer. Cell uptake experiments also demonstrated that [18F]BIBD-300 has a high affinity for PARP-1. Metabolized and unmetabolized [18F]FTT and [18F]BIBD-300 were detected in the brain, indicating that they could not accurately quantify the amount of PARP-1 in the brain. However, PET imaging of glioma showed that both [18F]FTT and [18F]BIBD-300 could accurately localize both in situ to C6 and U87MG tumors. Based on its potential advantages in the diagnosis of breast cancer, prostate cancer, and glioma, as well as liver cancer, [18F]BIBD-300 is a new option for an excellent PARP-1 tracer.

Evaluation of (2S,4S)-4-[18F]FEBGln as a Positron Emission Tomography Tracer for Tumor Imaging.

Glutamine metabolism-related tracers have the potential to visualize numerous tumors because glutamine is the second largest source of energy for tumors. (2S,4S)-4-[18F]FEBGln was designed by introducing [18F]fluoroethoxy benzyl on carbon-4 of glutamine. The aim of this study was to investigate the pharmacokinetic properties and tumor positron emission tomography (PET) imaging characteristics of (2S,4S)-4-[18F]FEBGln in detail. The biodistribution results of nude mice bearing MCF-7 tumor showed that (2S,4S)-4-[18F]FEBGln had high initial tumor uptake, and a fast clearance rate, resulting in a high tumor-to-muscle ratio at 30 min postinjection. There was no obvious defluorination in vivo. The micro-PET-CT imaging results of (2S,4S)-4-[18F]FEBGln orthotopic MCF-7 tumor-bearing nude mice were consistent with the biological distribution results. Compared with (2S,4R)-4-[18F]FGln, (2S,4S)-4-[18F]FEBGln showed poor tumor retention, but its clearance in normal tissues was also fast, so it had better PET image contrast than the former. Unlike poor retention in MCF-7-bearing nude mice, (2S,4S)-4-[18F]FEBGln has good retention in NCI-h1975 and 22Rv1 tumor models. Since (2S,4S)-4-[18F]FEBGln has low uptake in normal lungs and high uptake in the bladder, it is expected to be used in the accurate diagnosis of lung cancer but cannot accurately determine prostate cancer. Consistent with the advantages of radiolabeled amino acids in the application of brain tumors, (2S,4S)-4-[18F]FEBGln accurately diagnoses U87MG glioma with higher contrast than [18F]FET and [18F]FDG, and there is a correlation between (2S,4S)-4-[18F]FEBGln uptake and tumor growth cycle. Further kinetic model analysis showed that (2S,4S)-4-[18F]FEBGln was similar to (2S,4R)-4-[18F]FGln, conforming to the one-compartment model and the Logan graphical model, and was expected to assess the size of the glutamine pool of the tumor. Therefore, (2S,4S)-4-[18F]FEBGln is expected to provide a strong imaging basis for the diagnosis, formulation of personalized plans, and efficacy evaluation of glioma, lung cancer, and breast cancer.

Identification and Validation of a Metabolism-Related Prognostic Signature Associated with M2 Macrophage Infiltration in Gastric Cancer.

High levels of M2 macrophage infiltration invariably contribute to poor cancer prognosis and can be manipulated by metabolic reprogramming in the tumor microenvironment. However, the metabolism-related genes (MRGs) affecting M2 macrophage infiltration and their clinical implications are not fully understood. In this study, we identified 173 MRGs associated with M2 macrophage infiltration in cases of gastric cancer (GC) using the TCGA and GEO databases. Twelve MRGs were eventually adopted as the prognostic signature to develop a risk model. In the high-risk group, the patients showed poorer survival outcomes than patients in the low-risk group. Additionally, the patients in the high-risk group were less sensitive to certain drugs, such as 5-Fluorouracil, Oxaliplatin, and Cisplatin. Risk scores were positively correlated with the infiltration of multiple immune cells, including CD8+ T cells and M2 macrophages. Furthermore, a difference was observed in the expression and distribution between the 12 signature genes in the tumor microenvironment through single-cell sequencing analysis. In vitro experiments proved that the M2 polarization of macrophages was suppressed by Sorcin-knockdown GC cells, thereby hindering the proliferation and migration of GC cells. These findings provide a valuable prognostic signature for evaluating clinical outcomes and corresponding treatment options and identifying potential targets for GC treatment.

Paracandidimonas lactea sp. nov., a urea-utilizing bacterium isolated from landfill.

A urea-utilizing bacterium, designated Q2-2 T, was isolated from landfill. Cells of strain Q2-2 T were Gram stain-negative, aerobic, short-rod bacteria. Strain Q2-2 T was observed to grow at a temperature range of 15-37℃ (optimum 30 â„ƒ), a pH range of 5.5-9.5 (optimum pH 8.0) and 0-4% (w/v) NaCl (optimum 1%). The major respiratory quinone was Q-8, and the major polar lipids were diphosphatidyl glycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine, and phosphatidyl glycerol. Based on the 16S rRNA gene sequence, strain Q2-2 T had the highest similarity with Paracandidimonas caeni 24 T (98.0%), followed by Pusillimonas soli MJ07T (97.5%), Parapusillimonas granuli Ch07T (97.2%), Pusillimonas ginsengisoli DCY25T (97.1%) and Paracandidimonas soli IMT-305 T (96.4%). The ANI values between strain Q2-2 T and the above related type strains were 71.02%, 73.52%, 74.32%, 74.59% and 72.29%, respectively. The DNA G + C content of strain Q2-2 T was 61.1%. Therefore, strain Q2-2 T represents a novel species of the genus Paracandidimonas, for which the name Paracandidimonas lactea sp. nov. (type strain Q2-2 T = CGMCC 1.19179 T = JCM 34906 T) is proposed.

Advancements in Manganese-based Cathode for Sustainable Energy Utilization.

Manganese-based compounds, especially manganese oxides, are one of the most exceptional electrode materials. Specifically, manganese oxides have gained significant interest owing to their unique crystal structures, high theoretical capacity, abundant natural availability and eco-friendly nature. However, as transition metal semiconductors, manganese oxide possess low electrical conductivity, limited rate capacity, and suboptical cycle stability. Thus, combining manganese oxides with carbon or other metallic materials can significantly improve their electrochemical performance. These composites increase active sites and conductivity, thereby improving electrode reaction kinetics, cycle stability, and lifespan of supercapacitors (SCs) and batteries. This paper reviews the latest applications of Mn-based cathodes in SCs and advanced batteries. Moreover, the energy storage mechanisms were also proposed. In this review, the development prospects and challenges for advanced energy storage applications of Mn-based cathodes are summarized.

Cartoon Animation Outpainting With Region-Guided Motion Inference.

Cartoon animation video is a popular visual entertainment form worldwide, however many classic animations were produced in a 4:3 aspect ratio that is incompatible with modern widescreen displays. Existing methods like cropping lead to information loss while retargeting causes distortion. Animation companies still rely on manual labor to renovate classic cartoon animations, which is tedious and labor-intensive, but can yield higher-quality videos. Conventional extrapolation or inpainting methods tailored for natural videos struggle with cartoon animations due to the lack of textures in anime, which affects the motion estimation of the objects. In this paper, we propose a novel framework designed to automatically outpaint 4:3 anime to 16:9 via region-guided motion inference. Our core concept is to identify the motion correspondences between frames within a sequence in order to reconstruct missing pixels. Initially, we estimate optical flow guided by region information to address challenges posed by exaggerated movements and solid-color regions in cartoon animations. Subsequently, frames are stitched to produce a pre-filled guide frame, offering structural clues for the extension of optical flow maps. Finally, a voting and fusion scheme utilizes learned fusion weights to blend the aligned neighboring reference frames, resulting in the final outpainting frame. Extensive experiments confirm the superiority of our approach over existing methods.

Glycine/alginate-based piezoelectric film consisting of a single, monolithic ß-glycine spherulite towards flexible and biodegradable force sensor.

Development of piezoelectric biomaterials with high piezoelectric performance, while possessing excellent flexibility, biocompatibility, and biodegradability still remains a great challenge. Herein, a flexible, biocompatible and biodegradable piezoelectric ß-glycine-alginate-glycerol (Gly-Alg-Glycerol) film with excellent in vitro and in vivo sensing performance was developed. Remarkably, a single, monolithic ß-glycine spherulite, instead of more commonly observed multiple spherulites, was formed in alginate matrix, thereby resulting in outstanding piezoelectric property, including high piezoelectric constant (7.2 pC/N) and high piezoelectric sensitivity (1.97 mV/kPa). The Gly-Alg-Glycerol film exhibited superior flexibility, enabling complex shape-shifting, e.g. origami pigeon, 40% tensile strain, and repeated bending and folding deformation without fracture. In vitro, the flexible Gly-Alg-Glycerol film sensor could detect subtle pulse signal, sound wave and recognize shear stress applied from different directions. In addition, we have demonstrated that the Gly-Alg-Glycerol film sensor sealed by polylactic acid and beeswax could serve as an in vivo sensor to monitor physiological pressure signals such as heartbeat, respiration and muscle movement. Finally, the Gly-Alg-Glycerol film possessed good biocompatibility, supporting the attachment and proliferation of rat mesenchymal stromal cells, and biodegradability, thereby showing great potential as biodegradable piezoelectric biomaterials for biomedical sensing applications.

Design of Novel 18F-Labeled Amino Acid Tracers Using Sulfur 18F-Fluoride Exchange Click Chemistry.

[18F]Gln-OSO2F, [18F]Arg-OSO2F, and [18F]FSY-OSO2F were designed by introducing sulfonyl 18F-fluoride onto glutamine, arginine, and tyrosine, respectively. [18F]FSY-OSO2F can be prepared directly by sulfur 18F-fluoride exchange, while [18F]Gln-OSO2F and [18F]Arg-OSO2F require a two-step labeling method. Those tracers retain their typical transport characteristics for unmodified amino acids. Both PET imaging and biodistribution confirmed that [18F]FSY-OSO2F visualized MCF-7 and 22Rv1 subcutaneous tumors with high contrast, and its tumor-to-muscle ratio was better than that of [18F]FET. However, [18F]Gln-OSO2F and [18F]Arg-OSO2F poorly image MCF-7 subcutaneous tumors, possibly due to differences in the types and amounts of transporters expressed in tumors. All three tracers can visualize the U87MG glioma. According to our biological evaluation, none of the tracers evaluated in this study exhibited obvious defluorination, and subtle structural changes led to different imaging characteristics, indicating that the application of sulfur 18F-fluoride exchange click chemistry in the design of radioactive sulfonyl fluoride amino acids is feasible and offers significant advantages.

Shading-guided Manga Screening from Reference.

Manga screening is a critical process in manga production, which still requires intensive labor and cost. Existing manga screening methods either generate simple dotted screentones only or rely on color information and manual hints during screentone selection. Due to the large domain gap between line drawings and screened manga, and the difficulties in generating high-quality, properly selected and shaded screentones, even state-of-the-art deep learning methods cannot convert line drawings to screened manga well. Besides, ambiguity exists in the screening process since different artists may screen differently for the same line drawing. In this paper, we propose to introduce shaded line drawing as the intermediate counterpart of the screened manga so that the manga screening task can be decomposed into two sub-tasks, generating shading from a line drawing and replacing shading with proper screentones. The reference image is adopted to resolve the ambiguity issue and provides options and controls on the generated screened manga. We proposed a reference-based shading generation network and a reference-based screentone generation module to achieve the two sub-tasks individually. We conduct extensive visual and quantitative experiments to verify the effectiveness of our system. Results and statistics show that our method outperforms existing methods on the manga screening task.

Separating Shading and Reflectance from Cartoon Illustrations.

Shading plays an important role in cartoon drawings to present the 3D lighting and depth information in a 2D image to improve the visual information and pleasantness. But it also introduces apparent challenges in analyzing and processing the cartoon drawings for different computer graphics and vision applications, such as segmentation, depth estimation, and relighting. Extensive research has been made in removing or separating the shading information to facilitate these applications. Unfortunately, the existing researches only focused on natural images, which are natively different from cartoons since the shading in natural images is physically correct and can be modeled based on physical priors. However, shading in cartoons is manually created by artists, which may be imprecise, abstract, and stylized. This makes it extremely difficult to model the shading in cartoon drawings. Without modeling the shading prior, in the paper, we propose a learning-based solution to separate the shading from the original colors using a two-branch system consisting of two subnetworks. To the best of our knowledge, our method is the first attempt in separating shading information from cartoon drawings. Our method significantly outperforms the methods tailored for natural images. Extensive evaluations have been performed with convincing results in all cases.

Panel-Page-Aware Comic Genre Understanding.

Using a sequence of discrete still images to tell a story or introduce a process has become a tradition in the field of digital visual media. With the surge in these media and the requirements in downstream tasks, acquiring their main topics or genres in a very short time is urgently needed. As a representative form of the media, comic enjoys a huge boom as it has gone digital. However, different from natural images, comic images are divided by panels, and the images are not visually consistent from page to page. Therefore, existing works tailored for natural images perform poorly in analyzing comics. Considering the identification of comic genres is tied to the overall story plotting, a long-term understanding that makes full use of the semantic interactions between multi-level comic fragments needs to be fully exploited. In this paper, we propose [Formula: see text]Comic, a Panel-Page-aware Comic genre classification model, which takes page sequences of comics as the input and produces class-wise probabilities. [Formula: see text]Comic utilizes detected panel boxes to extract panel representations and deploys self-attention to construct panel-page understanding, assisted with interdependent classifiers to model label correlation. We develop the first comic dataset for the task of comic genre classification with multi-genre labels. Our approach is proved by experiments to outperform state-of-the-art methods on related tasks. We also validate the extensibility of our network to perform in the multi-modal scenario. Finally, we show the practicability of our approach by giving effective genre prediction results for whole comic books.

Design, Synthesis, and Biological Evaluation of a Novel [18F]-Labeled Arginine Derivative for Tumor Imaging.

To better diagnose and treat tumors related to arginine metabolism, (2S,4S)-2-amino-4-(4-(2-(fluoro-18F)ethoxy)benzyl)-5-guanidinopentanoic acid ([18F]7) was designed and prepared by introducing [18F]fluoroethoxy benzyl on carbon-4 of arginine. [18F]7 and 7 were successfully prepared using synthesis methods similar to those used for (2S,4S)-4-[18F]FEBGln and (2S,4S)-4-FEBGln, respectively. In vitro experiments on cell transport mechanisms showed that [18F]7 was similar to (2S,4S)4-[18F]FPArg and was transported into tumor cells by cationic amino acid transporters. However, [18F]7 can also enter MCF-7 cells via ASC and ASC2 amino acid transporters. Further microPET-CT imaging showed that the initial uptake and retention properties of [18F]7 in MCF-7 subcutaneous tumors were good (2.29 ± 0.09%ID/g at 2.5 min and 1.71 ± 0.09%ID/g at 60 min after administration), without significant defluorination in vivo. However, compared to (2S,4S)4-[18F]FPArg (3.06 ± 0.59%ID/g at 60 min after administration), [18F]7 exhibited lower tumor uptake and higher nonspecific uptake. When further applied to U87MG imaging, [18F]7 can quickly visualize brain gliomas (tumor-to-brain, 1.85 at 60 min after administration). Therefore, based on the above results, [18F]7 will likely be applied for the diagnosis of arginine nutrition-deficient tumors and efficacy evaluations.

Development and Preclinical Evaluation of [68Ga]BMSH as a New Potent Positron Emission Tomography Tracer for Imaging Programmed Death-Ligand 1 Expression.

Immunotherapy targeting the programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) pathway has shown remarkable efficacy against various cancers, but the overall response rate (ORR) is still low. PD-L1 expression in tumors may predict treatment response to immunotherapy. Indeed, ongoing clinical studies utilize a few PD-L1 radiotracers to assess PD-L1 expression as a predictive biomarker for immunotherapy. Here, we present a novel positron emission tomography (PET) radiotracer called [68Ga]BMSH, which is derived from a small molecule inhibitor specifically targeting the binding site of PD-L1. The inhibitor was modified to optimize its in vivo pharmacokinetic properties and enable chelation of 68Ga. In vitro evaluation revealed [68Ga]BMSH possessed a strong binding affinity, high specificity, and rapid internalization in PD-L1 overexpressing cells. Biodistribution studies showed that PD-L1 overexpressing tumors had an uptake of [68Ga]BMSH at 4.22 ± 0.65%ID/g in mice, while the number was 2.23 ± 0.41%ID/g in PD-L1 low-expressing tumors. Micro-PET/CT imaging of tumor-bearing mice further confirmed that, compared to [18F]FDG, [68Ga]BMSH can specifically identify tumors with varying levels of PD-L1 expression. Our findings suggest that the [68Ga]BMSH is a PD-L1 radioligand with ideal imaging properties, and its further application in the clinical screening of PD-L1 overexpressing tumors may improve ORR for immunotherapy.

The chromosome-scale genome assembly of the yellowtail clownfish Amphiprion clarkii provides insights into the melanic pigmentation of anemonefish.

Anemonefish are an emerging group of model organisms for studying genetic, ecological, evolutionary, and developmental traits of coral reef fish. The yellowtail clownfish Amphiprion clarkii possesses species-specific characteristics such as inter-species co-habitation, high intra-species color variation, no anemone specificity, and a broad geographic distribution, that can increase our understanding of anemonefish evolutionary history, behavioral strategies, fish-anemone symbiosis, and color pattern evolution. Despite its position as an emerging model species, the genome of A. clarkii is yet to be published. Using PacBio long-read sequencing and Hi-C chromatin capture technology, we generated a high-quality chromosome-scale genome assembly initially comprised of 1,840 contigs with an N50 of 1,203,211 bp. These contigs were successfully anchored into 24 chromosomes of 843,582,782 bp and annotated with 25,050 protein-coding genes encompassing 97.0% of conserved actinopterygian genes, making the quality and completeness of this genome the highest among all published anemonefish genomes to date. Transcriptomic analysis identified tissue-specific gene expression patterns, with the brain and optic lobe having the largest number of expressed genes. Further analyses revealed higher copy numbers of erbb3b (a gene involved in melanocyte development) in A. clarkii compared with other anemonefish, thus suggesting a possible link between erbb3b and the natural melanism polymorphism observed in A. clarkii. The publication of this high-quality genome, along with A. clarkii's many unique traits, position this species as an ideal model organism for addressing scientific questions across a range of disciplines.

Revision and validation of the prosocialness scale for adults (PSA) among chinese college students.

BACKGROUND: Although prosocial behavior plays an important role in the development of individuals, there are few prosocial measurements for college students. This study examines the applicability of the Prosocialness Scale for Adults to a sample of Chinese college students and provides a measurement tool for prosocial behavior among Chinese college students. METHODS: Three sub-studies were conducted in this study to revise the Prosocialness Scale for Adults (PSA) and verify its applicability in Chinese college students. In Study 1, the translated Prosocialness Scale for Adults (PSA) was used to test (N = 436). In Study 2, confirmatory factor analysis was carried out (N = 576). The Scale of School Adjustment for College Students, the Scale of Regulatory Emotional Self-Efficacy, the Prosocial Tendencies Measure, and the Chinese Big Five Personality Inventory were used to test the concurrent validity. And the internal consistency reliability of the scale was tested. In Study 3, the test-retest reliability of the scale was tested 4 weeks after the completion of Study 2. RESULTS: The results show that the scale has a good single-factor structure (χ2/df = 4.180, CFI = 0.936, TLI = 0.922, GFI = 0.937, IFI = 0.937, NFI = 0.919, AGFI = 0.907, RMSEA = 0.074, SRMR = 0.042). The total score was positively correlated with the scores of the Scale of Regulatory Emotional Self-Efficacy (r = 0.394, p < 0.001), the Scale of School Adjustment for College Students (r = 0.429, p < 0.001), the Chinese Big Five Personality Inventory (r = 0.456, p < 0.001) ,and the Prosocial Tendencies Measure (r = 0.619, p < 0.001). The internal consistency reliability was robust (α = 0.890) and the test-retest reliability was 0.801. CONCLUSION: These studies show that the Chinese version of the Prosocialness Scale for Adults (PSA) has good reliability and validity and can be used to measure the prosocial behavior of Chinese college students.

Design, Synthesis, and Evaluation of 18F-Labeled Tracers Targeting Fibroblast Activation Protein for Brain Imaging.

Fibroblast activation protein (FAP) is closely related to central nervous system diseases such as stroke and brain tumors, but PET tracers that can be used for brain imaging have not been reported. Here, we designed, synthesized, and evaluated 18F-labeled UAMC1110 derivatives suitable for brain imaging targeting FAP. By substituting the F atom for the H atom on the aromatic ring of compound UAMC1110, 1a-c were designed and prepared. 1a-c were confirmed to have a high affinity for FAP through molecular docking and enzyme assay. [18F]1a-c were successfully prepared and confirmed to have high affinity. The stability in vivo indicates that no obvious metabolites of [18F]1a,b were found in the plasma 1 h after injection, which is beneficial for brain imaging. In vitro cell uptake experiments showed that [18F]1a,b and [68Ga]FAPI04 exhibited similar uptake and internalization rates. PET imaging of U87MG subcutaneous tumor showed that [18F]1a,b could penetrate the blood-brain barrier with higher uptake and longer retention time than [68Ga]FAPI04 (uptake at 62.5 min, 1.06 ± 0.23, 1.09 ± 0.25% ID/g vs 0.21 ± 0.10% ID/g, respectively). The brain-to-blood ratios of [18F]1a,b were better than [68Ga]FAPI04. Biodistribution and PET imaging showed that [18F]1a had better uptake on tumors and a higher tumor-to-muscle ratio than [18F]1b and [68Ga]FAPI04. Further imaging of U87MG intracranial glioma showed that [18F]1a outlined high-contrast gliomas in a short period of time compared to [18F]1b. Therefore, [18F]1a is expected to be useful in the diagnosis of FAP-related brain diseases.

Appearance-preserved Portrait-to-anime Translation via Proxy-guided Domain Adaptation.

Converting a human portrait to anime style is a desirable but challenging problem. Existing methods fail to resolve this problem due to the large inherent gap between two domains that cannot be overcome by a simple direct mapping. For this reason, these methods struggle to preserve the appearance features in the original photo. In this paper, we discover an intermediate domain, the coser portrait (portraits of humans costuming as anime characters), that helps bridge this gap. It alleviates the learning ambiguity and loosens the mapping difficulty in a progressive manner. Specifically, we start from learning the mapping between coser and anime portraits, and present a proxy-guided domain adaptation learning scheme with three progressive adaptation stages to shift the initial model to the human portrait domain. In this way, our model can generate visually pleasant anime portraits with well-preserved appearances given the human portrait. Our model adopts a disentangled design by breaking down the translation problem into two specific subtasks of face deformation and portrait stylization. This further elevates the generation quality. Extensive experimental results show that our model can achieve visually compelling translation with better appearance preservation and perform favorably against the existing methods both qualitatively and quantitatively. Our code and datasets are available at https://github.com/NeverGiveU/PDA-Translation.

Optimization of Precursor Synthesis Conditions of (2S,4S)4-[18F]FPArg and Its Application in Glioma Imaging.

Although the tracer (2S,4S)4-[18F]FPArg is expected to provide a powerful imaging method for the diagnosis and treatment of clinical tumors, it has not been realized due to the low yield of chemical synthesis and radiolabeling. A simple synthetic method for the radiolabeled precursor of (2S,4S)4-[18F]FPArg in stable yield was obtained by adjusting the sequence of the synthetic steps. Furthermore, the biodistribution experiments confirmed that (2S,4S)4-[18F]FPArg could be cleared out quickly in wild type mouse. Cell uptake experiments and U87MG tumor mouse microPET-CT imaging experiments showed that the tumor had high uptake of (2S,4S)4-[18F]FPArg and the clearance was slow, but (2S,4S)4-[18F]FPArg was rapidly cleared in normal brain tissue. MicroPET-CT imaging of nude mice bearing orthotopic HS683-Luc showed that (2S,4S)4-[18F]FPArg can penetrate blood-brain barrier and image gliomas with a high contrast. Therefore, (2S,4S)4-[18F]FPArg is expected to be further applied in the diagnosis and efficacy evaluation of clinical glioma.

Patient-specific daily updated deep learning auto-segmentation for MRI-guided adaptive radiotherapy.

BACKGROUND AND PURPOSE: Deep Learning (DL) technique has shown great potential but still has limited success in online contouring for MR-guided adaptive radiotherapy (MRgART). This study proposed a patient-specific DL auto-segmentation (DLAS) strategy using the patient's previous images and contours to update the model and improve segmentation accuracy and efficiency for MRgART. METHODS AND MATERIALS: A prototype model was trained for each patient using the first set of MRI and corresponding contours as inputs. The patient-specific model was updated after each fraction with all the available fractional MRIs/contours, and then used to predict the segmentation for the next fraction. During model training, a variant was fitted under consistency constraints, limiting the differences in the volume, length and centroid between the predictions for the latest MRI within a reasonable range. The model performance was evaluated for both organ-at-risks and tumors auto-segmentation for a total of 6 abdominal/pelvic cases (each with at least 8 sets of MRIs/contours) underwent MRgART through Dice Similarity Coefficient (DSC) and 95% Hausdorff Distance (HD95), and was compared with deformable image registration (DIR) and frozen DL model (no updating after pre-training). The contouring time was also recorded and analyzed. RESULTS: The proposed model achieved superior performance with higher mean DSC (0.90, 95 % CI: 0.88-0.95), as compared to DIR (0.63, 95 %CI: 0.59-0.68) and frozen DL models (0.74, 95 % CI: 0.71-0.79). As for tumors, the proposed method yielded a median DSC of 0.95, 95 % CI: 0.94-0.97, and a median HD95 of 1.63 mm, 95 % CI: 1.22 mm-2.06 mm. The contouring time was reduced significantly (p < 0.05) using the proposed method (73.4 ± 6.5 secs) compared to the manual process (12 âˆ¼ 22 mins). The online ART time was reduced to 1650 ± 274 seconds with the proposed method, as compared to 3251.8 ± 447 seconds using the original workflow. CONCLUSION: The proposed patient-specific DLAS method can significantly improve the segmentation accuracy and efficiency for longitudinal MRIs, thereby facilitating the routine practice of MRgART.

Qu-Du-San-Jie decoction induces growth inhibition and vascular normalization in NF2-associated vestibular schwannoma.

Background: Neurofibromatosis type 2 (NF2) is a rare genetic syndrome that predisposes individuals to develop bilateral vestibular schwannomas (VSs) causing a high risk of life-threatening neurological complications. Traditional treatment options for NF2-associated VS usually cause neurological damage, and to date, there are no FDA-approved pharmacotherapies for NF2. The aim of this study was to evaluate the antitumor efficacy of Qu-Du-San-Jie (QDSJ) decoction, a traditional Chinese medicine formula, on NF2-associated VS and to investigate the potential underlying mechanisms. Methods: Ultra high-performance liquid chromatography-mass spectroscopy (UHPLC-MS) analysis was performed to identify the components of QDSJ and their targets. To determine the relationships between the putative targets of QDSJ and the differential genes of NF2-associated VS, the drug-disease crossover genes were screened using the UHPLC-MS data combined with our previous gene expression profiling data. The differentially expressed genes were imported into the STRING database to generate a PPI network. Differentially expressed gene targets and pathways were identified using GO and KEGG pathway enrichment analyses. The in vitro and in vivo drug efficacy of QDSJ decoction was tested using a patient-derived schwannoma cell line and a patient-derived xenograft mouse model, respectively. H&E staining, immunochemistry, and immunofluorescence staining were used to evaluate the cell proliferation and tumor vessels. Results: A total of 133 compounds were identified in QDSJ decoction using UHPLC-MS analysis. Network pharmacology showed that the regulation of necroptosis, apoptosis, cell cycle, angiogenesis, adherens junction, and neuroactive ligand-receptor interaction could be associated with the efficacy of QDSJ in treating NF2-associated VS. Treatment with QDSJ induced necrotic cell death and apoptosis of schwannoma cells in vitro and suppressed the tumor growth in vivo. Histopathological analysis revealed areas of cell necrosis and enlarged tumor blood vessels in the QDSJ-treated tumors. The numbers of cells positive for Cyclin D1 and Ki-67 were significantly reduced in QDSJ-treated tumors compared to control tumors. Immunofluorescence staining of CD31 and αSMA showed a decreased number and density of tumor vessels and normalized vessel structure in QDSJ-treated tumors. Conclusion: Our study demonstrates that QDSJ decoction shows significant antitumor activity against NF2-associated schwannoma and is a possible candidate for future clinical trials.