Unveiling biosynthetic potential of an Arctic marine-derived strain Aspergillus sydowii MNP-2.

BACKGROUND: A growing number of studies have demonstrated that the polar regions have the potential to be a significant repository of microbial resources and a potential source of active ingredients. Genome mining strategy plays a key role in the discovery of bioactive secondary metabolites (SMs) from microorganisms. This work highlighted deciphering the biosynthetic potential of an Arctic marine-derived strain Aspergillus sydowii MNP-2 by a combination of whole genome analysis and antiSMASH as well as feature-based molecular networking (MN) in the Global Natural Products Social Molecular Networking (GNPS). RESULTS: In this study, a high-quality whole genome sequence of an Arctic marine strain MNP-2, with a size of 34.9 Mb was successfully obtained. Its total number of genes predicted by BRAKER software was 13,218, and that of non-coding RNAs (rRNA, sRNA, snRNA, and tRNA) predicted by using INFERNAL software was 204. AntiSMASH results indicated that strain MNP-2 harbors 56 biosynthetic gene clusters (BGCs), including 18 NRPS/NRPS-like gene clusters, 10 PKS/PKS-like gene clusters, 8 terpene synthse gene clusters, 5 indole synthase gene clusters, 10 hybrid gene clusters, and 5 fungal-RiPP gene clusters. Metabolic analyses of strain MNP-2 grown on various media using GNPS networking revealed its great potential for the biosynthesis of bioactive SMs containing a variety of heterocyclic and bridge-ring structures. For example, compound G-8 exhibited a potent anti-HIV effect with an IC50 value of 7.2 nM and an EC50 value of 0.9 nM. Compound G-6 had excellent in vitro cytotoxicities against the K562, MCF-7, Hela, DU145, U1975, SGC-7901, A549, MOLT-4, and HL60 cell lines, with IC50 values ranging from 0.10 to 3.3 µM, and showed significant anti-viral (H1N1 and H3N2) activities with IC50 values of 15.9 and 30.0 µM, respectively. CONCLUSIONS: These findings definitely improve our knowledge about the molecular biology of genus A. sydowii and would effectively unveil the biosynthetic potential of strain MNP-2 using genomics and metabolomics techniques.

Maximizing microcalcification detectability in low-dose dedicated cone-beam breast CT: parallel cascades-based theoretical analysis.

Purpose: We aim to determine the combination of X-ray spectrum and detector scintillator thickness that maximizes the detectability of microcalcification clusters in dedicated cone-beam breast CT. Approach: A cascaded linear system analysis was implemented in the spatial frequency domain and was used to determine the detectability index using numerical observers for the imaging task of detecting a microcalcification cluster with 0.17 mm diameter calcium carbonate spheres. The analysis considered a thallium-doped cesium iodide scintillator coupled to a complementary metal-oxide semiconductor detector and an analytical filtered-back-projection reconstruction algorithm. Independent system parameters considered were the scintillator thickness, applied X-ray tube voltage, and X-ray beam filtration. The combination of these parameters that maximized the detectability index was considered optimal. Results: Prewhitening, nonprewhitening, and nonprewhitening with eye filter numerical observers indicate that the combination of 0.525 to 0.6 mm thick scintillator, 70 kV, and 0.25 to 0.4 mm added copper filtration maximized the detectability index at a mean glandular dose (MGD) of 4.5 mGy. Conclusion: Using parallel cascade systems' analysis, the combination of parameters that could maximize the detection of microcalcifications was identified. The analysis indicates that a harder beam than that used in current practice may be beneficial for the task of detecting microcalcifications at an MGD suitable for breast cancer screening.

An attenuation field network for dedicated cone beam breast CT with short scan and offset detector geometry.

The feasibility of full-scan, offset-detector geometry cone-beam CT has been demonstrated for several clinical applications. For full-scan acquisition with offset-detector geometry, data redundancy from complementary views can be exploited during image reconstruction. Envisioning an upright breast CT system, we propose to acquire short-scan data in conjunction with offset-detector geometry. To tackle the resulting incomplete data, we have developed a self-supervised attenuation field network (AFN). AFN leverages the inherent redundancy of cone-beam CT data through coordinate-based representation and known imaging physics. A trained AFN can query attenuation coefficients using their respective coordinates or synthesize projection data including the missing projections. The AFN was evaluated using clinical cone-beam breast CT datasets (n = 50). While conventional analytical and iterative reconstruction methods failed to reconstruct the incomplete data, AFN reconstruction was not statistically different from the reference reconstruction obtained using full-scan, full-detector data in terms of image noise, image contrast, and the full width at half maximum of calcifications. This study indicates the feasibility of a simultaneous short-scan and offset-detector geometry for dedicated breast CT imaging. The proposed AFN technique can potentially be expanded to other cone-beam CT applications.

Dedicated Cone-Beam Breast CT: Reproducibility of Volumetric Glandular Fraction with Advanced Image Reconstruction Methods.

Dedicated cone-beam breast computed tomography (CBBCT) is an emerging modality and provides fully three-dimensional (3D) images of the uncompressed breast at an isotropic voxel resolution. In an effort to translate this modality to breast cancer screening, advanced image reconstruction methods are being pursued. Since radiographic breast density is an established risk factor for breast cancer and CBBCT provides volumetric data, this study investigates the reproducibility of the volumetric glandular fraction (VGF), defined as the proportion of fibroglandular tissue volume relative to the total breast volume excluding the skin. Four image reconstruction methods were investigated: the analytical Feldkamp-Davis-Kress (FDK), a compressed sensing-based fast, regularized, iterative statistical technique (FRIST), a fully supervised deep learning approach using a multi-scale residual dense network (MS-RDN), and a self-supervised approach based on Noise-to-Noise (N2N) learning. Projection datasets from 106 women who participated in a prior clinical trial were reconstructed using each of these algorithms at a fixed isotropic voxel size of (0.273 mm3). Each reconstructed breast volume was segmented into skin, adipose, and fibroglandular tissues, and the VGF was computed. The VGF did not differ among the four reconstruction methods (p = 0.167), and none of the three advanced image reconstruction algorithms differed from the standard FDK reconstruction (p > 0.862). Advanced reconstruction algorithms developed for low-dose CBBCT reproduce the VGF to provide quantitative breast density, which can be used for risk estimation.

Tracking by segmentation with future motion estimation applied to person-following robots.

Person-following is a crucial capability for service robots, and the employment of vision technology is a leading trend in building environmental understanding. While most existing methodologies rely on a tracking-by-detection strategy, which necessitates extensive datasets for training and yet remains susceptible to environmental noise, we propose a novel approach: real-time tracking-by-segmentation with a future motion estimation framework. This framework facilitates pixel-level tracking of a target individual and predicts their future motion. Our strategy leverages a single-shot segmentation tracking neural network for precise foreground segmentation to track the target, overcoming the limitations of using a rectangular region of interest (ROI). Here we clarify that, while the ROI provides a broad context, the segmentation within this bounding box offers a detailed and more accurate position of the human subject. To further improve our approach, a classification-lock pre-trained layer is utilized to form a constraint that curbs feature outliers originating from the person being tracked. A discriminative correlation filter estimates the potential target region in the scene to prevent foreground misrecognition, while a motion estimation neural network anticipates the target's future motion for use in the control module. We validated our proposed methodology using the VOT, LaSot, YouTube-VOS, and Davis tracking datasets, demonstrating its effectiveness. Notably, our framework supports long-term person-following tasks in indoor environments, showing promise for practical implementation in service robots.

Cancellation of streak artifacts in radial abdominal imaging using interference null space projection.

PURPOSE: In radial abdominal imaging, it has been commonly observed that signal from the arms cause streaks due to system imperfections. We previously introduced a streak removal technique (B-STAR), which is inherently spatially variant and limited to work in image space. In this work, we propose a spatially invariant streak cancellation technique (CACTUS), which can be applied in either image space or k-space and is compatible with iterative reconstructions. THEORY AND METHODS: Streak sources are typically spatially localized and can be represented using a low-dimensional subspace. CACTUS identifies the streak subspace by leveraging the spatial redundancy of receiver coils and projects the data onto the streak null space to eliminate the streaks. When applied in k-space, CACTUS can be combined with iterative reconstructions. CACTUS was tested in phantoms and in vivo abdominal imaging using a radial turbo spin-echo pulse sequence. RESULTS: In phantoms, CACTUS improved T2 estimation in comparison to previous de-streaking methods. In vivo experiments showed that CACTUS reduced streaks and yielded T2 estimation, in regions affected by streaks, closer to a streak-free reference. Evaluation using a clinical abdominal dataset (n = 20) showed that CACTUS is comparable to B-STAR and yields significantly better signal preservation and streak cancellation than coil removal and suppression methods. CONCLUSION: CACTUS provides superior signal preservation and streak reduction performance compared to coil removal and suppression methods. As a clear advantage over B-STAR, CACTUS can be integrated with iterative reconstruction methods. In abdominal T2 mapping, CACTUS improves the accuracy of parameter estimation in areas affected by streaks.

Rapid high-resolution volumetric T1 mapping using a highly accelerated stack-of-stars Look Locker technique.

PURPOSE: To develop a fast volumetric T1 mapping technique. MATERIALS AND METHODS: A stack-of-stars (SOS) Look Locker technique based on the acquisition of undersampled radial data (>30× relative to Nyquist) and an efficient multi-slab excitation scheme is presented. A principal-component based reconstruction is used to reconstruct T1 maps. Computer simulations were performed to determine the best choice of partitions per slab and degree of undersampling. The technique was validated in phantoms against reference T1 values measured with a 2D Cartesian inversion-recovery spin-echo technique. The SOS Look Locker technique was tested in brain (n = 4) and prostate (n = 5). Brain T1 mapping was carried out with and without kz acceleration and results between the two approaches were compared. Prostate T1 mapping was compared to standard techniques. A reproducibility study was conducted in brain and prostate. Statistical analyses were performed using linear regression and Bland Altman analysis. RESULTS: Phantom T1 values showed excellent correlations between SOS Look Locker and the inversion-recovery spin-echo reference (r2 = 0.9965; p < 0.0001) and between SOS Look Locker with slab-selective and non-slab selective inversion pulses (r2 = 0.9999; p < 0.0001). In vivo results showed that full brain T1 mapping (1 mm3) with kz acceleration is achieved in 4 min 21 s. Full prostate T1 mapping (0.9 × 0.9 × 4 mm3) is achieved in 2 min 43 s. T1 values for brain and prostate were in agreement with literature values. A reproducibility study showed coefficients of variation in the range of 0.18-0.2% (brain) and 0.15-0.18% (prostate). CONCLUSION: A rapid volumetric T1 mapping technique was developed. The technique enables high-resolution T1 mapping with adequate anatomical coverage in a clinically acceptable time.

Absolute Configuration Determination of Two Diastereomeric Neovasifuranones A and B from Fusarium oxysporum R1 by a Combination of Mosher's Method and Chiroptical Approach.

Endophytic fungi are one of prolific sources of bioactive natural products with potential application in biomedicine and agriculture. In our continuous search for antimicrobial secondary metabolites from Fusarium oxysporum R1 associated with traditional Chinese medicinal plant Rumex madaio Makino using one strain many compounds (OSMAC) strategy, two diastereomeric polyketides neovasifuranones A (3) and B (4) were obtained from its solid rice medium together with N-(2-phenylethyl)acetamide (1), 1-(3-hydroxy-2-methoxyphenyl)-ethanone (2) and 1,2-seco-trypacidin (5). Their planar structures were unambiguously determined using 1D NMR and MS spectroscopy techniques as well as comparison with the literature data. By a combination of the modified Mosher's reactions and chiroptical methods using time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD) and optical rotatory dispersion (ORD), the absolute configurations of compounds 3 and 4 are firstly confirmed and, respectively, characterized as (4S,7S,8R), (4S,7S,8S). Bioassay results indicate that these metabolites 1-5 exhibit weak inhibitory effect on Helicobacter pylori 159 with MIC values of ≥16 µg/mL. An in-depth discussion for enhancement of fungal metabolite diversity is also proposed in this work.

A residual dense network assisted sparse view reconstruction for breast computed tomography.

To develop and investigate a deep learning approach that uses sparse-view acquisition in dedicated breast computed tomography for radiation dose reduction, we propose a framework that combines 3D sparse-view cone-beam acquisition with a multi-slice residual dense network (MS-RDN) reconstruction. Projection datasets (300 views, full-scan) from 34 women were reconstructed using the FDK algorithm and served as reference. Sparse-view (100 views, full-scan) projection data were reconstructed using the FDK algorithm. The proposed MS-RDN uses the sparse-view and reference FDK reconstructions as input and label, respectively. Our MS-RDN evaluated with respect to fully sampled FDK reference yields superior performance, quantitatively and visually, compared to conventional compressed sensing methods and state-of-the-art deep learning based methods. The proposed deep learning driven framework can potentially enable low dose breast CT imaging.

A multi-scale residual network for accelerated radial MR parameter mapping.

A deep learning MR parameter mapping framework which combines accelerated radial data acquisition with a multi-scale residual network (MS-ResNet) for image reconstruction is proposed. The proposed supervised learning strategy uses input image patches from multi-contrast images with radial undersampling artifacts and target image patches from artifact-free multi-contrast images. Subspace filtering is used during pre-processing to denoise input patches. For each anatomy and relaxation parameter, an individual network is trained. in vivo T1 mapping results are obtained on brain and abdomen datasets and in vivo T2 mapping results are obtained on brain and knee datasets. Quantitative results for the T2 mapping of the knee show that MS-ResNet trained using either fully sampled or undersampled data outperforms conventional model-based compressed sensing methods. This is significant because obtaining fully sampled training data is not possible in many applications. in vivo brain and abdomen results for T1 mapping and in vivo brain results for T2 mapping demonstrate that MS-ResNet yields contrast-weighted images and parameter maps that are comparable to those achieved by model-based iterative methods while offering two orders of magnitude reduction in reconstruction times. The proposed approach enables recovery of high-quality contrast-weighted images and parameter maps from highly accelerated radial data acquisitions. The rapid image reconstructions enabled by the proposed approach makes it a good candidate for routine clinical use.

Synthesis and antibacterial activity of a series novel 5,7-diisoprenyloxyflavone derivatives

In the present study, a series of novel 5,7-diisoprenyloxyflavone derivatives were designed, synthesized, and evaluated for their antibacterial activity. Most of these compounds displayed significant antibacterial effects against Gram-positive bacteria, especially against strains of multidrug-resistant clinical isolates. Compounds 4c, 4g, 4i, 4j, 4k, 4l, 4n, 4q and 4t showed high levels of antimicrobial activity against Staphylococcus aureus RN4220 with minimum inhibitory concentrations of 4.0-20 µM. Compound 4k showed the most potent activity among these compounds against all multidrug-resistant clinical isolates tested. Unfortunately, none of the compounds were active against Gram-negative bacteria at the doses of 24-164 µM.

Syntheses of Benzo[d]Thiazol-2(3H)-One Derivatives and Their Antidepressant and Anticonvulsant Effects.

Thirty-four new benzo[d]thiazol derivatives 2a-2i, 3a-3r, and 4a-4g were synthesized and investigated for their potential antidepressant and anticonvulsant effects. In a forced swimming test, 2c and 2d showed the highest antidepressant and anticonvulsant effects. 2c and 2d displayed a higher percentage decrease in immobility duration (89.96% and 89.62%, respectively) than that of fluoxetine (83.62%). In the maximal electroshock seizure test, 3n and 3q showed the highest anticonvulsant effect, with ED50 values of 46.1 and 64.3 mg kg-1, and protective indices of 6.34 and 4.11, respectively, which were similar to those of phenobarbital or valproate. We also found that the mechanism for the antidepressant activity of 2c and 2d may be via increasing the concentrations of serotonin and norepinephrine.

Chalcone derivatives bearing chromen or benzo[f]chromen moieties: Design, synthesis, and evaluations of anti-inflammatory, analgesic, selective COX-2 inhibitory activities.

Thirty-eight chalconederivatives bearing a chromen or benzo[f]chromen moiety were synthesized and evaluated for their anti-inflammatory and analgesic activities. Using an ear edema model, anti-inflammatory activities were observed for compounds 3a-3s (ear inflammation: 1.75-3.71 mg) and 4a-4s (ear inflammation: 1.71-4.94 mg). All compounds also displayed analgesic effects with inhibition values of 66.7-100% (3a-3s) and 96.2-100% (4a-4s). The 12 compounds that displayed excellent anti-inflammatory and analgesic effects were tested for their inhibitory activity against ovine COX-1 and COX-2. Six compounds bearing a chromen moiety were weak inhibitors of the COX-1 isozyme but showed moderate COX-2 isozyme inhibitory effects (IC50s from 0.37 µM to 0.83 µM) and COX-2 selectivity indexes (SI: 22.49-9.34). Those bearing a benzo[f]chromen moiety were more selective toward COX-2 than those bearing a chromen moiety with IC50s from 0.25 µM to 0.43 µM and COX-2 selectivity indexes from SI: 31.08 to 20.67.

An efficient 3D stack-of-stars turbo spin echo pulse sequence for simultaneous T2-weighted imaging and T2 mapping.

PURPOSE: To design a pulse sequence for efficient 3D T2-weighted imaging and T2 mapping. METHODS: A stack-of-stars turbo spin echo pulse sequence with variable refocusing flip angles and a flexible pseudorandom view ordering is proposed for simultaneous T2-weighted imaging and T2 mapping. An analytical framework is introduced for the selection of refocusing flip angles to maximize relative tissue contrast while minimizing T2 estimation errors and maintaining low specific absorption rate. Images at different echo times are generated using a subspace constrained iterative reconstruction algorithm. T2 maps are obtained by modeling the signal evolution using the extended phase graph model. The technique is evaluated using phantoms and demonstrated in vivo for brain, knee, and carotid imaging. RESULTS: Numerical simulations demonstrate an improved point spread function with the proposed pseudorandom view ordering compared to golden angle view ordering. Phantom experiments show that T2 values estimated from the stack-of-stars turbo spin echo pulse sequence with variable refocusing flip angles have good concordance with spin echo reference values. In vivo results show the proposed pulse sequence can generate qualitatively comparable T2-weighted images as conventional Cartesian 3D SPACE in addition to simultaneously generating 3D T2 maps. CONCLUSION: The proposed stack-of-stars turbo spin echo pulse sequence with pseudorandom view ordering and variable refocusing flip angles allows high resolution isotropic T2 mapping in clinically acceptable scan times. The optimization framework for the selection of refocusing flip angles improves T2 estimation accuracy while generating T2-weighted contrast comparable to conventional Cartesian imaging.

Synthesis, antimicrobial and cytotoxic activities, and molecular docking studies of N-arylsulfonylindoles containing an aminoguanidine, a semicarbazide, and a thiosemicarbazide moiety.

Thirty-six N-arylsulfonyl-3-substituted indoles were designed and synthesized by combining the N-arylsulfonylindoles with aminoguanidine, semicarbazide, and thiosemicarbazide, respectively. Their antibacterial activities were screened, and cytotoxic activities were evaluated. The results showed that aminoguanidines (6) exhibited much better antibacterial activity than semicarbazides (7) and thiosemicarbazides (8). Most compounds in series 6 showed potent inhibitory activity against the tested bacterial strains, including multidrug-resistant strains, with MIC values in the range of 1.08-23.46 µM. The cytotoxic activity of the compounds 6c, 6d, 6h, 6j, 6k and 6l was assessed in two human cancer cell lines A590 and SGC7901, and one human normal cell line HEK 293T. The results indicated that compounds selected exhibited excellent activity against the tested cancer cells with IC50 values in the range of 1.51-15.12 µM suggesting the potential of them as new antibacterial and anticancer agents. What's more, the results of resistance study revealed that resistance of the tested bacteria toward 6d is not easily developed. Molecular docking studies revealed that the aminoguanidine and arylsulfonylindole moieties played a significant role in binding the target site of E. coli FabH-CoA receptor.