Purpose
Interests have been rapidly growing in the field of radiotherapy to replace CT with magnetic resonance imaging (MRI), due to superior soft tissue contrast offered by MRI and the desire to ...reduce unnecessary radiation dose. MR‐only radiotherapy also simplifies clinical workflow and avoids uncertainties in aligning MR with CT. Methods, however, are needed to derive CT‐equivalent representations, often known as synthetic CT (sCT), from patient MR images for dose calculation and DRR‐based patient positioning. Synthetic CT estimation is also important for PET attenuation correction in hybrid PET‐MR systems. We propose in this work a novel deep convolutional neural network (DCNN) method for sCT generation and evaluate its performance on a set of brain tumor patient images.
Methods
The proposed method builds upon recent developments of deep learning and convolutional neural networks in the computer vision literature. The proposed DCNN model has 27 convolutional layers interleaved with pooling and unpooling layers and 35 million free parameters, which can be trained to learn a direct end‐to‐end mapping from MR images to their corresponding CTs. Training such a large model on our limited data is made possible through the principle of transfer learning and by initializing model weights from a pretrained model. Eighteen brain tumor patients with both CT and T1‐weighted MR images are used as experimental data and a sixfold cross‐validation study is performed. Each sCT generated is compared against the real CT image of the same patient on a voxel‐by‐voxel basis. Comparison is also made with respect to an atlas‐based approach that involves deformable atlas registration and patch‐based atlas fusion.
Results
The proposed DCNN method produced a mean absolute error (MAE) below 85 HU for 13 of the 18 test subjects. The overall average MAE was 84.8 ± 17.3 HU for all subjects, which was found to be significantly better than the average MAE of 94.5 ± 17.8 HU for the atlas‐based method. The DCNN method also provided significantly better accuracy when being evaluated using two other metrics: the mean squared error (188.6 ± 33.7 versus 198.3 ± 33.0) and the Pearson correlation coefficient(0.906 ± 0.03 versus 0.896 ± 0.03). Although training a DCNN model can be slow, training only need be done once. Applying a trained model to generate a complete sCT volume for each new patient MR image only took 9 s, which was much faster than the atlas‐based approach.
Conclusions
A DCNN model method was developed, and shown to be able to produce highly accurate sCT estimations from conventional, single‐sequence MR images in near real time. Quantitative results also showed that the proposed method competed favorably with an atlas‐based method, in terms of both accuracy and computation speed at test time. Further validation on dose computation accuracy and on a larger patient cohort is warranted. Extensions of the method are also possible to further improve accuracy or to handle multi‐sequence MR images.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Full text
Available for:
CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
3.
Supramolecular chiroptical switches Zhang, Li; Wang, Han-Xiao; Li, Shuai ...
Chemical Society reviews,
12/2020, Volume:
49, Issue:
24
Journal Article
Peer reviewed
Chiroptical switches, whose chiral optical signals such as optical rotatory dispersion (ORD), circular dichroism (CD) and circularly polarized luminescence (CPL) are reversibly interchangeable ...between two states, offer many promising applications in the fields of chiral sensing, optical displays, information storage, asymmetric catalysis and so on. Through various non-covalent interactions, supramolecular chiroptical switches have been constructed by combining the chiral and responsive functional components. This review summarizes the recent progress in the construction of supramolecular chiroptical switchable systems that reversibly respond to various stimuli, such as light, electricity, magnetic fields, mechanical force, solvents, pH, temperature, and chemical additives. The switching of supramolecular chirality in the forms of on/off, amplification/weakening and chirality inversion is shown. Additionally, the design of chiroptical switchable systems for chiral logic gates, data communication, chiral separation and asymmetric catalysis has been demonstrated. Future challenges in developing supramolecular chiroptical switches are also discussed.
Recent progress in chiroptical switches including on/off, amplification, and inversion of the chiral signals such as ECD and CPL in supramolecular assemblies is shown.
The visionary idea that RNA adopts nonbiological roles in today's nanomaterial world has been nothing short of phenomenal. These RNA molecules have ample chemical functionality and self‐assemble to ...form distinct nanostructures in response to external stimuli. They may be combined with inorganic materials to produce nanomachines that carry cargo to a target site in a controlled manner and respond dynamically to environmental changes. Comparable to biological cells, programmed RNA nanomachines have the potential to replicate bone healing in vitro. Here, an RNA–biomineral nanomachine is developed, which accomplishes intrafibrillar and extrafibrillar mineralization of collagen scaffolds to mimic bone formation in vitro. Molecular dynamics simulation indicates that noncovalent hydrogen bonding provides the energy source that initiates self‐assembly of these nanomachines. Incorporation of the RNA–biomineral nanomachines into collagen scaffolds in vivo creates an osteoinductive microenvironment within a bone defect that is conducive to rapid biomineralization and osteogenesis. Addition of RNA‐degrading enzymes into RNA–biomineral nanomachines further creates a stop signal that inhibits unwarranted bone formation in tissues. The potential of RNA in building functional nanostructures has been underestimated in the past. The concept of RNA–biomineral nanomachines participating in physiological processes may transform the nanoscopic world of life science.
An RNA–amorphous calcium phosphate nanomachine that induces extrafibrillar and intrafibrillar mineralization of collagen fibrils and regenerates new bone in a dynamic and programmable manner is developed. This multifunctional nanomachinery is comparable to the function of osteoblasts. The RNA–biomineral nanomachines that simulate physiological processes brings new opportunities and challenges to bone tissue engineering.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
An enhancement strategy is realized for ultralong bright room‐temperature phosphorescence (RTP), involving polymerization between phosphor monomers and acrylamide and host–guest complexation ...interaction between phosphors and cucurbit6,7,8urils (CB6,7,8). The non‐phosphorescent monomers exhibit 2.46 s ultralong lifetime after copolymerizing with acrylamide. The improvement is due to the rich hydrogen bond and carbonyl within the polymers which promote intersystem crossing, suppress nonradiative relaxation and shield quenchers effectively. By tuning the ratio of chromophores, a series of phosphorescent copolymers with different lifetimes and quantum yields are prepared. The complexation of macrocyclic hosts CB6,7,8 promote the RTP of polymers by blocking aggregation‐caused quenching, and offsetting the losses of aforementioned interaction provided by polymer. Multiple lifetime‐encoding for digit and character encryption are achieved by utilizing the difference of their lifetimes.
A synergistic enhancement strategy is realized for ultralong bright RTP, involving polymerization between phosphor monomers and acrylamide and host–guest complexation interaction between phosphors and cucurbit6, 7, 8urils (CB6, 7, 8). The phosphorescence lifetime and efficiency is up to 2.81 s and 76 %. Multiple lifetime‐encoding for digit and character encryption are achieved.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The overall response of cisplatin-based chemotherapy in bladder urothelial carcinoma (BUC) remains unsatisfactory due to the complex pathological subtypes, genomic difference, and drug resistance. ...The genes that associated with cisplatin resistance remain unclear. Herein, we aimed to identify the cisplatin resistance associated genes in BUC. EXPERIMENTAL DESIGN: The cytotoxicity of cisplatin was evaluated in six bladder cancer cell lines to compare their responses to cisplatin. The T24 cancer cells exhibited the lowest sensitivity to cisplatin and was therefore selected to explore the mechanisms of drug resistance. We performed genome-wide CRISPR screening in T24 cancer cells in vitro, and identified that the gene heterogeneous nuclear ribonucleoprotein U (HNRNPU) was the top candidate gene related to cisplatin resistance. Epigenetic and transcriptional profiles of HNRNPU-depleted cells after cisplatin treatment were analyzed to investigate the relationship between HNRNPU and cisplatin resistance. In vivo experiments were also performed to demonstrate the function of HNRNPU depletion in cisplatin sensitivity.
Significant correlation was found between HNRNPU expression level and sensitivity to cisplatin in bladder cancer cell lines. In the high HNRNPU expressing T24 cancer cells, knockout of HNRNPU inhibited cell proliferation, invasion, and migration. In addition, loss of HNRNPU promoted apoptosis and S-phase arrest in the T24 cells treated with cisplatin. Data from The Cancer Genome Atlas (TCGA) demonstrated that HNRNPU expression was significantly higher in tumor tissues than in normal tissues. High HNRNPU level was negatively correlated with patient survival. Transcriptomic profiling analysis showed that knockout of HNRNPU enhanced cisplatin sensitivity by regulating DNA damage repair genes. Furthermore, it was found that HNRNPU regulates chemosensitivity by affecting the expression of neurofibromin 1 (NF1).
Our study demonstrated that HNRNPU expression is associated with cisplatin sensitivity in bladder urothelial carcinoma cells. Inhibition of HNRNPU could be a potential therapy for cisplatin-resistant bladder cancer.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Macrocyclic arenes including calixarenes, resorcinarenes, cyclotriveratrylene, pillararenes and so on have emerged as highly attractive synthetic macrocyclic hosts due to their unique structures, ...facile functionalization, and broad range of applications. In recent years, there has been growing interest in the development of novel macrocyclic arenes composed of various aromatic building blocks bridged by methylene groups, which have found applications in various research areas. Consequently, the development of novel macrocyclic arenes has become a frontier and hot topic in supramolecular and macrocyclic chemistry. In this review, we feature the recent advances in the synthesis and applications of novel macrocyclic arenes that have emerged in the last decade. The general synthetic strategies employed for these macrocyclic arenes are systematically summarized, and their wide applications in molecular recognition and assemblies, molecular machines, biomedical science and functional materials are highlighted.
In this review, we summarize the recent advances in newly reported macrocyclic arenes, focusing on their synthetic strategies and applications.
Objective
Changes in gut microbiota have been linked to systemic lupus erythematosus (SLE), but knowledge is limited. Our study aimed to provide an in‐depth understanding of the contribution of gut ...microbiota to the immunopathogenesis of SLE.
Methods
Fecal metagenomes from 117 patients with untreated SLE and 52 SLE patients posttreatment were aligned with 115 matched healthy controls and analyzed by whole‐genome profiling. For comparison, we assessed the fecal metagenome of MRL/lpr mice. The oral microbiota origin of the gut species that existed in SLE patients was documented by single‐nucleotide polymorphism–based strain‐level analyses. Functional validation assays were performed to demonstrate the molecular mimicry of newly found microbial peptides.
Results
Gut microbiota from individuals with SLE displayed significant differences in microbial composition and function compared to healthy controls. Certain species, including the Clostridium species ATCC BAA‐442 as well as Atopobium rimae, Shuttleworthia satelles, Actinomyces massiliensis, Bacteroides fragilis, and Clostridium leptum, were enriched in SLE gut microbiota and reduced after treatment. Enhanced lipopolysaccharide biosynthesis aligned with reduced branched chain amino acid biosynthesis was observed in the gut of SLE patients. The findings in mice were consistent with our findings in human subjects. Interestingly, some species with an oral microbiota origin were enriched in the gut of SLE patients. Functional validation assays demonstrated the proinflammatory capacities of some microbial peptides derived from SLE‐enriched species.
Conclusion
This study provides detailed information on the microbiota of untreated patients with SLE, including their functional signatures, similarities with murine counterparts, oral origin, and the definition of autoantigen‐mimicking peptides. Our data demonstrate that microbiome‐altering approaches may offer valuable adjuvant therapies in SLE.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
After 45 years of its first observation, surface-enhanced Raman spectroscopy (SERS) has become an ultrasensitive tool applied in chemical analysis, materials science, and biomedical research. ...SERS-active nanomaterials, such as noble metals, transition metals, and semiconductors, have undergone extensive development. The hybridization of semiconductors with plasmonic metal nanomaterials is highly effective in boosting light harvesting and conversion, which enables the rapid growth of metal-semiconductor hybrid nanostructures in SERS-based research fields. With the combination of the unique photoelectric properties and giant SERS signals attributed to the synergistic contribution of plasmons and change transfer (CT), metal-semiconductor heterostructures allow diverse and novel applications of SERS in CT investigations for the rational design of photovoltaic devices and ultrasensitive chemical or biological sensing. In this review, we specifically discuss SERS-active metal-semiconductor heterostructures including their building blocks, enhancement mechanisms, and applications. Moreover, we highlight the current challenges and opportunities for future research in this field based on our recent studies and other related research.
SERS on metal-semiconductor heterostructures including their building blocks, enhancement mechanisms and applications was reviewed. The synergistic contribution of plasmons and charge transfer is highlighted.
Computed structures of core eukaryotic protein complexes Humphreys, Ian R; Pei, Jimin; Baek, Minkyung ...
Science (American Association for the Advancement of Science),
2021-Dec-10, 2021-12-10, 20211210, Volume:
374, Issue:
6573
Journal Article
Peer reviewed
Open access
Protein-protein interactions play critical roles in biology, but the structures of many eukaryotic protein complexes are unknown, and there are likely many interactions not yet identified. We take ...advantage of advances in proteome-wide amino acid coevolution analysis and deep-learning–based structure modeling to systematically identify and build accurate models of core eukaryotic protein complexes within the
proteome. We use a combination of RoseTTAFold and AlphaFold to screen through paired multiple sequence alignments for 8.3 million pairs of yeast proteins, identify 1505 likely to interact, and build structure models for 106 previously unidentified assemblies and 806 that have not been structurally characterized. These complexes, which have as many as five subunits, play roles in almost all key processes in eukaryotic cells and provide broad insights into biological function.
PDF
