Multi-scale Transformer Network with Edge-aware Pre-training for Cross-Modality MR Image Synthesis

Cross-modality magnetic resonance (MR) image synthesis can be used to generate missing modalities from given ones. Existing (supervised learning) methods often require a large number of paired multi-modal data to train an effective synthesis model. However, it is often challenging to obtain sufficient paired data for supervised training. In reality, we often have a small number of paired data while a large number of unpaired data. To take advantage of both paired and unpaired data, in this paper, we propose a Multi-scale Transformer Network (MT-Net) with edge-aware pre-training for cross-modality MR image synthesis. Specifically, an Edge-preserving Masked AutoEncoder (Edge-MAE) is first pre-trained in a self-supervised manner to simultaneously perform 1) image imputation for randomly masked patches in each image and 2) whole edge map estimation, which effectively learns both contextual and structural information. Besides, a novel patch-wise loss is proposed to enhance the performance of Edge-MAE by treating different masked patches differently according to the difficulties of their respective imputations. Based on this proposed pre-training, in the subsequent fine-tuning stage, a Dual-scale Selective Fusion (DSF) module is designed (in our MT-Net) to synthesize missing-modality images by integrating multi-scale features extracted from the encoder of the pre-trained Edge-MAE. Further, this pre-trained encoder is also employed to extract high-level features from the synthesized image and corresponding ground-truth image, which are required to be similar (consistent) in the training. Experimental results show that our MT-Net achieves comparable performance to the competing methods even using $70\%$ of all available paired data. Our code will be publicly available at https://github.com/lyhkevin/MT-Net.Comment: 13 pages, 15 figure

Uncommon fatty acids and cardiometabolic health

Cardiovascular disease (CVD) is a major cause of mortality. The effects of several unsaturated fatty acids on cardiometabolic health, such as eicosapentaenoic acid (EPA) docosahexaenoic acid (DHA), α linolenic acid (ALA), linoleic acid (LA), and oleic acid (OA) have received much attention in past years. In addition, results from recent studies revealed that several other uncommon fatty acids (fatty acids present at a low content or else not contained in usual foods), such as furan fatty acids, n-3 docosapentaenoic acid (DPA), and conjugated fatty acids, also have favorable effects on cardiometabolic health. In the present report, we searched the literature in PubMed, Embase, and the Cochrane Library to review the research progress on anti-CVD effect of these uncommon fatty acids. DPA has a favorable effect on cardiometabolic health in a different way to other long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs), such as EPA and DHA. Furan fatty acids and conjugated linolenic acid (CLNA) may be potential bioactive fatty acids beneficial for cardiometabolic health, but evidence from intervention studies in humans is still limited, and well-designed clinical trials are required. The favorable effects of conjugated linoleic acid (CLA) on cardiometabolic health observed in animal or in vitro cannot be replicated in humans. However, most intervention studies in humans concerning CLA have only evaluated its effect on cardiometabolic risk factors but not its direct effect on risk of CVD, and randomized controlled trials (RCTs) will be required to clarify this point. However, several difficulties and limitations exist for conducting RCTs to evaluate the effect of these fatty acids on cardiometabolic health, especially the high costs for purifying the fatty acids from natural sources. This review provides a basis for better nutritional prevention and therapy of CVD

Nonparaxiality-triggered Landau-Zener transition in topological photonic waveguides

Photonic lattices have been widely used for simulating quantum physics, owing to the similar evolutions of paraxial waves and quantum particles. However, nonparaxial wave propagations in photonic lattices break the paradigm of the quantum-optical analogy. Here, we reveal that nonparaxiality exerts stretched and compressed forces on the energy spectrum in the celebrated Aubry-Andre-Harper model. By exploring the mini-gaps induced by the finite size of the different effects of nonparaxiality, we experimentally present that the expansion of one band gap supports the adiabatic transfer of boundary states while Landau-Zener transition occurs at the narrowing of the other gap, whereas identical transport behaviors are expected for the two gaps under paraxial approximation. Our results not only serve as a foundation of future studies of dynamic state transfer but also inspire applications leveraging nonparaxial transitions as a new degree of freedom.Comment: 17 pages, 4 figure

Dual protective role of velutin against articular cartilage degeneration and subchondral bone loss via the p38 signaling pathway in murine osteoarthritis

Osteoarthritis (OA) is a common degenerative joint condition associated with inflammation and characterized by progressive degradation of the articular cartilage and subchondral bone loss in the early stages. Inflammation is closely associated with these two major pathophysiological changes in OA. Velutin, a flavonoid family member, reportedly exerts anti-inflammatory effects. However, the therapeutic effects of velutin in OA have not yet been characterized. In this study, we explore the effects of velutin in an OA mouse model. Histological staining and micro-CT revealed that velutin had a protective effect against cartilage degradation and subchondral bone loss in an OA mouse model generated by surgical destabilization of the medial meniscus (DMM). Additionally, velutin rescued IL-1β-induced inflammation in chondrocytes and inhibited RANKL-induced osteoclast formation and bone resorption in vitro. Mechanistically, the p38 signaling pathway was found to be implicated in the inhibitory effects of velutin. Our study reveals the dual protective effects of velutin against cartilage degradation and subchondral bone loss by inhibiting the p38 signaling pathway, thereby highlighting velutin as an alternative treatment for OA

Effect of vitamin B 12 and n-3 polyunsaturated fatty acids on plasma homocysteine, ferritin, C-reaction protein, and other cardiovascular risk factors: a randomized controlled trial

Objectives: Vitamin B 12 and n-3 polyunsaturated fatty acids (PUFA) decrease blood homocysteine (Hcy) concentrations. However, the combined effect of these nutrients on Hcy and ferritin, and C-reactive protein is limited and inconclusive. The objective was to examine the synergistic effect of vitamin B 12 in combination of n-3 PUFA on plasma Hcy, ferritin, and other biochemical markers. Methods: In a randomized controlled trial, thirty eligible subjects were randomly divided into three groups, and assigned to receive 1000 μg of vitamin B 12 , 2 g fish oil, or 1000 μg vitamin B 12 and 2 g fish oil, respectively, for 8 weeks. Plasma phospholipids (PL) fatty acids and biochemical markers were determined. This study was registered under ClinicalTrials.gov Identifier: NCT01762072. Results: Plasma PL 20:5n-3, 22:6n-3 and n-3 PUFA was increased after 4 and 8 week supplementation of fish oil, and vitamin B 12 +fish oil. Plasma concentrations of triacylglycerol, uric acid, C-reactive protein, and ferritin were significantly decreased after 4 and 8 week supplementation of fish oil, and vitamin B 12 +fish oil. In all groups, significant changes in plasma Hcy were observed during the study period. Vitamin B 12 , fish oil, and vitamin B 12 +fish oil supplementation lowered plasma Hcy concentrations by 22%, 19%, and 39%, respectively. Conclusions: The combination of vitamin B 12 and fish oil has a synergistic effect on lowering plasma concentrations of Hcy

Replication of a Gene-Diet Interaction at CD36, NOS3 and PPARG in Response to Omega-3 Fatty Acid Supplements on Blood Lipids: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Modulation of genetic variants on the effect of omega-3 fatty acid supplements on blood lipids is still unclear. METHODS: In a double-blind randomized controlled trial, 150 patients with type 2 diabetes (T2D) were randomized into omega-3 fatty acid group (n = 56 for fish oil and 44 for flaxseed oil) and control group (n = 50) for 180 days. All patients were genotyped for genetic variants at CD36 (rs1527483), NOS3 (rs1799983) and PPARG (rs1801282). Linear regression was used to examine the interaction between omega-3 fatty acid intervention and CD36, NOS3 or PPARG variants for blood lipids. FINDINGS: Significant interaction with omega-3 fatty acid supplements was observed for CD36 on triglycerides (p-interaction = 0.042) and PPAGR on low-density lipoprotein-cholesterol (p-interaction = 0.02). We also found a significant interaction between change in erythrocyte phospholipid omega-3 fatty acid composition and NOS3 genotype on triglycerides (p-interaction = 0.042), total cholesterol (p-interaction = 0.013) and ratio of total cholesterol to high-density lipoprotein cholesterol (p-interaction = 0.015). The T2D patients of CD36-G allele, PPARG-G allele and NOS3-A allele tended to respond better to omega-3 fatty acids in improving lipid profiles. The interaction results of the omega-3 fatty acid group were mainly attributed to the fish oil supplements. INTERPRETATION: This study suggests that T2D patients with different genotypes at CD36, NOS3 and PPARG respond differentially to intervention of omega-3 supplements in blood lipid profiles

Coexistence of Microbial Species in Structured Communities by Forming a Hawk-Dove Game Like Interactive Relationship

Microorganisms evolve kinds of elaborate interaction models that can form relatively stable communities in a wide range of ecosystems. It is recognized that the spatial genetic structure of microbes in surface-attached environments lays a good foundation for the persistence of polymicrobial communities in adverse conditions. However, the interacting dynamics of microbes in facilitating the formation and stabilization of community structure still remains elusive. In this study, we identify a hawk-dove game like interspecific relationship between the two Gram-negative opportunistic pathogens Pseudomonas aeruginosa and Klebsiella pneumoniae, which naturally coexist in insect gut and can cocolonize human tissues. Specifically, although P. aeruginosa had significant competitive advantage over cocultured K. pneumoniae on solid medium with rich nutrient factors, K. pneumoniae could resist the suppression of P. aeruginosa by enhancing the expression of membrane transporters induced by the extracellular metabolites of P. aeruginosa. By contrast, under the condition that K. pneumoniae had a growth advantage but P. aeruginosa met a metabolic burden in producing quorum-sensing-controlled extracellular products, the frequency of K. pneumoniae would be slightly higher than P. aeruginosa during the coexistence because K. pneumoniae was also capable of exploiting the extracellular metabolite from P. aeruginosa. In addition, P. aeruginosa quorum-sensing variant could reap benefits from K. pneumoniae in turn and reach a relatively stable two species equilibrium. These findings provide an explanation for the formation and maintenance of polymicrobial communities in different spatially structured environments, and thus may contribute to understanding the complex interspecific interactions of microbes in local communities and shed new light on the development of social microbiology

The C-Terminal Effector Domain of Non-Structural Protein 1 of Influenza A Virus Blocks IFN-β Production by Targeting TNF Receptor-Associated Factor 3

Influenza A virus non-structural protein 1 (NS1) antagonizes interferon response through diverse strategies, particularly by inhibiting the activation of interferon regulatory factor 3 (IRF3) and IFN-β transcription. However, the underlying mechanisms used by the NS1 C-terminal effector domain (ED) to inhibit the activation of IFN-β pathway are not well understood. In this study, we used influenza virus subtype of H5N1 to demonstrate that the NS1 C-terminal ED but not the N-terminal RNA-binding domain, binds TNF receptor-associated factor 3 (TRAF3). This results in an attenuation of the type I IFN signaling pathway. We found that the NS1 C-terminal ED (named NS1/126-225) inhibits the active caspase activation and recruitment domain-containing form of RIG-I [RIG-I(N)]-induced IFN-β reporter activity, the phosphorylation of IRF3, and the induction of IFN-β. Further analysis showed that NS1/126-225 binds to TRAF3 through the TRAF domain, subsequently decreasing TRAF3 K63-linked ubiquitination. NS1/126-225 binding also disrupted the formation of the mitochondrial antiviral signaling (MAVS)–TRAF3 complex, increasing the recruitment of IKKε to MAVS; ultimately shutting down the RIG-I(N)-mediated signal transduction and cellular antiviral responses. This attenuation of cellular antiviral responses leads to evasion of the innate immune response. Taken together, our findings offer an important insight into the interplay between the influenza virus and host innate immunity