Synthesis of Phenylboronic Acid-Functionalized Magnetic Nanoparticles for Sensitive Soil Enzyme Assays.

Soil enzymes, such as invertase, urease, acidic phosphatase and catalase, play critical roles in soil biochemical reactions and are involved in soil fertility. However, it remains a great challenge to efficiently concentrate soil enzymes and sensitively assess enzyme activity. In this study, we synthesized phenylboronic acid-functionalized magnetic nanoparticles to rapidly capture soil enzymes for sensitive soil enzyme assays. The iron oxide magnetic nanoparticles (MNPs) were firstly prepared by the co-precipitation method and then functionalized by (3-aminopropyl)triethoxysilane, polyethyleneimine and phenylboric acid in turn, obtaining the final nanoparticles (MNPPBA). Protein-capturing assays showed that the functionalized MNPs had a much higher protein-capturing capacity than the naked MNPs (56% versus 6%). Moreover, MNPPBA almost thoroughly captured the tested enzymes, i.e., urease, invertase, and alkaline phosphatase, from enzyme solutions. Based on MNPPBA, a soil enzyme assay method was developed by integration of enzyme capture, magnetic separation and trace enzyme analysis. The method was successfully applied in determining trace enzyme activity in rhizosphere soil. This study provides a strategy to sensitively determine soil enzyme activity for mechanistic investigation of soil fertility and plant-microbiome interaction.

Super enhancers at the miR-146a and miR-155 genes contribute to self-regulation of inflammation.

Inflammatory response is essential to host defense and repair, and requires tight regulation as excessive and constant inflammatory response is deleterious. We recently identified that one of the general but key mechanisms for inflammatory gene transcription regulation is controlled by the formation of super enhancers mediated by NF-κB, and bromodomain and extraterminal (BET) proteins. Given that microRNA transcription shares a similar mechanism to mRNA, we assume that the inflammatory microRNAs transcription could be NF-κB and BET bromodomain dependent. In the present study, we confirmed that inflammatory stimuli changed human umbilical vein endothelial cells (HUVEC) microRNA profile. Among these microRNAs, miR-146a and miR-155, two well-established inflammatory microRNAs, are both downregulated at transcriptional level by NF-κB and BET bromodomain inhibition. To pursue this mechanism, we analyzed the ChIP-seq data and found that NF-κB, BRD4 and RNA POL II were rapidly distributed at the upstream regions of miR-146a and miR-155, and more importantly mediated the formation of the super enhancers that drive miR-146a and miR-155 transcription. These microRNAs transcription driven by super enhancers in turn downregulate both in vitro and in vivo canonical inflammatory genes expression through targeting inflammatory mediators. This novel finding demonstrated how the host self-regulates inflammatory genes expression at both transcriptional and post-transcriptional level to ensure the appropriate level of the host inflammatory response.

BET bromodomain is a novel regulator of TAZ and its activity.

Transcriptional coactivator with PDZ-binding motif (TAZ) is a key transcriptional mediator of Hippo signaling that has been recently reported to mediate Wnt-activated transcription and serve as a component to suppress canonical Wnt/ß-catenin activity. The Bromodomain and Extra-terminal domain (BET) family of proteins can recognize the acetylated lysine chain on histones and plays a critical role in transcriptional regulation. However, the mechanisms underlying transcriptional repression by the BET bromodomain are poorly understood. Here, we found that BET bromodomain inhibition upregulated TAZ protein and its transcriptional output, independent of its well-established role as a mediator of Hippo and Wnt signaling. Additionally, JQ1, a synthetic BET inhibitor, suppressed Wnt/ß-catenin activity by upregulating TAZ. Although JQ1 upregulated TAZ, which is known to promote cell proliferation, it drastically suppressed the growth of colon cancer cells by inducing cell cycle arrest. Collectively, our study identified an unexpected transcriptional repression function of the BET bromodomain and a novel mechanism for TAZ upregulation.

Tongue crack recognition using segmentation based deep learning.

Tongue cracks refer to fissures with different depth and shapes on the tongue's surface, which can characterize the pathological characteristics of spleen and stomach. Tongue cracks are of great significance to the objective study of tongue diagnosis. However, tongue cracks are small and complex, existing methods are difficult to extract them effectively. In order to achieve more accurate extraction and identification of tongue crack, this paper proposes to apply a deep learning network based on image segmentation (Segmentation-Based Deep-Learning, SBDL) to extract and identify tongue crack. In addition, we have studied the quantitative description of tongue crack features. Firstly, the pre-processed tongue crack samples were amplified by using adding salt and pepper noise, changing the contrast and horizontal mirroring; secondly, the annotation tool Crack-Tongue was used to label tongue crack; thirdly, the tongue crack extraction model was trained by using SBDL; fourthly, the cracks on the tongue surface were detected and located by the segmentation network, and then the output and features of the segmentation network were put into the decision network for the classification of crack tongue images; finally, the tongue crack segmentation and identification results were quantitatively evaluated. The experimental results showed that the tongue crack extraction and recognition results based on SBDL were better than Mask Region-based Convolutional Neural Network (Mask R-CNN), DeeplabV3+, U-Net, UNet++ and Semantic Segmentation with Adversarial Learning (SegAN). This method effectively solved the inaccurate tongue crack extraction caused by the tongue crack's color being close to the surrounding tongue coating's color. This method can achieve better tongue crack extraction and recognition results on a small tongue crack data set and provides a new idea for tongue crack recognition, which is of practical value for tongue diagnosis objectification.

Spectral efficiency limits of pre-filtered modulation formats.

We investigate the spectral efficiency (SE) limit of pre-filtered modulation in optical fiber communication systems. We show that pre-filtering induced symbol correlation generates a modulation with memory and, thus, a higher SE limit than that of the original memoryless modulation. The SE limits of a series of modulation formats with varying number L of correlated symbols producing 50% of the original bandwidth are evaluated, which approach the SE limit of a modulation format with 50% pre-filtering as L --> ∞. We show that the SE limit of a modulation format with L correlated symbols approximates a lower bound for the SE limit of the corresponding pre-filtered format.

Population based and animal study on the effects of Schistosoma japonicum infection in the regulation of host glucose homeostasis.

Although parasitic infection affects the glucose homeostasis of mice, only few studies have integrated epidemiological and animal data to determine the effect of Schistosoma japonicum infection on mice metabolism. The current study assessed the effects of S. japonicum infection on blood glucose and other metabolic parameters in both patients and animal models of chronic schistomiasis. A total of 2183 patients with chronic schistosomiasis and age- and gender-matched individuals without schistosomiasis (n = 1798) were enrolled in this study. Fasting blood glucose and other metabolic parameters, including body mass index (BMI) and serum triglyceride and total cholesterol, were compared between the two groups. Mice infected with S. japonicum were used to test the effects of the parasite on glucose tolerance. We found that chronic schistosomiasis patients had significantly lower BMI and fasting blood glucose, serum triglyceride, and total cholesterol levels than non-schistosomiasis individuals. In the animal studies, both bisexual and unisexual S. japonicum infection improved glucose tolerance in wild-type mice. Additionally, S. japonicum-infected ob/ob mice, a model that spontaneously develops obesity and diabetes, also had decreased body weight and improved glucose tolerance. We further observed that S. japonicum-infected mice had lower inflammatory gene expression in the visceral white adipose tissue than the control mice. Collectively, our results demonstrated that S. japonicum infection improved glucose tolerance and other metabolic parameters both in human and animals. Downregulated inflammatory gene expression due to S. japonicum infection might be among the mechanisms for the improved glucose tolerance.

Extensive metabolic disorders are present in APC(min) tumorigenesis mice.

Wnt signaling plays essential role in mesenchymal stem cell (MSC) differentiation. Activation of Wnt signaling suppresses adipogenesis, but promotes osteogenesis in MSC. Adenomatous polyposis coli (APC) is a negative regulator of ß-catenin and Wnt signaling activity. The mutation of APC gene leads to the activation of Wnt signaling and is responsible for tumorigenesis in APC(min) mouse; however, very few studies focused on its metabolic abnormalities. The present study reports a widespread metabolic disorder phenotype in APC(min) mice. The old APC(min) mice have decreased body weight and impaired adipogenesis, but severe hyperlipidemia, which mimic the phenotypes of Familial Adenomatous Polyposis (FAP), an inherited disease also caused by APC gene mutation in human. We found that the expression of lipid metabolism and free fat acids (FA) use genes in the white adipose tissue (WAT) of the APC(min) mice is much lower than those of control. The changed gene expression pattern may lead to the disability of circulatory lipid transportation and storage at WAT. Moreover, the APC(min) mice could not maintain the core body temperature in cold condition. PET-CT determination revealed that the BAT of APC(min) mice has significantly impaired ability to take up (18)FDG from the blood. Morphological studies identified that the brown adipocytes of APC(min) mice were filled with lipid droplets but fewer mitochondria. These results matched with the findings of impaired BAT function in APC(min) mice. Collectively, our study explores a new mechanism that explains abnormal metabolism in APC(min) mice and provides insights into studying the metabolic disorders of FAP patients.