Advances in the Development of Bacterial Bioluminescence Imaging.

Bioluminescence imaging (BLI) is a powerful method for visualizing biological processes and tracking cells. Engineered bioluminescent bacteria that utilize luciferase-catalyzed biochemical reactions to generate luminescence have become useful analytical tools for in vitro and in vivo bacterial imaging. Accordingly, this review initially introduces the development of engineered bioluminescent bacteria that use different luciferase-luciferin pairs as analytical tools and their applications for in vivo BLI, including real-time bacterial tracking of infection, probiotic investigation, tumor-targeted therapy, and drug screening. Applications of engineered bioluminescent bacteria as whole-cell biosensors for sensing biological changes in vitro and in vivo are then discussed. Finally, we review the optimizations and future directions of bioluminescent bacteria for imaging. This review aims to provide fundamental insights into bacterial BLI and highlight the potential development of this technique in the future.

Naringenin Inhibits Acid Sphingomyelinase-Mediated Membrane Raft Clustering to Reduce NADPH Oxidase Activation and Vascular Inflammation.

Macrophage inflammation and oxidative stress promote atherosclerosis progression. Naringenin is a naturally occurring flavonoid with antiatherosclerotic properties. Here, we elucidated the effects of naringenin on monocyte/macrophage endothelial infiltration and vascular inflammation. We found naringenin inhibited oxidized low-density lipoprotein (oxLDL)-induced pro-inflammatory cytokines such as IL-1ß, IL-6, and TNF-α toward an M2 macrophage phenotype and inhibited oxLDL-induced TLR4 (Toll-like receptor 4) membrane translocation and downstream NF-κB transcriptional activity. Results from flow cytometric analysis showed that naringenin reduced monocyte/macrophage infiltration in the aorta of high-fat-diet-treated ApoE-deficient mice. The aortic cytokine levels were also inhibited in naringenin-treated mice. Further, we found that naringenin reduced lipid raft clustering and acid sphingomyelinase (ASMase) membrane gathering and inhibited the TLR4 and NADPH oxidase subunit p47phox membrane recruitment, which reduced the inflammatory response. Recombinant ASMase treatment or overexpression of ASMase abolished the naringenin function and activated macrophage and vascular inflammation. We conclude that naringenin inhibits ASMase-mediated lipid raft redox signaling to attenuate macrophage activation and vascular inflammation.

The landscape of super-enhancer regulates remote target gene transcription through loop domains in adipose tissue of pig.

Background: A super-enhancer (SE) is a huge cluster of multiple enhancers that control the key genes for cell identity and function. The rise of advanced chromatin immunoprecipitation sequencing (ChIP-seq) technology such as Cleavage Under Targets and Tagmentation (CUT&Tag) allows more SEs to be discovered. However, SE studies in Luchuan and Duroc pigs are very rare in animal husbandry. Results: We used the CUT&Tag technique to identify 145 and 378 SEs from the adipose tissues of Luchuan and Duroc pigs, respectively. There were significant differences in the peak coverage ratio of SE peaks in the gene promoter region between the two breeds. Not only that, peak signals at the start and end point of the SE peak profile showed obvious spikes. The proximal target genes of SE were highly expressed compared with the background genes and the typical enhancer target genes. Subsequently, in conjoint analysis with high-throughput chromosome conformation capture sequencing (Hi-C seq) data, we predicted the remote regulatory genes of SE and found that their expression level was related to the distance of SE extended to the loop's anchor, but not the length of loops. According to our prediction model, SEs can maintain promoter accessibility of partial remote target genes through loop domains. Finally, a batch of SEs closely related to fat metabolism traits were obtained by performing a coalition analysis of quantitative trait loci and SE data. Conclusions: This work enabled us to obtain hundreds of SEs from Luchuan and Duroc pigs. Our model provides a new method for predicting the SE remote target genes based on loop domains, and to further explore the potential role of super-enhancer in the regulation of fat metabolism.

Deletion of the mitochondrial calcium uniporter in adipose tissue promotes energy expenditure and alleviates diet-induced obesity.

OBJECTIVE: Studies have shown a correlation between obesity and mitochondrial calcium homeostasis, yet it is unclear whether and how Mcu regulates adipocyte lipid deposition. This study aims to provide new potential target for the treatment of obesity and related metabolic diseases, and to explore the function of Mcu in adipose tissue. METHODS: We firstly investigated the role of mitoxantrone, an Mcu inhibitor, in the regulation of glucose and lipid metabolism in mouse adipocytes (3T3-L1 cells). Secondly, C57BL/6J mice were used as a research model to investigate the effects of Mcu inhibitors on fat accumulation and glucose metabolism in mice on a high-fat diet (HFD), and by using CRISPR/Cas9 technology, adipose tissue-specific Mcu knockdown mice (Mcufl/+ AKO) and Mcu knockout of mice (Mcufl/fl AKO) were obtained, to further investigate the direct effects of Mcu on fat deposition, glucose tolerance and insulin sensitivity in mice on a high-fat diet. RESULTS: We found the Mcu inhibitor reduced adipocytes lipid accumulation and adipose tissues mass in mice fed an HFD. Both Mcufl/+ AKO mice and Mcufl/fl AKO mice were resistant to HFD-induced obesity, compared to control mice. Mice with Mcufl/fl AKO showed improved glucose tolerance and insulin sensitivity as well as reduced hepatic lipid accumulation. Mechanistically, inhibition of Mcu promoted mitochondrial biogenesis and adipocyte browning, increase energy expenditure and alleviates diet-induced obesity. CONCLUSIONS: Our study demonstrates a link between adipocyte lipid accumulation and mCa2+ levels, suggesting that adipose-specific Mcu deficiency alleviates HFD-induced obesity and ameliorates metabolic disorders such as insulin resistance and hepatic steatosis. These effects may be achieved by increasing mitochondrial biosynthesis, promoting white fat browning and enhancing energy metabolism.

One-Shot Weakly-Supervised Segmentation in 3D Medical Images.

Deep neural networks typically require accurate and a large number of annotations to achieve outstanding performance in medical image segmentation. One-shot and weakly-supervised learning are promising research directions that reduce labeling effort by learning a new class from only one annotated image and using coarse labels instead, respectively. In this work, we present an innovative framework for 3D medical image segmentation with one-shot and weakly-supervised settings. Firstly a propagation-reconstruction network is proposed to propagate scribbles from one annotated volume to unlabeled 3D images based on the assumption that anatomical patterns in different human bodies are similar. Then a multi-level similarity denoising module is designed to refine the scribbles based on embeddings from anatomical- to pixel-level. After expanding the scribbles to pseudo masks, we observe the miss-classified voxels mainly occur at the border region and propose to extract self-support prototypes for the specific refinement. Based on these weakly-supervised segmentation results, we further train a segmentation model for the new class with the noisy label training strategy. Experiments on three CT and one MRI datasets show the proposed method obtains significant improvement over the state-of-the-art methods and performs robustly even under severe class imbalance and low contrast. Code is publicly available at https://github.com/LWHYC/OneShot_WeaklySeg.

Cobalt-Catalyzed Enantioselective C-H Annulation of Benzylamines with Alkynes: Application to the Modular and Asymmetric Syntheses of Bioactive Molecules.

The transition metal-catalyzed enantioselective C-H functionalization strategy has revolutionized the logic of natural product synthesis. However, previous applications have heavily relied on the use of noble metal catalysts such as rhodium and palladium. Herein, we report the efficient synthesis of C1-chiral 1,2-dihydroisoquinolines (DHIQs) via enantioselective C-H/N-H annulation of picolinamides with alkynes catalyzed by a more sustainable and cheaper 3d metal catalyst, cobalt(II) acetate tetrahydrate. A wide range of enantiomerically enriched DHIQs were obtained in good yields with excellent enantioselectivities (up to 98% yield and >99% ee). The robustness and synthetic potential of this method were demonstrated by the modular and asymmetric syntheses of several tetrahydroisoquinoline alkaloids, including (S)-norlaudanosine, (S)-laudanosine, (S)-xylopinine, (S)-sebiferine, and (S)-cryptostyline II, and the asymmetric syntheses of key intermediates of (+)-solifenacin, FR115427, and (+)-NPS R-568.

An improved gene expression programming algorithm for function mining of map-reduce job execution in catenary monitoring systems.

Gene expression programming (GEP) is one of the most prominent algorithms in function mining. In order to obtain a more accurate function model in configuration parameters-execution efficiency (CP-EE) of map-reduce job in the high-speed railway catenary monitoring system, this paper proposes a novel algorithm, called GEP based on multi-strategy (MS-GEP). Compared to traditional GEP, the proposed algorithm can escape premature convergence and jump out of local optimum. First, an adaptive mutation rate is designed according to the evolutionary generations, population diversity, and individual fitness values. A manual intervention strategy is then proposed to determine whether the algorithm enters the dilemma of local optimum based on the generations of population evolutionary stagnation. Finally, the average quality of the population is changed by randomly replacing individuals, and the ancestral population is traced to change the evolutionary direction. The experimental results on the benchmarks of function mining show that the proposed MS-GEP has better solution quality and higher population diversity than other GEP algorithms. Furthermore, the proposed MS-GEP has higher accuracy on the function model of CP-EE of high-speed railway catenary monitoring system than other commonly used algorithms in the field of function mining.

Arbutin alleviates fatty liver by inhibiting ferroptosis via FTO/SLC7A11 pathway.

Non-alcoholic fatty liver disease (NAFLD) is a potentially serious disease that affects 30 % of the global population and poses a significant risk to human health. However, to date, no safe, effective and appropriate treatment modalities are available. In recent years, ferroptosis has emerged as a significant mode of cell death and has been found to play a key regulatory role in the development of NAFLD. In this study, we found that arbutin (ARB), a natural antioxidant derived from Arctostaphylos uva-ursi (L.), inhibits the onset of ferroptosis and ameliorates high-fat diet-induced NAFLD in vivo and in vitro. Using reverse docking, we identified the demethylase fat mass and obesity-related protein (FTO) as a potential target of ARB. Subsequent mechanistic studies revealed that ARB plays a role in controlling methylation of the SLC7A11 gene through inhibition of FTO. In addition, we demonstrated that SLC7A11 could alleviate the development of NAFLD in vivo and in vitro. Our findings identify the FTO/SLC7A11 axis as a potential therapeutic target for the treatment of NAFLD. Specifically, we show that ARB alleviates NAFLD by acting on the FTO/SLC7A11 pathway to inhibit ferroptosis.

Pd(II)-Catalyzed atroposelective C-H olefination: synthesis of enantioenriched N-aryl peptoid atropisomers.

Herein, we reported the synthesis of enantioenriched N-aryl peptoid atropisomers via Pd(II)-catalyzed atroposelective C-H olefination using the easily accessible L-pyroglutamic acid (L-pGlu-OH) as the chiral ligand. A series of optically active N-aryl peptoid atropisomers were obtained in synthetically useful yields with high enantioselectivities.

Analysis of electromagnetic response of cells and lipid membranes using a model-free method.

Electromagnetic radiation (EMR) is omnipresent on earth and may interact with the biological systems in diverse manners. But the scope and nature of such interactions remain poorly understood. In this study, we have measured the permittivity of cells and lipid membranes over the EMR frequency range of 20 Hz to 4.35 × 1010 Hz. To identify EMR frequencies that display physically intuitive permittivity features, we have developed a model-free method that relies on a potassium chloride reference solution of direct-current (DC) conductivity equal to that of the target sample. The dielectric constant, which reflects the capacity to store energy, displays a characteristic peak at 105-106 Hz. The dielectric loss factor, which represents EMR absorption, is markedly enhanced at 107-109 Hz. The fine characteristic features are influenced by the size and composition of these membraned structures. Mechanical disruption results in abrogation of these characteristic features. Enhanced energy storage at 105-106 Hz and energy absorption at 107-109 Hz may affect certain membrane activity relevant to cellular function.

Textile Bandwidth-Enhanced Polarization-Reconfigurable Half-Mode Substrate-Integrated Cavity Antenna.

A textile bandwidth-enhanced polarization-reconfigurable half-mode substrate-integrated cavity antenna was designed for wearable applications. A slot was cut out from the patch of a basic textile HMSIC antenna to excite two close resonances to form a wide -10 dB impedance band. The simulated axial ratio curve indicates the linear and circular polarization of the antenna radiation at different frequencies. Based on that, two sets of snap buttons were added at the radiation aperture to shift the -10 dB band. Therefore, a larger frequency range can be flexibly covered, and the polarization can be reconfigured at a fixed frequency by switching the state of snap buttons. According to the measured results on a fabricated prototype, the -10 dB impedance band of the proposed antenna can be reconfigured to cover 2.29~2.63 GHz (13.9% fractional bandwidth), and the circular/linear polarization radiation can be observed at 2.42 GHz with buttons OFF/ON. Additionally, simulations and measurements were carried out to validate the design and to study the effects of human body and bending conditions on the antenna performance.

Probing the Effect of Young's Modulus on the Reservoir Regulation Abilities of Dispersed Particle Gels.

The mechanical strength of dispersed particle gels (DPGs), which can be directly characterized by Young's modulus, is an important parameter affecting reservoir regulation performance. However, the effect of reservoir conditions on the mechanical strength of DPGs, as well as the desired range of mechanical strength for optimum reservoir regulation performance, have not been systematically studied. In this paper, DPG particles with different Young's moduli were prepared and their corresponding migration performances, profile control capacities and enhanced oil recovery abilities were studied by simulated core experiments. The results showed that with increase in Young's modulus, the DPG particles exhibited improved performance in profile control as well as enhanced oil recovery. However, only the DPG particles with a modulus range of 0.19-0.762 kPa could achieve both adequate blockage in large pore throats and migration to deep reservoirs through deformation. Considering the material costs, applying DPG particles with moduli within the range of 0.19-0.297 kPa (polymer concentration: 0.25-0.4%; cross-linker concentration: 0.7-0.9%) would ensure optimum reservoir control performance. Direct evidence for the temperature and salt resistance of DPG particles was also obtained. When aged in reservoir conditions below 100 °C and at a salinity of 10 × 104 mg·L-1, the Young's modulus values of the DPG particle systems increased moderately with temperature or salinity, indicating a favorable impact of reservoir conditions on the reservoir regulation abilities of DPG particles. The studies in this paper indicated that the practical reservoir regulation performances of DPGs can be improved by adjusting the mechanical strength, providing basic theoretical guidance for the application of DPGs in efficient oilfield development.

Coelenterazine-Type Bioluminescence-Induced Optical Probes for Sensing and Controlling Biological Processes.

Bioluminescence-based probes have long been used to quantify and visualize biological processes in vitro and in vivo. Over the past years, we have witnessed the trend of bioluminescence-driven optogenetic systems. Typically, bioluminescence emitted from coelenterazine-type luciferin-luciferase reactions activate light-sensitive proteins, which induce downstream events. The development of coelenterazine-type bioluminescence-induced photosensory domain-based probes has been applied in the imaging, sensing, and control of cellular activities, signaling pathways, and synthetic genetic circuits in vitro and in vivo. This strategy can not only shed light on the mechanisms of diseases, but also promote interrelated therapy development. Here, this review provides an overview of these optical probes for sensing and controlling biological processes, highlights their applications and optimizations, and discusses the possible future directions.

Dexmedetomidine postconditioning attenuates myocardial ischemia/reperfusion injury by activating the Nrf2/Sirt3/SOD2 signaling pathway in the rats.

OBJECTIVES: To observe the protective effects of dexmedetomidine (Dex) postconditioning on myocardial ischemia/reperfusion injury (IRI) and to explore its potential molecular mechanisms. METHODS: One-hundred forty-seven male Sprague-Dawley rats were randomly divided into five groups receiving the different treatments: Sham, ischemia/reperfusion (I/R), Dex, Brusatol, Dex + Brusatol. By the in vivo rat model of myocardial IRI, cardioprotective effects of Dex postconditioning were evaluated by assessing serum CK-MB and cTnI levels, myocardial HE and Tunel staining and infarct size. Furthermore, the oxidative stress-related markers including intracellular ROS level, myocardial tissue MDA level, SOD and GSH-PX activities were determined. RESULTS: Dex postconditioning significantly alleviated myocardial IRI, decreased intracellular ROS and myocardial tissue MDA level, increased SOD and GSH-PX activities. Dex postconditioning significantly up-regulated myocardial expression of Bcl-2, down-regulated Bax and cleaved caspase-3 and decreased cardiomyocyte apoptosis rate. furthermores, Dex postconditioning promoted Nrf2 nuclear translocation, increased myocardial expression of Sirt3 and SOD2 and decreased Ac-SOD2. However, brusatol reversed cardioprotective benefits of Dex postconditioning, significantly decreased Dex-induced Nrf2 nuclear translocation and reduced myocardial expression of Sirt3 and SOD2. CONCLUSIONS: Dex postconditioning can alleviate myocardial IRI by suppressing oxidative stress and apoptosis, and these beneficial effects are at least partly mediated by activating the Nrf2/Sirt3/SOD2 signaling pathway.

A high high-density lipoprotein level is associated with Gleason score upgrade in Chinese patients diagnosed with high-grade prostate carcinoma.

BACKGROUND: The high incidence of Gleason score upgrading (GSU) made urologists underestimate the disease, leading to the inaccurate therapeutic decision. The study aimed to explore relevant laboratory examination evidence associated with GSU. METHODS: Patients diagnosed with prostate carcinoma undergoing radical prostatectomy in our center between January 2015 and December 2019 were included in this retrospective study. Patients were divided into GSU and NGSU groups according to the occurrence of GSU. Medical records were reviewed and analyzed between groups. RESULTS: A total of 130 patients were enrolled, including 52 patients diagnosed with GS = 6 (20 NGSU and 32 GSU) and 78 patients with GS = 7 (36 NGSU and 42 GSU). No significant differences in demographic characteristics were found between groups. An increased neutrophil count (OR = 1.326, 95% CI = 1.005-1.748) and a decreased percentage of lymphocytes (OR = 0.951, 95% CI = 0.904-1) were associated with GSU in the GS = 6 group, whereas a high HDL level (OR = 7.735, 95% CI = 0.998-59.957) was associated with GSU in GS = 7 group. Preoperative high neutrophile count and low lymphocyte percentage were correlated with GSU in patients with low-grade prostate cancer. In contrast, high HDL level was associated with GSU in patients with high-grade prostate cancer. CONCLUSIONS: These laboratory examination data could provide urologists with information before making a therapeutic protocol.

Perillartine protects against metabolic associated fatty liver in high-fat diet-induced obese mice.

Metabolic associated fatty liver disease is the main cause of chronic liver disease in the world, but there is still no effective treatment. In the search for drugs to treat liver steatosis, we screened 303 natural products using HepG2 cells and discovered that perillartine derived from Perilla frutescens (L.) improved fat deposition as well as glucose homeostasis in hepatocytes. In vitro, perillartine reduced the expression of genes involved in lipid synthesis, lipid transport, and gluconeogenesis in hepatocytes, increased the number of mitochondria, and upregulated the phosphorylation of Akt. In vivo, perillartine reduced body weight gain and the fat rate, improved glucose metabolism and energy balance, and altered the gut microbial composition in mice given a high-fat diet. In addition, RORγ was identified as a possible target of perillartine through pharmacophore screening. Functional studies revealed that the overexpression of RORγ blocked the effects of perillartine, suggesting that it reduced lipid accumulation and regulated glucose metabolism by inhibiting the transcriptional activity of RORγ. Our results provide new information on a natural product inhibitor for RORγ and reveal that perillartine is a new candidate for the treatment of obesity and metabolic associated fatty liver disease.

Developments in FRET- and BRET-Based Biosensors.

Resonance energy transfer technologies have achieved great success in the field of analysis. Particularly, fluorescence resonance energy transfer (FRET) and bioluminescence resonance energy transfer (BRET) provide strategies to design tools for sensing molecules and monitoring biological processes, which promote the development of biosensors. Here, we provide an overview of recent progress on FRET- and BRET-based biosensors and their roles in biomedicine, environmental applications, and synthetic biology. This review highlights FRET- and BRET-based biosensors and gives examples of their applications with their design strategies. The limitations of their applications and the future directions of their development are also discussed.

Fast multiple graphs learning for multi-view clustering.

Graph-based multi-view clustering has become an active topic due to the efficiency in characterizing both the complex structure and relationship between multimedia data. However, existing methods have the following shortcomings: (1) They are inefficient or even fail for graph learning in large scale due to the graph construction and eigen-decomposition. (2) They cannot well exploit both the complementary information and spatial structure embedded in graphs of different views. To well exploit complementary information and tackle the scalability issue plaguing graph-based multi-view clustering, we propose an efficient multiple graph learning model via a small number of anchor points and tensor Schatten p-norm minimization. Specifically, we construct a hidden and tractable large graph by anchor graph for each view and well exploit complementary information embedded in anchor graphs of different views by tensor Schatten p-norm regularizer. Finally, we develop an efficient algorithm, which scales linearly with the data size, to solve our proposed model. Extensive experimental results on several datasets indicate that our proposed method outperforms some state-of-the-art multi-view clustering algorithms.