Radiomics in liver diseases: Current progress and future opportunities

Liver diseases, a wide spectrum of pathologies from inflammation to neoplasm, have become an increasingly significant health problem worldwide. Noninvasive imaging plays a critical role in the clinical workflow of liver diseases, but conventional imaging assessment may provide limited information. Accurate detection, characterization and monitoring remain challenging. With progress in quantitative imaging analysis techniques, radiomics emerged as an efficient tool that shows promise to aid in personalized diagnosis and treatment decision‐making. Radiomics could reflect the heterogeneity of liver lesions via extracting high‐throughput and high‐dimensional features from multi‐modality imaging. Machine learning algorithms are then used to construct clinical target‐oriented imaging biomarkers to assist disease management. Here, we review the methodological process in liver disease radiomics studies in a stepwise fashion from data acquisition and curation, region of interest segmentation, liver‐specific feature extraction, to task‐oriented modelling. Furthermore, the applications of radiomics in liver diseases are outlined in aspects of diagnosis and staging, evaluation of liver tumour biological behaviours, and prognosis according to different disease type. Finally, we discuss the current limitations of radiomics in liver disease studies and explore its future opportunities.     

泛素-蛋白酶体系统与呼吸系统疾病

蛋白是细胞功能的主要执行者,蛋白的质量和数量与细胞功能和疾病有着密切的联系。蛋白的降解系统控制着蛋白的数量,泛素一蛋白酶体系统是细胞内蛋白的主要降解系统,负责细胞内大部分蛋白的降解。对于泛素一蛋白酶体与心血管、肿瘤和神经系统的关系目前研究的比较多,一些新的I艋床药物也应运到临床为患者带来福音。而该系统与呼吸系统疾病关系的研究并不多,了解泛素一蛋白酶体系统在呼吸系统疾病中的作用对于呼吸系统疾病的防治有重要的意义。     

Bacterial rheotaxis

The motility of organisms is often directed in response to environmental stimuli. Rheotaxis is the directed movement resulting from fluid velocity gradients, long studied in fish, aquatic invertebrates, and spermatozoa. Using carefully controlled microfluidic flows, we show that rheotaxis also occurs in bacteria. Excellent quantitative agreement between experiments with Bacillus subtilis and a mathematical model reveals that bacterial rheotaxis is a purely physical phenomenon, in contrast to fish rheotaxis but in the same way as sperm rheotaxis. This previously unrecognized bacterial taxis results from a subtle interplay between velocity gradients and the helical shape of flagella, which together generate a torque that alters a bacterium's swimming direction. Because this torque is independent of the presence of a nearby surface, bacterial rheotaxis is not limited to the immediate neighborhood of liquid-solid interfaces, but also takes place in the bulk fluid. We predict that rheotaxis occurs in a wide range of bacterial habitats, from the natural environment to the human body, and can interfere with chemotaxis, suggesting that the fitness benefit conferred by bacterial motility may be sharply reduced in some hydrodynamic conditions.     

The heterogeneous motility of the Lyme disease spirochete in gelatin mimics dissemination through tissue

The Lyme disease spirochete Borrelia burgdorferi exists in nature in an enzootic cycle that involves the arthropod vector Ixodes scapularis and mammalian reservoirs. To disseminate within and between these hosts, spirochetes must migrate through complex, polymeric environments such as the basement membrane of the tick midgut and the dermis of the mammal. To date, most research on the motility of B. burgdorferi has been done in media that do not resemble the tissue milieus that B. burgdorferi encounter in vivo. Here we show that the motility of Borrelia in gelatin matrices in vitro resembles the pathogen's movements in the chronically infected mouse dermis imaged by intravital microscopy. More specifically, B. burgdorferi motility in mouse dermis and gelatin is heterogeneous, with the bacteria transitioning between at least three different motility states that depend on transient adhesions to the matrix. We also show that B. burgdorferi is able to penetrate matrices with pore sizes much smaller than the diameter of the bacterium. We find a complex relationship between the swimming behavior of B. burgdorferi and the rheological properties of the gelatin, which cannot be accounted for by recent theoretical predictions for microorganism swimming in gels. Our results also emphasize the importance of considering borrelial adhesion as a dynamic rather than a static process.     

Structural characterization of mRNA-tRNA translocation intermediates

Cryo-EM analysis of a wild-type Escherichia coli pretranslocational sample has revealed the presence of previously unseen intermediate substates of the bacterial ribosome during the first phase of translocation, characterized by intermediate intersubunit rotations, L1 stalk positions, and tRNA configurations. Furthermore, we describe the domain rearrangements in quantitative terms, which has allowed us to characterize the processivity and coordination of the conformational reorganization of the ribosome, along with the associated changes in tRNA ribosome-binding configuration. The results are consistent with the view of the ribosome as a molecular machine employing Brownian motion to reach a functionally productive state via a series of substates with incremental changes in conformation.     

Two distinct overstretched DNA structures revealed by single-molecule thermodynamics measurements

Double-stranded DNA is a dynamic molecule whose structure can change depending on conditions. While there is consensus in the literature about many structures DNA can have, the state of highly-stretched DNA is still not clear. Several groups have shown that DNA in the torsion-unconstrained B-form undergoes an “overstretching” transition at a stretching force of around 65 pN, which leads to approximately 1.7-fold elongation of the DNA contour length. Recent experiments have revealed that two distinct structural transitions are involved in the overstretching process: (i) a hysteretic “peeling” off one strand from its complementary strand, and (ii) a nonhysteretic transition that leads to an undetermined DNA structure. We report the first simultaneous determination of the entropy (ΔS) and enthalpy changes (ΔH) pertaining to these respective transitions. For the hysteretic peeling transition, we determined ΔS ∼ 20 cal/(K.mol) and ΔH ∼ 7 kcal/mol. In the case of the nonhysteretic transition, ΔS ∼ -3 cal/(K.mol) and ΔH ∼ 1 kcal/mol. Furthermore, the response of the transition force to salt concentration implies that the two DNA strands are spatially separated after the hysteretic peeling transition. In contrast, the corresponding response after the nonhysteretic transition indicated that the strands remained in close proximity. The selection between the two transitions depends on DNA base-pair stability, and it can be illustrated by a multidimensional phase diagram. Our results provide important insights into the thermodynamics of DNA overstretching and conformational structures of overstretched DNA that may play an important role in vivo.