Nanomaterials based on chitosan have emerged as promising carriers of therapeutic agents for drug delivery due to good biocompatibility, biodegradability, and low toxicity. Chitosan originated ...nanocarriers have been prepared by mini-emulsion, chemical or ionic gelation, coacervation/precipitation, and spray-drying methods. As alternatives to these traditional fabrication methods, self-assembled chitosan nanomaterials show significant advantages and have received growing scientific attention in recent years. Self-assembly is a spontaneous process by which organized structures with particular functions and properties could be obtained without additional complicated processing or modification steps. In this review, we focus on recent progress in the design, fabrication and physicochemical aspects of chitosan-based self-assembled nanomaterials. Their applications in drug delivery of different therapeutic agents are also discussed in details.
This paper reviews the previous work on phase change cold storage for air-conditioning systems focusing on two aspects including phase change materials (PCMs) and applications. Besides the studies on ...phase change cold storage devices, the typical air-conditioning systems with cold storage are also reviewed, namely the solar air-conditioning system with cold storage, latent cooling storage and transport system and mixed cold storage air-conditioning system. Moreover, the problems with respect to compatibility, heat transfer enhancement, phase change properties of composite PCMs, etc., are discussed for further investigation.
Chloroplasts and mitochondria contain their own genomes and transcriptional and translational systems. Establishing these genetic systems is essential for plant growth and development. Here we ...characterized a mutant form of a Val-tRNA synthetase (OsValRS2) from Oryza sativa that is targeted to both chloroplasts and mitochondria. A single base change in OsValRS2 caused virescent to albino phenotypes in seedlings and white panicles at heading. We therefore named this mutant white panicle 1 (wp1). Chlorophyll autofluorescence observations and transmission electron microscopy analyses indicated that wp1 mutants are defective in early chloroplast development. RNA-seq analysis revealed that expression of nuclear-encoded photosynthetic genes is significantly repressed, while expression of many chloroplast-encoded genes also changed significantly in wp1 mutants. Western-blot analyses of chloroplast-encoded proteins showed that chloroplast protein levels were reduced in wp1 mutants, although mRNA levels of some genes were higher in wp1 than in wild type. We found that wp1 was impaired in chloroplast ribosome biogenesis. Taken together, our results show that OsValRS2 plays an essential role in chloroplast development and regulating chloroplast ribosome biogenesis.
PIWI (P element induced wimpy testis) integrating RNAs (piRNAs) are small non-coding RNAs with the length of approximately 30 nucleotides that plays crucial roles in germ cells and adult stem cells. ...Recently, accumulating data have shown that piRNA and PIWI proteins are involved in tumorigenesis. However, the roles of PIWI proteins and piRNAs in pancreatic cancer are still elusive. Here, we showed that piR-017061 is significantly downregulated in pancreatic cancer patients’ samples and pancreatic cancer cell lines. Furthermore, we studied the function of piR-017061 in pancreatic cancer and our data revealed that piR-017061 inhibits pancreatic cancer cell growth in vitro and in vivo. Moreover, we analyzed the genomic loci around piR-017061 and identified EFNA5 as a novel target of piR-017061. Importantly, our data further revealed a direct binding between piR-017061 and EFNA5 mRNA mediated by PIWIL1. Mechanically, piR-017061 cooperates with PIWIL1 to facilitate EFNA5 mRNA degradation and loss of piR-017061 results in accumulation of EFNA5 which facilitates pancreatic cancer development. Hence, our data provided novel insights into PIWI/piRNA-mediated gene regulation and their function in pancreatic cancer. Since PIWI proteins and piRNA predominately express in germline and cancer cells, our study provided novel therapeutic strategy for pancreatic cancer treatment.
The early detection and accurate histopathological diagnosis of gastric cancer increase the chances of successful treatment. The worldwide shortage of pathologists offers a unique opportunity for the ...use of artificial intelligence assistance systems to alleviate the workload and increase diagnostic accuracy. Here, we report a clinically applicable system developed at the Chinese PLA General Hospital, China, using a deep convolutional neural network trained with 2,123 pixel-level annotated H&E-stained whole slide images. The model achieves a sensitivity near 100% and an average specificity of 80.6% on a real-world test dataset with 3,212 whole slide images digitalized by three scanners. We show that the system could aid pathologists in improving diagnostic accuracy and preventing misdiagnoses. Moreover, we demonstrate that our system performs robustly with 1,582 whole slide images from two other medical centres. Our study suggests the feasibility and benefits of using histopathological artificial intelligence assistance systems in routine practice scenarios.
Abstract
Linear (Met1-linked) ubiquitination is involved inflammatory and innate immune signaling. Previous studies have characterized enzymes regulating the addition and removal of this modification ...in mammalian systems. However, only a few plant-derived deubiquitinases targeting Met1-linked ubiquitin chains have been reported and their mechanism of action remains elusive. Here, using a dehydroalanine-bearing Met1-diubiquitin suicide probe, we discover OTUB1 from
Oryza sativa
(OsOTUB1) as a Met1-linked ubiquitin chain-targeting deubiquitinase. By solving crystal structures of apo OsOTUB1 and an OsOTUB1/Met1-diubiquitin complex, we find that Met1 activity is conferred by Met1-specific motifs in the S1’ pocket of OsOTUB1. Large-scale sequence alignments and hydrolysis experiments provide evidence that these motifs are a general determinant of Met1 activity in the OTUB subfamily across species. Analysis of the species distribution of OTUBs capable of hydrolysing Met1-linked ubiquitin chains shows that this activity is conserved in green plants (
Viridiplantae
) and does not exist in metazoans, providing insights into the evolutionary differentiation between primitive plants and animals.
The construction of circularly polarized luminescence (CPL) switches with multiple switchable emission states and high dissymmetry factors (glum) has attracted increasing attention due to their broad ...applications in diverse fields such as the development of smart devices and sensors. Herein, a new family of AIE‐active chiral 3rotaxanes were designed and synthesized, from which a novel CPL switching system was successfully constructed. The switching process was realized through the controlled motions of the chiral pillar5arene macrocycles along the axle through the addition or removal of the acetate anions, which not only modulated the chirality information transfer but also tuned the aggregations of the integrated 3rotaxanes, thus resulting in reversible transformations between two emission states with both high photoluminescence quantum yields (PLQYs) and high dissymmetry factors (glum) values.
The marriage of a switchable rotaxane and an AIEgen gave rise to the successful construction of a novel chiral 3rotaxane‐based CPL switching system with large glum values, remarkable difference in the glum values, and excellent cycling ability.
The aim of this study was to evaluate the angiographic efficacy and clinical outcomes of the Restore paclitaxel-coated balloon in a randomized trial designed to enable its approval with an indication ...for small-vessel disease (SVD).
Higher rates of restenosis and stent thrombosis limit the effectiveness of drug-eluting stent (DES) treatment of SVD. Whether a drug-coated balloon (DCB)-only strategy is effective in de novo SVD is not yet established.
In the noninferiority RESTORE SVD China trial, eligible patients with reference vessel diameter ≥2.25 and ≤2.75 mm were randomized to the Restore DCB or the RESOLUTE Integrity DES in a 1:1 ratio stratified by diabetes and number of lesions treated. Patients with RVD ≥2.00 and <2.25 mm were enrolled in a nested very small vessel registry. Angiographic and clinical follow-up were planned at 9 months and 1 year, respectively, in all patients. The study was powered for the primary endpoint of 9-month in-segment percentage diameter stenosis.
Between August 2016 and June 2017, a total of 230 subjects at 12 sites were randomized to the DCB group (n = 116) or DES group (n = 114); 32 patients were treated with the DCB in the very small vessel cohort. Nine-month in-segment percentage diameter stenosis was 29.6 ± 2.0% with the DCB versus 24.1 ± 2.0% with the DES; the 1-sided 97.5% upper confidence limit of the difference was 10.9%, achieving noninferiority of the DCB compared with the DES (p for noninferiority < 0.001). The DCB and DES had comparable 1-year rates of target lesion failure (4.4% vs. 2.6%, p = 0.72).
In this multicenter randomized trial, the Restore DCB was noninferior to the RESOLUTE DES for 9-month in-segment percentage diameter stenosis. (Assess the Efficacy and Safety of RESTORE Paclitaxel Eluting Balloon Versus RESOLUTE Zotarolimus Eluting Stent for the Treatment of Small Coronary Vessel Disease; NCT02946307).
Granulomatous diseases caused by Nocardia seriously endanger the health of cultured fish. These bacteria are widely distributed, but prevention and treatment methods are very limited. Chronic ...granulomatous inflammation is an important pathological feature of Nocardia infection. However, the molecular mechanisms of granuloma formation and chronic inflammation are still unclear. Constructing a granuloma infection model of Nocardia is the key to exploring the pathogenesis of the disease. In this study, we established a granuloma model in the liver of largemouth bass (Micropterus salmoides) and assessed the infection process of Nocardia seriolae at different concentrations by analysing relevant pathological features. By measuring the expression of pro‐inflammatory cytokines, transcription factors and a pyroptosis‐related protein, we revealed the close relationship between pyroptosis and chronic inflammation of granulomas. We further analysed the immunofluorescence results and the expression of pyroptosis‐related protein of macrophage infected by N. seriolae and found that N. seriolae infection induced macrophage pyroptosis in vitro. These results were proved by flow cytometry analysis of infection experiment in vivo. Our results indicated that the pyroptosis effect may be the key to inducing chronic inflammation in the fish liver and further mediating granuloma formation. In this study, we explored the molecular mechanism underlying chronic inflammation of granulomas and developed research ideas for understanding the occurrence and development of granulomatous diseases in fish.
In order to finely characterize the physical properties and seepage characteristics of underwater distributary channel sand bodies in a braided river delta, the particle size distribution, mercury ...injection, and withdrawal of low, medium, high, and extra-high permeability core samples from the TIII reservoir from 15 core wells in the Sangtamu Oilfield were compared. The pore-throat characteristics of the rocks with different deposition modes and their effects on the fluid seepage were analyzed from the perspective of the deposition processes. The statistical results revealed that the rocks formed in a continuous and stable strong hydrodynamic environment were coarse grained. The seepage capacities of the rock increased as the maximum throat radius connecting with the pores increased. The mercury withdrawal efficiency decreased as the difference between the throat radius and pore radius increased. The percentage of the throat volume without effective seepage to the total volume of the pore-throat system increased as the permeability of the samples increased. Therefore, when characterizing reservoirs based on the porosity and permeability, it is important to differentiate the energy of the hydrodynamic depositional environment of a monogenic sand body in order to improve the accuracy of the understanding of the reservoirs.