Fungal pathogens represent a major group of plant invaders that are the causative agents of many notorious plant diseases. Large quantities of RNAs, especially small RNAs involved in gene silencing, ...have been found to transmit bidirectionally between fungal pathogens and their hosts. Although host-induced gene silencing (HIGS) technology has been developed and applied to protect crops from fungal infections, the mechanisms of RNA transmission, especially small RNAs regulating trans-kingdom RNA silencing in plant immunity, are largely unknown. In this review, we summarize and discuss recent important findings regarding trans-kingdom sRNAs and RNA silencing in plant–fungal pathogen interactions compared with the well-known RNAi mechanisms in plants and fungi. We focus on the interactions between plant and fungal pathogens with broad hosts, represented by the vascular pathogen Verticillium dahliae and non-vascular pathogen Botrytis cinerea, and discuss the known instances of natural RNAi transmission between fungal pathogens and host plants. Given that HIGS has been developed and recently applied in controlling Verticillium wilt diseases, we propose an ideal research system exploiting plant vasculature–Verticillium interaction to further study trans-kingdom RNA silencing.
We summarize recent advances on natural trans-kingdom sRNAs and RNA silencing in plant–fungal pathogen interactions. We discuss the mode of RNAi signal transmission between plant and fungal pathogens compared with RNAi mechanisms in plants and fungi. We propose that plant vascular tissues infected by vascular fungal pathogen would be an ideal system for further investigations of trans-kingdom RNA silencing.
The incorporation of pentagon‐heptagon pairs into helical nanographenes lacks a facile synthetic route, and the impact of these pairs on chiroptical properties remains unclear. In this study, a ...method for the stepwise construction of pentagon‐heptagon pairs in helical nanographenes by the dehydrogenation of 6helicene units was developed. Three helical nanographenes containing pentagon‐heptagon pairs were synthesized and characterized using this approach. A wide variation in the molecular geometries and photophysical properties of these helical nanographenes was observed, with changes in the helical length of these structures and the introduction of the pentagon‐heptagon pairs. The embedded pentagon‐heptagon pairs reduced the oxidation potential of the synthesized helical nanographenes. The high isomerization energy barriers enabled the chiral resolution of the helicene enantiomers. Chiroptical investigations revealed remarkably enhanced circularly polarized luminescence and luminescence dissymmetry factors with an increasing number of the pentagon‐heptagon pairs.
The controlled dehydrogenation of 6helicene units provides a facile and feasible method for the synthesis of helical nanographenes containing pentagon‐heptagon pairs. The presence of pentagon‐heptagon pairs has proven to be quite effective in modulating the electrochemical and photophysical properties of the resulting nanographenes, including enhanced circularly polarized luminescence.
Recycling of waste concrete has become an important issue worldwide due to the continued increase of construction wastes. Also, the growing global construction activities urge to find sustainable ...resources to replace natural materials for the production of concrete. In the past few decades, many researches have been carried out on the use of recycled aggregate (RA) derived from construction and demolition wastes to produce concrete products. This paper reviews the previous findings on the effects of use of RA on durability of concrete. In general, the amount of adhered mortar and the quality of the original concrete have a significant effect on the properties of resulting concrete. The increase of RA content and w/c ratio results in poorer durability of concrete. In comparison, the negative effect of recycled fine aggregate is more obvious than that of recycled coarse aggregate. The use of pozzolanic materials either for surface coating of RA or intermixed within the concrete are effective and feasible to improve the overall durability of concrete. Recent researches on CO2 treatment indicate that it can enhance the properties of RA and durability of concrete significantly.
Atherosclerosis (AS) is associated with high morbidity and mortality, thus imposing a growing burden on modern society. Herb‐derived bicyclol (BIC) is a versatile bioactive compound that can be used ...to treat AS. However, its efficacy in AS is not yet described. Here, it is shown that BIC normalizes gut microflora dysbiosis induced by a high fat diet in Apoe(−/−) mice. Metagenome‐wide association study analysis verifies that the modulation on carbohydrate‐active enzymes and short‐chain fatty acid generating genes in gut flora is among the mechanisms. The gut healthiness, especially the gut immunity and integrity, is restored by BIC intervention, leading to improved systemic immune cell dynamic and liver functions. Accordingly, the endothelial activation, macrophage infiltration, and cholesterol ester accumulation in the aortic arch are alleviated by BIC to lessen the plaque onset. Moreover, it is proved that the therapeutic effect of BIC on AS is transmissible by fecal microbiota transplantation. The current study, for the first time, demonstrates the antiatherosclerotic effects of BIC and shows that its therapeutic value can at least partially be attributed to its manipulation of gut microbiota.
Bicyclol (BIC) effectively modulates the composition, function, and production of endogenous metabolites of gut microbiota. The gut health reinstated by BIC benefits systemic immune cell dynamics and liver functions, leading to improved chronic inflammation and hypercholesterolemia. Consequently, endothelial activation, macrophage infiltration, and cholesterol ester accumulation in the aortic arch are attenuated, causing less plaque onset.
Macrophages, associated with their heterogenous and dynamic polarization status, actively shape the development of renal fibrosis (RF). In this study, we revealed the significance of a signalling ...axis, circular RNA ACTR2 (circACTR2)/miR‐200c/Yes‐associated protein (YAP), in regulating macrophage polarization and the development of RF. A unilateral urethral obstruction (UUO)‐induced RF model was established in vivo. In vitro, interferon‐γ (IFNγ) and interleukin (IL)‐4 were applied to induce M1 and M2 polarization, respectively. The abundance of M1 and M2 macrophages were examined by immunofluorescence (IF) or flow cytrometry on markers specific for each subtype. Expressions of circACTR2, miR‐200c and YAP were measured by quantitative real‐time‐polymerase chain reaction and/or Western blotting. Interactions between circACTR2, miR‐200c and YAP were examined by combining luciferase assay, RNA immunoprecipitation and IF. Impact of targeting circACTR2 on RF and macrophage polarization was also examined in vivo. UUO‐induced RF was associated with increased M1 and M2 macrophages, up‐regulations of circACTR2 and YAP and the down‐regulation of miR‐200c in the obstructed kidney. circACTR2 was essential for IL‐4‐induced M2 polarization, but not IFNγ‐induced M1 polarization. This activity of circACTR2 was mediated by sponging miR‐200c and activating the downstream YAP signalling. In vivo, knocking down circACTR2 boosted miR‐200c expression, reduced YAP level, lowered M2 macrophages in obstructed kidney and ameliorated UUO‐induced RF. circACTR2, by targeting and sponging miR‐200c, activates YAP signalling, stimulates M2 macrophage polarization and promotes the development of RF. Therefore, targeting circACTR2 may benefit the treatment of RF.
circACTR2 is up‐regulated renal fibrosis, and circACTR2 promotes the development of renal fibrosis by increasing M2 macrophage polarization. Mechanistically, circACTR2 promotes YAP into the nucleus and activates YAP signaling by targeting and sponging miR‐200c, thereby increasing the expression of M2 biomarkers including CD206, Arg‐1, Fizz‐1, and IL‐10.
CRISPR/Cas system has become one of the most powerful techologies in biomedical research, and has showed great potentials in the gene related diseases. However, efficient delivery systems of ...CRISPR/Cas to target cells remains challenging. In recent years, nanoparticles have showned great potentials for the delivery of CRISPR/Cas systems. This paper mainly approaches the development and new strategies of CRISPR/Cas delivery systems, as well as their application in the clinical diseases. By summarizing the CRISPR/Cas systems delivery, new strategies are expected for the gene therapy.
Editorial space: The CRISPR/Cas gene editing system relies on a delivery system to enter the cell so that it can perform its editing function. The CRISPR/Cas9 system can be packaged into viral or non‐viral vectors, which can be expressed in host cells and exert gene editing functions. The combination of nanoparticles and different vectors can promote the delivery of gene editing machinery.
Globally, the incidence of diabetes mellitus (DM) and Alzheimer's disease (AD) is increasing year by year, causing a huge economic and social burden, and their pathogenesis and aetiology have been ...proven to have a certain correlation. In recent years, more and more studies have shown that vacuolar adenosine triphosphatases (v‐ATPases) in eukaryotes, which are biomolecules regulating lysosomal acidification and glycolipid metabolism, play a key role in DM and AD. This article describes the role of v‐ATPase in DM and AD, including its role in glycolysis, insulin secretion and insulin resistance (IR), as well as its relationship with lysosomal acidification, autophagy and β‐amyloid (Aβ). In DM, v‐ATPase is involved in the regulation of glucose metabolism and IR. v‐ATPase is closely related to glycolysis. On the one hand, v‐ATPase affects the rate of glycolysis by affecting the secretion of insulin and changing the activities of key glycolytic enzymes hexokinase (HK) and phosphofructokinase 1 (PFK‐1). On the other hand, glucose is the main regulator of this enzyme, and the assembly and activity of v‐ATPase depend on glucose, and glucose depletion will lead to its decomposition and inactivation. In addition, v‐ATPase can also regulate free fatty acids, thereby improving IR. In AD, v‐ATPase can not only improve the abnormal brain energy metabolism by affecting lysosomal acidification and autophagy but also change the deposition of Aβ by affecting the production and degradation of Aβ. Therefore, v‐ATPase may be the bridge between DM and AD.
Display omitted
Drug resistance is a major obstacle in the field of pre-clinical and clinical therapeutics. The development of novel technologies and targeted therapies have yielded new modalities to ...overcome drug resistance, but multidrug resistance (MDR) remains one of the major challenges in the treatment of cancer. The ubiquitin-proteasome system (UPS) has a central role in regulating the levels and activities of a multitude of proteins as well as regulation of cell cycle, gene expression, response to oxidative stress, cell survival, cell proliferation and apoptosis. Therefore, inhibition of the UPS could represent a novel strategy for the treatment and overcoming of drug resistance in chemoresistant malignancies. In 2003, bortezomib was approved by the FDA for the treatment of multiple myeloma (MM). However, due to its limitations, second generation proteasome inhibitors (PIs) like carfilzomib, ixazomib, oprozomib, delanzomib and marizomib were introduced which displayed clinical activity in bortezomib-resistant tumors. Past studies have demonstrated that proteasome inhibition potentiates the anti-cancer efficacy of other chemotherapeutic drugs by: i) decreasing the expression of anti-apoptotic proteins such as TNF-α and NF-kB, ii) increasing the levels of Noxa, a pro-apoptotic protein, iii) activating caspases and inducing apoptosis, iv) degrading the pro-survival protein, induced myeloid leukemia cell differentiation protein (MCL1), and v) inhibiting drug efflux transporters. In addition, the mechanism of action of the immunoproteasome inhibitors, ONX-0914 and LU-102, suggested their therapeutic role in the combination treatment with PIs. In the current review, we discuss various PIs and their underlying mechanisms in surmounting anti-tumor drug resistance when used in combination with conventional chemotherapeutic agents.
Rhodotorula glutinis is recognized as a biotechnologically important oleaginous red yeast, which synthesizes numerous meritorious compounds with wide industrial usages. One of the most notable ...properties of R. glutinis is the formation of intracellular lipid droplets full of carotenoids. However, the basic genomic features that underlie the biosynthesis of these valuable compounds in R. glutinis have not been fully documented. To reveal the biotechnological potential of R. glutinis, the genomics and lipidomics analysis was performed through the Next-Generation Sequencing and HPLC-MS-based metabolomics technologies.
Here, we firstly assemble the genome of R. glutinis ZHK into 21.8 Mb, containing 30 scaffolds and 6774 predicted genes with a N50 length of 14, 66,672 bp and GC content of 67.8%. Genome completeness assessment (BUSCO alignment: 95.3%) indicated the genome assembly with a high-quality features. According to the functional annotation of the genome, we predicted several key genes involved in lipids and carotenoids metabolism as well as certain industrial enzymes biosynthesis. Comparative genomics results suggested that most of orthologous genes have underwent the strong purifying selection within the five Rhodotorula species, especially genes responsible for carotenoids biosynthesis. Furthermore, a total of 982 lipids were identified using the lipidomics approaches, mainly including triacylglycerols, diacylglyceryltrimethylhomo-ser and phosphatidylethanolamine.
Using whole genome shotgun sequencing, we comprehensively analyzed the genome of R. glutinis and predicted several key genes involved in lipids and carotenoids metabolism. By performing comparative genomic analysis, we show that most of the ortholog genes have undergone strong purifying selection within the five Rhodotorula species. Furthermore, we identified 982 lipid species using lipidomic approaches. These results provided valuable resources to further advance biotechnological applications of R .glutinis.
A copper‐catalyzed difunctionalizing trifluoromethylation of activated alkynes with the cheap reagent sodium trifluoromethanesulfinate (NaSO2CF3 or Langlois’ reagent) has been developed incorporating ...a tandem cyclization/dearomatization process. This strategy affords a straightforward route to synthesis of 3‐(trifluoromethyl)‐spiro4.5trienones, and presents an example of difunctionalization of alkynes for simultaneous formation of two carbon–carbon single bonds and one carbon–oxygen double bond.
Spiro mania: A copper‐catalyzed difunctionalizing trifluoromethylation of activated alkynes with the cheap reagent NaSO2CF3 has been reported, affording a series of 3‐trifluoromethyl spiro4.5trienones through a tandem cyclization/dearomatization process. In this alkyne difunctionalization process, two carbon–carbon bonds and one carbon–oxygen double bond are simultaneously formed.
PDF
