MicroRNAs (miRNAs) belong to a class of small non-coding RNAs that regulate numerous biological processes by targeting a broad set of messenger RNAs. Recently, miRNAs have been detected in remarkably ...stable forms in many types of body fluids. A comparison between cancer patients and healthy individuals has clearly shown that certain types of circulating miRNAs are associated with cancer initiation and progression. Research on miRNA-based biomarkers has witnessed phenomenal growth, owing to the non-invasive nature of miRNA-based screening assays and their sensitivity and specificity in detecting cancers. Consequently, a considerable effort has been devoted to identify suitable miRNAs for cancer diagnosis and also decode the information carried by circulating miRNAs. This review highlights the current studies that focus on the identification of circulating miRNA-based diagnostic and prognostic markers, for the most prevalent types of cancer. Additionally, the review also provides an insight into the putative functions of miRNAs, and attempts to delineate the mechanisms through which they are released into the bloodstream. Moreover, methodologies and strategies for identification of circulating miRNAs in cancers are summarized. Finally, potential strategies for circulating miRNA-based cancer therapies are proposed.
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Schistosome infection persists for decades. Parasites are in close contact with host peripheral blood immune cells, yet little is known about the regulatory interactions between parasites and these ...immune cells. Here, we report that extracellular vesicles (EVs) released from Schistosoma japonicum are taken up primarily by macrophages and other host peripheral blood immune cells and their miRNA cargo transferred into recipient cells. Uptake of S. japonicum EV miR-125b and bantam miRNAs into host cells increased macrophage proliferation and TNF-α production by regulating the corresponding targets including Pros1, Fam212b, and Clmp. Mice infected with S. japonicum exhibit an increased population of monocytes and elevated levels of TNF-α. Reduction of host monocytes and TNF-α level in S. japonicum infected mice led to a significant reduction in worm and egg burden and pathology. Overall, we demonstrate that S. japonicum EV miRNAs can regulate host macrophages illustrating parasite modulation of the host immune response to facilitate parasite survival. Our findings provide valuable insights into the schistosome-host interaction which may help to develop novel intervention strategies against schistosomiasis.
•Simultaneous SCFAs and acetic acid increments were accomplished.•The superior degradation effect of microcystin-LR was achieved.•Synergistic effect occurred when DBD coupled with CaO2.•e-aq, 1O2, ...•OH, •O2–, and ONOO– were identified to be functional active species.
The recycling of high-value carbon resources from waste cyanobacteria is an interesting research direction. In this study, the feasibility of barrier discharge plasma coupled with calcium peroxide (DBD/CaO2) as a novel pretreatment method to improve the quantity and quality of short chain fatty acids (SCFAs) in anaerobic fermentation of cyanobacteria was explored. The relatively excellent SCFAs and acetic acid production were obtained in DBD (58.5 W, 30 min)/CaO2 (0.09 g/g VSS) group, which were 6.7 and 7.5 times that of the control, respectively. DBD and CaO2 synergistically improved the solubilization of cyanobacteria polymers. Cell rupture occurs under the combined influence of physicochemical effect and intracellular oxidative stress. DBD/CaO2 was beneficial to reduce the adverse effect of humus on anaerobic fermentation and improve the biodegradability of dissolved organic matter. The accumulation of microorganisms related to hydrolysis and acidification and the reduction of SCFAs/acetic acid consumers were also related with the accumulation of SCFAs/acetic acid. DBD/CaO2 treatment achieved a 73.2 % removal rate of microcystin-LR on the 5th day of anaerobic fermentation. The contribution order of functional active species to cyanobacteria solubilization and microcystin-LR degradation was e-aq > •OH >1O2 > •O-2·O2-·O2- > ONOO– and e-aq > •OH > •O-2 >1O2 > ONOO–, respectively. Finally, the synergistic mechanism of DBD and CaO2 in cyanobacteria anaerobic fermentation was expounded. This work provides an attractive and promising technology to recover valuable carbon sources from cyanobacteria.
The strontium (Sr) substitution plays critical roles in physical-chemical-biological properties of hydroxyapatite (HA) bioceramics due to the structural distortion induced by doping. Herein, the ...effects of Sr substitution on the structural distortion of HA were investigated systematically by Rietveld refinement and Raman spectroscopy. We compared the occupation possibility of Sr in the lattice and pointed out its preferred occupancy. The effects of doping on lattice parameters, bond length, bond angle and crystallite size were also studied. The evidence, that doping will give rise to the distorted structure, has been shown. In addition, the PO43−, Ca-PO4 and OH− vibrations were further studied to verify the structural evolution and distortion. This work may be helpful in further studying on the structure-property relationship of Sr substitution HA.
A new class of highly potent NS5A inhibitors with an unsymmetric benzimidazole-difluorofluorene-imidazole core and distal 2.2.1azabicyclic ring system was discovered. Optimization of antiviral ...potency and pharmacokinetics led to the identification of 39 (ledipasvir, GS-5885). Compound 39 (GT1a replicon EC50 = 31 pM) has an extended plasma half-life of 37-45 h in healthy volunteers and produces a rapid >3 log viral load reduction in monotherapy at oral doses of 3 mg or greater with once-daily dosing in genotype 1a HCV-infected patients. 39 has been shown to be safe and efficacious, with SVR12 rates up to 100% when used in combination with direct-acting antivirals having complementary mechanisms.
RNA interference through non-coding microRNAs (miRNAs) represents a vital component of the innate antiviral immune response in plants and invertebrate animals; however, a role for cellular miRNAs in ...the defence against viral infection in mammalian organisms has thus far remained elusive. Here we show that interferon beta (IFN ) rapidly modulates the expression of numerous cellular miRNAs, and that eight of these IFN -induced miRNAs have sequence-predicted targets within the hepatitis C virus (HCV) genomic RNA. The introduction of synthetic miRNA-mimics corresponding to these IFN -induced miRNAs reproduces the antiviral effects of IFN on HCV replication and infection, whereas neutralization of these antiviral miRNAs with anti-miRNAs reduces the antiviral effects of IFN against HCV. In addition, we demonstrate that IFN treatment leads to a significant reduction in the expression of the liver-specific miR-122, an miRNA that has been previously shown to be essential for HCV replication. Therefore, our findings strongly support the notion that mammalian organisms too, through the interferon system, use cellular miRNAs to combat viral infections.
The excessive ammonia produced in pond aquaculture processes cannot be ignored. In this review, we present the distribution and diversity of ammonia-oxidizing archaea (AOA) and anaerobic ...ammonia-oxidizing bacteria (AnAOB) in the pond environment. Combined with environmental conditions, we analyze the advantages of AOA and AnAOB in aquaculture water treatment and discuss the current situation of pond water treatment engineering involving these microbes. AOA and AnAOB play an important role in the nitrogen removal process of aquaculture pond water, especially in seasonal low temperatures and anoxic sediment layers. Finally, we prospect the application of bioreactors to purify pond aquaculture water using AOA and AnAOB, in autotrophic nitrogen removal, which can reduce the production of greenhouse gases (such as nitrous oxide) and is conducive to the development of environmentally sustainable pond aquaculture.
Abstract
Grass carp,
Ctenopharyngodon idella
, is the largest freshwater aquaculture fish species worldwide. However, its environmental impacts are increasingly controversial. In this paper, we ...considered the production of a 1500 g commercial grass carp as an example, analyzed through a life cycle assessment. The results showed that the indicators of global warming potential (GWP), acidification potential, eutrophication potential, freshwater eco‐toxicity potential (FAETP), land competition (LC), and fossil energy consumption of producing 1 kg of grass carp were equivalent to 5.7267 kg of CO
2
, 0.0648 kg of 1,4‐DCB0, 0.0010 kg of P, 0.0276 kg of SO
2
, 8.2951 m
2
, 0.3491 kg of oil, respectively, and were mainly from feed processing and water pollution. Compared with pig, beef, and sheep production, grass carp production has lower environmental impacts, but in terms of GWP, FAETP, and LC were significantly higher than chicken production, especially water pollution and discharge, which is an important consideration. This study clarifies the direction of grass carp production and key focus areas include producing low carbon and nitrogen emission feed, application of ecological engineering aquaculture system, intelligent mechanization technology and equipment.
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Treatment of hepatitis C virus (HCV) infection has been historically challenging due the high viral genetic complexity wherein there are eight distinct genotypes and at least 86 viral ...subtypes. While HCV NS3/4A protease inhibitors are an established treatment option for genotype 1 infection, limited coverage of genotypes 2 and/or 3 combined with serum alanine transaminase (ALT) elevations for some compounds has limited the broad utility of this therapeutic class. Our discovery efforts were focused on identifying an NS3/4A protease inhibitor with pan-genotypic antiviral activity, improved coverage of resistance associated substitutions, and a decreased risk of hepatotoxicity. Towards this goal, distinct interactions with the conserved catalytic triad of the NS3/4A protease were identified that improved genotype 3 antiviral activity. We further discovered that protein adduct formation strongly correlated with clinical ALT elevation for this therapeutic class. Improving metabolic stability and decreasing protein adduct formation through structural modifications ultimately resulted in voxilaprevir. Voxilaprevir, in combination with sofosbuvir and velpatasvir, has demonstrated pan-genotypic antiviral clinical activity. Furthermore, hepatotoxicity was not observed in Phase 3 clinical trials with voxilaprevir, consistent with our design strategy. Vosevi® (sofosbuvir, velpatasvir, and voxilaprevir) is now an approved pan-genotypic treatment option for the most difficult-to-cure individuals who have previously failed direct acting antiviral therapy.
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