Emerging SARS-CoV-2 variants of concern (VOCs) harboring multiple mutations in the spike protein raise concerns on effectiveness of current vaccines that rely on the ancestral spike protein. Here, we ...design a quadrivalent mosaic nanoparticle vaccine displaying spike proteins from the SARS-CoV-2 prototype and 3 different VOCs. The mosaic nanoparticle elicits equivalent or superior neutralizing antibodies against variant strains in mice and non-human primates with only small reduction in neutralization titers against the ancestral strain. Notably, it provides protection against infection with prototype and B.1.351 strains in mice. These results provide a proof of principle for the development of multivalent vaccines against pandemic and potential pre-emergent SARS-CoV-2 variants.
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•Sulfide (20 mg L−1) could reduce the specific anammox activity by 61.7%.•Protein-like substances were quenched due to sulfide stress.•Sulfide addition led Candidatus Kuenenia ...decrease while Thiobacillus increase.•Functional gene abundances significantly decreased with 20 mg L−1 sulfide.
Sulfide has attracted increasing attention due to its odor nuisance, toxicity and corrosion. Although variations in the nitrogen removal performance of anammox under sulfide stress have been reported previously, understanding the microorganisms at the molecular level is of greater significance. This study first deciphered the microbial community and functional gene response of anammox sludge to sulfide stress. Results showed that 20 mg L−1 sulfide could reduce specific anammox activity by 61.7%. The protein-like substances within extracellular polymeric substances were quenched at the end of the experiment. Moreover, the relative abundance of Candidatus Kuenenia significantly decreased from 28.7% to 6.4% while Thiobacillus increased from 0 to 7.2% due to sulfide stress. Furthermore, the abundances of functional genes (hzsA, hdh, nirK and nirS) significantly decreased when the sulfide concentration reached 20 mg L−1. These findings provide a further theoretical basis for the anammox process for nitrogen removal from wastewater containing sulfide.
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•Long-term effects of Fe3O4 NPs on anammox UASB reactor were firstly investigated.•The anammox performance was not obviously influenced under exposure of 2−200 mg L−1 Fe3O4 NPs.•The ...sludge characteristics were increased with Fe3O4 NPs concentration elevated.•The Fe3O4 NPs could enhance the relative abundance of Candidatus Kuenenia.
The performance of anaerobic ammonium oxidation (anammox) granules were studied under long-term exposure to Fe3O4 NPs. The Fe3O4 NPs had no negative impacts on nitrogen removal performance with the addition of 2−200 mg L−1. The specific anammox activity (SAA) slightly decreased from 287.0 ± 13.2 to –253.0 ± 9.2 mg TN g-1VSS d-1 with the increase in Fe3O4 NPs level from 2 to 60 mg L-1, and then significantly enhanced to 381.8 ± 15.7 mg TN g-1VSS d-1 at 200 mg L-1 Fe3O4 NPs. And the change trends of the heme c content, extracellular polymeric substance amount and settling velocity were consistent with that of SAA. The Candidatus_Kuenenia was the dominant species during the entire experiment and its relative abundance was up to 33.4 % at the end the experiment. The results provide some useful information for comprehending the impact of Fe3O4 NPs on the performance of wastewater biological treatment systems.
Gasdermin D (GSDMD) serves as a key executor to trigger pyroptosis and is emerging as an attractive checkpoint in host defense, inflammatory, autoimmune diseases, and many other systemic diseases. ...Although canonical and non-canonical inflammasome-mediated classic GSDMD cleavage, GSDMD-NT migration to cell membrane, GSDMD-NT oligomerization, and pore forming have been well recognized, a few unique features of GSDMD in specific condition beyond its classic function, including non-lytic function of GSDMD, the modification and regulating mechanism of GSDMD signaling have also come to great attention and played a crucial role in biological processes and diseases. In the current review, we emphasized the GSDMD protein expression, stabilization, modification, activation, pore formation, and repair during pyroptosis, especially the regulation and modification of GSDMD signaling, such as GSDMD complex in polyubiquitination and non-pyroptosis release of IL-1β, ADP-riboxanation, NINJ1 in pore forming, GSDMD binding protein TRIM21, GSDMD succination, and Regulator-Rag-mTOR-ROS regulation of GSDMD. We also discussed the novel therapeutic strategies of targeting GSDMD and summarized recently identified inhibitors with great prospect.
Microglia-mediated neuroinflammation is involved in various neurological diseases, including ischemic stroke, but the endogenous mechanisms preventing unstrained inflammation is still unclear. The ...anti-inflammatory role of transcription factor nuclear receptor subfamily 4 group A member 1 (NR4A1) in macrophages and microglia has previously been identified. However, the endogenous mechanisms that how NR4A1 restricts unstrained inflammation remain elusive. Here, we observed that NR4A1 is up-regulated in the cytoplasm of activated microglia and localizes to processing bodies (P-bodies). In addition, we found that cytoplasmic NR4A1 functions as an RNA-binding protein (RBP) that directly binds and destabilizes Tnf mRNA in an N6-methyladenosine (m6A)-dependent manner. Remarkably, conditional microglial deletion of Nr4a1 elevates Tnf expression and worsens outcomes in a mouse model of ischemic stroke, in which case NR4A1 expression is significantly induced in the cytoplasm of microglia. Thus, our study illustrates a novel mechanism that NR4A1 posttranscriptionally regulates Tnf expression in microglia and determines stroke outcomes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Given the increasing applications of NiO nanoparticles (NPs) in battery products, the potential effects of NiO NPs on anaerobic ammonium oxidation (anammox) systems were studied for the first time. ...The results showed that the anammox system performance obviously differed under the stresses of different NiO NPs concentrations. After the withdrawal of NiO NPs, the nitrogen removal performance of the anammox reactor returned to nearly that of the initial phase within 35 days. Compared with 0 mg L−1 NiO NPs, the specific anammox activity first increased and then decreased to the minimum value of 116.8 ± 13.8 mg TN g−1 VSS d−1 at 60 mg L−1 NiO NPs. The variations in the heme c contents and extracellular polymeric substance amounts were similar to the variations in the specific anammox activity throughout the whole experiment. Additionally, the relative abundance of the dominant bacteria (Candidatus kuenenia) increased from 20.44% at 60 mg L−1 NiO NPs to 23.14% at the end of the last phase. Thus, the potential effects of NiO NPs on anammox systems should be a cause for great concern.
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•Long-term effects of NiO NPs on the anammox system were firstly investigated.•The anammox performance was enhanced below 10 mg L−1 NiO NPs and suppressed by 10–60 mg L−1 NiO NPs.•The stability of the reactor operation could be controlled by the (F/M)/SAA ratio.•“Ca. kuenenia” dominated the community in the presence of 1–60 mg L−1 NiO NPs.•The performance of the anammox reactor could recover after withdrawing the NiO NPs.
•Inhibitory effects of Cu(II) and Zn(II) on SAA were evaluated using RSM.•Pre-exposure to Cu(II) without substrates strongly inhibited anammox activity.•Pre-exposure to Cu(II) in the presence of ...NO2−–N enhanced inhibition.•The cumulative toxicity of Cu(II) was mitigated by intermittent exposure.
This study evaluated the interactive effect of Cu(II) and Zn(II) on anaerobic ammonium oxidation (anammox) activity using response surface methodology with a central composite design. A regression model equation was developed and validated to predict the normalized anammox activity (NAA) of anammox granules exposed to various heavy metal concentrations. The joint inhibitory effect tended to exacerbate initially and reversed as the concentrations increased and then moderated again. The most severe inhibition, resulting in a NAA of 20.1%, occurred at Cu(II) and Zn(II) concentrations of 16.3 and 20.0mgL−1, respectively. Notably, the cumulative toxicity was mitigated with the aid of intermittent exposure acclimatization. Additionally, pre-exposure to Cu(II) in the absence of substrates strongly inhibited anammox activity. However, the presence of NO2− significantly enhanced Cu(II) inhibition. Therefore, such conditions should be avoided to minimize the disturbance of the anammox process.
► Anammox is a new process for monosodium glutamate (MSG) wastewater nitrogen removal. ► Conventional activated sludge can be the seeding source for MSG wastewater treatment. ► Sludge from the MSG ...wastewater treatment plant was the best seeding sludge.
Three activated sludges from a landfill leachate treatment plant (S1), a municipal sewage treatment plant (S2) and a monosodium glutamate (MSG) wastewater treatment plant (S3) were used as inocula to enrich anaerobic ammonium oxidation (anammox) bacteria for the startup of MSG industrial wastewater treatment system. After 360 days of cultivation using MSG wastewater, obvious anammox activity was observed in all three cultures. The maximum specific anammox activities of cultures S1, S2 and S3 were 0.11
kg
N
kg
−1
VSS
day
−1, 0.09
kg
N
kg
−1
VSS
day
−1 and 0.16
kg
N
kg
−1
VSS
day
−1, respectively. Brownish-red anammox granules having diameters in the range of 0.2–1.0
mm were visible in cultures S1 and S2, and large red granules having diameters in the range of 0.5–2.5
mm were formed in culture S3 after 420 days of cultivation. Phylogenetic analysis of 16S rRNA genes showed that
Kuenenia organisms were the dominant anammox species in all three cultures. The copy numbers of 16S rRNA genes of anammox bacteria in cultures S1, S2 and S3 were 6.8
×
10
7
copies
mL
−1, 9.4
×
10
7
copies
mL
−1 and 7.5
×
10
8
copies
mL
−1, respectively. The results of this study demonstrated that anammox cultivation from conventional activated sludges was highly possible using MSG wastewater. Thus the anammox process has possibility of applying to the nitrogen removal from MSG wastewater.
•The effect of oxytetracycline on anammox performance and microbial communities was investigated.•The changes in properties of anammox granules under oxytetracycline stress were observed.
The effect ...of oxytetracycline (OTC) on anaerobic ammonium oxidation (anammox) performance and the evolution of anammox consortia under OTC stress were analyzed in this study. Meanwhile, the level of resistance genes under OTC stress was monitored for the first time in the anammox system. The nitrogen removal capacity of anammox reactor was almost deprived within three weeks under the stress of 2mgL−1 OTC, accompanied by a significant reduction of specific anammox activity of 81.3% and heme c content of 50.1%. However, the abundance of hydrazine synthase gene was adversely affected, with a loss of 29.7%. The efflux pump antibiotic resistance genes tetA, tetB, and tetC and the enzymatic modification gene tetX were first detected in anammox mixed culture. The abundance of tetA was increased from 1.03 to 2.51%. The ratios of tetB and tetC doubled, while there was no obvious change in the ratios of tetX. Therefore, it can be inferred that anammox microorganisms resisted the biotoxicity of OTC via efflux pumping mechanism. After the withdrawal of OTC from the influent, the nitrogen removal capacity of anammox reactor recovered, and the abundance of resistance genes declined gradually.
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