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Diabetic nephropathy (DN) is a serious complication of diabetes mellitus, and persistent inflammation in circulatory and renal tissues is an important pathophysiological basis for DN. ...The essence of the microinflammatory state is the innate immune response, which is central to the occurrence and development of DN. Members of the inflammasome family, including both “receptors” and “regulators”, are key to the inflammatory immune response. Nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) and other inflammasome components are able to detect endogenous danger signals, resulting in activation of caspase-1 as well as interleukin (IL)-1β, IL-18 and other cytokines; these events stimulate the inflammatory cascade reaction, which is crucial for DN. Hyperglycaemia, hyperlipidaemia and hyperuricaemia can activate the NLRP3 inflammasome, which then mediates the occurrence and development of DN through the K+ channel model, the lysosomal damage model and the active oxygen cluster model. In this review, we survey the involvement of the NLRP3 inflammasome in various signalling pathways and highlight different aspects of their influence on DN. We also explore the important effects of the NLRP3 inflammasome on kidney function and structural changes that occur during DN development and progression. It is becoming more evident that NLRP3 inflammasome targeting has therapeutic potential for the treatment of DN.
Summary
Hydrocarbon‐degrading bacteria typically metabolize a broad range of alkane substrates, but global metabolic characteristics of strains growing on alkane substrates in different chain lengths ...remain unclear. In this study, we analysed the transcriptional profiles of a hydrocarbon degrading bacterium, Dietzia sp. DQ12‐45‐1b, during growth on octacosane (C28), hexadecane (C16) and glucose as the sole carbon sources. Our results highlight that C16 and C28 induced common genes of core alkane degradation pathways in DQ12‐45‐1b, whereas transcriptional patterns of genes related to lipid metabolism, energy metabolism, biomass synthesis, and metal ion transportation were distinct. In addition, the transcriptional differences of genes related to glyoxylate shunt (GS) as well as growth phenotypes of mutant strain with defects in GS demonstrated that GS is essential for C16 degradation, though it is dispensable for C28 degradation in DQ12‐45‐1b. These results demonstrate that DQ12‐45‐1b cells exhibited considerable metabolic flexibility by using various mechanisms during growth on alkane substrates in different chain lengths. This study advances our knowledge of microbial hydrocarbon degradation and provides valuable information for the application of alkane‐degrading bacteria in bioremediation and microbial enhanced oil recovery.
Industrial bioethanol production may involve a low pH environment caused by inorganic acids, improving the tolerance of Saccharomyces cerevisiae to a low pH environment is of industrial importance to ...increase ethanol yield, control bacterial contamination, and reduce production cost. In our previous study, acid tolerance of a diploid industrial Saccharomyces cerevisiae strain KF-7 was chronically acclimatized by continuous ethanol fermentation under gradually increasing low-pH stress conditions. Two haploid strains B3 and C3 having excellent low pH tolerance were derived through the sporulation of an isolated mutant. Diploid strain BC3 was obtained by mating these two haploids. In this study, B3, C3, BC3, and the original strain KF-7 were subjected to comparison transcriptome analysis to investigate the molecular mechanism of the enhanced phenotype. The comparison transcriptome analysis results suggested that the upregulated vitamin B1 and B6 biosynthesis contributed to the low pH tolerance. Amino acid metabolism, DNA repairment, and general stress response might also alleviate low pH stress. Saccharomyces cerevisiae seems to employ complex regulation strategies to tolerate low pH during ethanol production. The findings provide guides for the construction of low pH-tolerant industrial strains that can be used in industrial fermentation processes.
Syntrophic oxidization of acetate and propionate are both critical steps of methanogenesis during thermophilic anaerobic digestion. However, knowledge on syntrophic acetate-oxidizing bacteria (SAOB) ...and syntrophic propionate-oxidizing bacteria (SPOB) is limited because of the difficulty in pure culture isolation due to symbiotic relationship. In this study, two thermophilic acetate-fed anaerobic chemostats, ATL (dilution rate of 0.025 day
−1
) and ATH (0.05 day
−1
) and one thermophilic propionate-fed anaerobic chemostat PTL (0.025 day
−1
) were constructed, AOB and POB in these chemostats were studied via microbial community analysis and DNA stable-isotope probing (SIP). The results showed that, in addition to
Tepidanaerobacter
, a known SAOB, species of
Thauera
,
Thermodesulfovibrio
,
Anaerobaculum
,
Ruminiclostridium
,
Comamonas
, and uncultured bacteria belonging to
Lentimicrobiaceae
, o_MBA03,
Thermoanaerobacteraceae
,
Anaerolineaceae
,
Clostridiales
, and
Ruminococcaceae
were determined to be potential AOB in chemostats.
Pelotomaculum
was the key SPOB detected in the propionate-fed chemostat. Based on the intense fluorescence of coenzyme F
420
, majority of
Methanosarcina
cells in acetate-fed chemostats were involved in hydrogenotrophic methanogenesis, suggesting the existence of highly active SAOB among the detected AOB. In the propionate-fed chemostat, most of the species detected as AOB were similar to those detected in the acetate-fed chemostats, suggesting the contribution of the syntrophic acetate oxidization pathway for methane generation. These results revealed the existence of previously unknown AOB with high diversity in thermophilic chemostats and suggested that methanogenesis from acetate via the syntrophic oxidization pathway is relevant for thermophilic anaerobic digestion.
Abstract In this work, we investigate an alternative channel for the formation of fast-spinning black hole–neutron star (BHNS) binaries, in which super-Eddington accretion is expected to occur in ...accreting BHs during the stable mass transfer phase within BH-stripped helium (BH–He-rich) star binary systems. We evolve intensive MESA grids of close-orbit BH–He-rich star systems to systematically explore the projected aligned spins of BHs in BHNS binaries, as well as the impact of different accretion limits on the tidal disruption probability and electromagnetic (EM) signature of BHNS mergers. Most of the BHs in BHNS mergers cannot be effectively spun up through accretion if the accretion rate is limited to ≲ 10 M ̇ Edd , where M ̇ Edd is the standard Eddington accretion limit. In order to reach high spins (e.g., χ BH ≳ 0.5), the BHs are required to be born less massive (e.g., ≲3.0 M ⊙ ) in binary systems with initial periods of ≲0.2–0.3 days and accrete material at ∼ 100 M ̇ Edd . However, even under this high accretion limit, ≳6 M ⊙ BHs are typically challenging to significantly spin up and generate detectable associated EM signals. Our population simulations suggest that different accretion limits have a slight impact on the ratio of tidal disruption events. However, as the accretion limit increases, the EM counterparts from the cosmological BHNS population can become bright overall.
Propionate is one of the major intermediates in anaerobic digestion of organic waste to CO₂ and CH₄. In methanogenic environments, propionate is degraded through a mutualistic interaction between ...symbiotic propionate oxidizers and methanogens. Although temperature heavily influences the microbial ecology and performance of methanogenic processes, its effect on syntrophic interaction during propionate degradation remains poorly understood. In this study, metagenomics and metatranscriptomics were employed to compare mesophilic and thermophilic propionate degradation communities. Mesophilic propionate degradation involved multiple syntrophic organisms (Syntrophobacter, Smithella, and Syntrophomonas), pathways, interactions, and preference toward formate-based electron transfer to methanogenic partners (i.e., Methanoculleus). In thermophilic propionate degradation, one syntrophic organism predominated (Pelotomaculum), interspecies H₂ transfer played a major role, and phylogenetically and metabolically diverse H₂-oxidizing methanogens were present (i.e., Methanoculleus, Methanothermobacter, and Methanomassiliicoccus). This study showed that microbial interactions, metabolic pathways, and niche diversity are distinct between mesophilic and thermophilic microbial communities responsible for syntrophic propionate degradation.
Variation in leaf traits is critical for carbon gains and losses during leaf life and drives litter carbon and nutrient losses via decomposition. Accurately quantifying litter decomposition ...parameters is essential for assessing ecosystem carbon and nutrient dynamics. Leaf litterbags have commonly been employed to measure effects of environmental drivers, decomposers, and plant traits on decomposition rates. There has been much debate regarding the suitability of substituting senesced dead leaves with fresh (green) leaves in litterbags, which has been common practice for mimicking green leaf fall or for practical reasons. Therefore, we tested the null hypothesis that replacement of dead leaves with fresh leaves in litterbag experiments is justified, based on similarities in structural and chemical traits between fresh and dead leaves across plant species and growth forms.
We conducted a paired litterbag decomposition experiment with both fresh and dead leaves of 26 common species in subtropical China, in each of five contrasting ecosystems.
While fresh leaves generally decomposed faster than dead leaves, this deviation varied among species and growth forms, based on their traits. Overall, there was significant but rather weak correlation between dead leaf decomposition rate k and fresh leaf k, across species and ecosystem types; the deviation between fresh and dead leaf k was larger for fast‐decomposing, mostly herbaceous species. The different decomposition patterns for fresh versus dead leaves were underpinned by key underlying traits integrated in leaf resource economics spectra (LES) for fresh and dead leaves. The dead leaf LES exhibited a greater predictive capability for dead leaf k while the fresh leaf LES had higher explanatory value for the fresh leaf k values.
Our findings partly reject the null hypothesis and ask for caution in inferring leaf litter decomposition rates based on green leaf litterbags or traits data. We suggest follow‐up research on substituting senesced roots and stems with fresh ones in decomposition experiments.
Synthesis. Human activities and extreme weather events are leading to increasing pulse inputs of fresh plant parts and our study contributes to knowledge on how they contribute to overall decomposition rates besides senesced litter inputs.
Significant but rather weak correlation exists between leaf decomposition rates (k) of fresh (green) leaves and dead leaves (i.e. litter) across species; the correlation strength varies with growth form (a) but not decomposition site (b). Fresh leaves generally decompose faster than dead ones. Caution is needed in estimating litter decomposition rates using fresh leaf litterbags or fresh leaf traits data.
Common spatial patterns (CSP) is a commonly used method of spatial filtering for multichannel electroencephalogram (EEG) signals. The formulation of the CSP criterion is based on variance using ...L2-norm, which implies that CSP is sensitive to outliers. In this paper, we propose a robust version of CSP, called CSP-L1, by maximizing the ratio of filtered dispersion of one class to the other class, both of which are formulated by using L1-norm rather than L2-norm. The spatial filters of CSP-L1 are obtained by introducing an iterative algorithm, which is easy to implement and is theoretically justified. CSP-L1 is robust to outliers. Experiment results on a toy example and datasets of BCI competitions demonstrate the efficacy of the proposed method.
The production of succinic acid (SA) from biomass has attracted worldwide interest. Saccharomyces cerevisiae is preferred for SA production due to its strong tolerance to low pH conditions, ease of ...genetic manipulation, and extensive application in industrial processes. However, when compared with bacterial producers, the SA titers and productivities achieved by engineered S. cerevisiae strains were relatively low. To develop efficient SA-producing strains, it's necessary to clearly understand how S. cerevisiae cells respond to SA.
In this study, we cultivated five S. cerevisiae strains with different genetic backgrounds under different concentrations of SA. Among them, KF7 and NBRC1958 demonstrated high tolerance to SA, whereas NBRC2018 displayed the least tolerance. Therefore, these three strains were chosen to study how S. cerevisiae responds to SA. Under a concentration of 20 g/L SA, only a few differentially expressed genes were observed in three strains. At the higher concentration of 60 g/L SA, the response mechanisms of the three strains diverged notably. For KF7, genes involved in the glyoxylate cycle were significantly downregulated, whereas genes involved in gluconeogenesis, the pentose phosphate pathway, protein folding, and meiosis were significantly upregulated. For NBRC1958, genes related to the biosynthesis of vitamin B6, thiamin, and purine were significantly downregulated, whereas genes related to protein folding, toxin efflux, and cell wall remodeling were significantly upregulated. For NBRC2018, there was a significant upregulation of genes connected to the pentose phosphate pathway, gluconeogenesis, fatty acid utilization, and protein folding, except for the small heat shock protein gene HSP26. Overexpression of HSP26 and HSP42 notably enhanced the cell growth of NBRC1958 both in the presence and absence of SA.
The inherent activities of small heat shock proteins, the levels of acetyl-CoA and the strains' potential capacity to consume SA all seem to affect the responses and tolerances of S. cerevisiae strains to SA. These factors should be taken into consideration when choosing host strains for SA production. This study provides a theoretical basis and identifies potential host strains for the development of robust and efficient SA-producing strains.
Objective
Withaferin A (WA) is a bioactive compound with a remarkable anti‐cancer effect derived from Withania somnifera, commonly known as ashwagandha. However, the anti‐cancer mechanisms of WA in ...glioblastoma multiforme (GBM) are still unclear.
Materials and Methods
Cell viability assays and xenografted nude mice were used to evaluate the effects of WA, along with flow cytometry to detect apoptosis and cell cycle of GBM. RNA‐seq analysis, Western blotting, immunofluorescence staining, qRT‐PCR and siRNA gene silencing were carried out to determine the signalling pathways affected by WA.
Results
Withaferin A significantly inhibited the growth of GBM in vitro and in vivo and triggered the intrinsic apoptosis of GBM cells by up‐regulating expression of Bim and Bad. WA arrested GBM cells at the G2/M phase of the cell cycle through dephosphorylating Thr161 of CDK1 by activating p53‐independent p21 up‐regulation. Knockdown of p21 restored cell cycle progression and cell viability by down‐regulating the expression of Bad rather than Bim. We demonstrated that endoplasmic reticulum (ER) stress induced by WA through the ATF4‐ATF3‐CHOP axis, initiated apoptosis and G2/M arrest in GBM cells.
Conclusion
We revealed a novel pathway that elucidated WA activation of apoptosis and G2/M arrest in GBM cells through the ATF4‐ATF3‐CHOP axis. This discovery is important for optimization of WA‐based regimens for prevention and/or treatment of GBM.
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