Correction: USP12 promotes antiviral responses by deubiquitinating and stabilizing IFI16.

[This corrects the article DOI: 10.1371/journal.ppat.1011480.].

Research progress of novel bio-denitrification technology in deep wastewater treatment.

Excessive nitrogen emissions are a major contributor to water pollution, posing a threat not only to the environment but also to human health. Therefore, achieving deep denitrification of wastewater is of significant importance. Traditional biological denitrification methods have some drawbacks, including long processing times, substantial land requirements, high energy consumption, and high investment and operational costs. In contrast, the novel bio-denitrification technology reduces the traditional processing time and lowers operational and maintenance costs while improving denitrification efficiency. This technology falls within the category of environmentally friendly, low-energy deep denitrification methods. This paper introduces several innovative bio-denitrification technologies and their combinations, conducts a comparative analysis of their denitrification efficiency across various wastewater types, and concludes by outlining the future prospects for the development of these novel bio-denitrification technologies.

Co-application of biochar and organic amendments on soil greenhouse gas emissions: A meta-analysis.

Biochar has been shown to reduce soil greenhouse gas (GHG) and increase nutrient retention in soil; however, the interaction between biochar and organic amendments on GHG emissions remain largely unclear. In this study, we collected 162 two-factor observations to explore how biochar and organic amendments jointly affect soil GHG emissions. Our results showed that biochar addition significantly increased soil CO2 emission by 8.62 %, but reduced CH4 and N2O emissions by 27.0 % and 23.9 %, respectively. Meanwhile, organic amendments and the co-application with biochar resulted in an increase of global warming potential based on the 100-year time horizon (GWP100) by an average of 18.3 % and 26.1 %. More importantly, the interactive effect of biochar and organic amendments on CO2 emission was antagonistic (the combined effect was weaker than the sum of their individual effects), while additive on CH4 and N2O emissions. Additionally, our results suggested that when biochar is co-applied with organic amendments, soil GHG emissions were largely influenced by soil initial total carbon, soil texture, and biochar feedstocks. Our work highlights the important interactive effects of biochar and organic amendments on soil GHG emissions, and provides new insights for promoting ecosystem sustainability as well as mitigating future climate change.

USP12 promotes antiviral responses by deubiquitinating and stabilizing IFI16.

Deubiquitinating enzymes (DUBs) regulate antiviral immune response through targeting DNA sensor signaling pathway members. As one of the DNA sensors, interferon (IFN)-γ inducible protein 16 (IFI16) play a major role in response to virus infections through activating the canonical STING/TBK-1/IRF3 signaling pathway. Only a few studies discuss the function of DUBs in IFI16-mediated antiviral response. Ubiquitin-specific protease 12 (USP12), which is one of the major members of the USP family, participates in various biological functions. However, whether USP12 regulates the nucleic acid sensor to modulate antiviral immune responses has not yet been elucidated. In this study, we found that knockout or knockdown of USP12 impaired the HSV-1-induced expressions of IFN-ß, CCL-5, IL-6, and downstream interferon-stimulated genes (ISGs). Moreover, USP12 deficiency increased HSV-1 replication and host susceptibility to HSV-1 infection. Mechanistically, USP12 inhibited the proteasome-dependent degradation of IFI16 through its deubiquitinase activity, thereby maintaining IFI16 stability and promoting IFI16-STING-IRF3- and p65-mediated antiviral signaling. Overall, our findings demonstrate an essential role of USP12 in DNA-sensing signaling and contribute to the understanding of deubiquitination-mediated regulation of innate antiviral responses.

The E3 ligase HERC5 promotes antimycobacterial responses in macrophages by ISGylating the phosphatase PTEN.

Innate immune signaling in macrophages during viral infection is regulated by ISGylation, the covalent attachment of the ubiquitin-like protein interferon-stimulated gene 15 (ISG15) to protein targets. Here, we explored the role of ISGylation in the macrophage response to infection with Mycobacterium tuberculosis. In human and mouse macrophages, the E3 ubiquitin ligases HERC5 and mHERC6, respectively, mediated the ISGylation of the phosphatase PTEN, which promoted its degradation. The decreased abundance of PTEN led to an increase in the activity of the PI3K-AKT signaling pathway, which stimulated the synthesis of proinflammatory cytokines. Bacterial growth was increased in culture and in vivo when human or mouse macrophages were deficient in the major E3 ISG15 ligase. The findings expand the role of ISGylation in macrophages to antibacterial immunity and suggest that HERC5 signaling may be a candidate target for adjunct host-directed therapy in patients with tuberculosis.

Plant growth strategy determines the magnitude and direction of drought-induced changes in root exudates in subtropical forests.

Root exudates are an important pathway for plant-microbial interactions and are highly sensitive to climate change. However, how extreme drought affects root exudates and the main components, as well as species-specific differences in response magnitude and direction, are poorly understood. In this study, root exudation rates of total carbon (C) and its components (e.g., sugar, organic acid, and amino acid) were measured under the control and extreme drought treatments (i.e., 70% throughfall reduction) by in situ collection of four tree species with different growth rates in a subtropical forest. We also quantified soil properties, root morphological traits, and mycorrhizal infection rates to examine the driving factors underlying variations in root exudation. Our results showed that extreme drought significantly decreased root exudation rates of total C, sugar, and amino acid by 17.8%, 30.8%, and 35.0%, respectively, but increased root exudation rate of organic acid by 38.6%, which were largely associated with drought-induced changes in tree growth rates, root morphological traits, and mycorrhizal infection rates. Specifically, trees with relatively high growth rates were more responsive to drought for root exudation rates compared with those with relatively low growth rates, which were closely related to root morphological traits and mycorrhizal infection rates. These findings highlight the importance of plant growth strategy in mediating drought-induced changes in root exudation rates. The coordinations among root exudation rates, root morphological traits, and mycorrhizal symbioses in response to drought could be incorporated into land surface models to improve the prediction of climate change impacts on rhizosphere C dynamics in forest ecosystems.

Elevated Insulin-Like Growth Factor-1-Induced Female Rats Perpetuate the Polycystic Ovary Syndrome Phenotype: Pathological Mechanism of Insulin-Like Growth Factor-1 in Polycystic Ovary Syndrome.

OBJECTIVES: This study was designated to establish a polycystic ovary syndrome (PCOS) rat model with recombinant human insulin-like growth factor-1 (RH-IGF-1). We made assessment on the characteristics of hyperinsulinemia and hyperandrogenism in the rat model. DESIGN: This study performed the characteristics of PCOS upon RH-IGF-1 injection and evaluated the disease process of PCOS syndrome caused by the insulin-resistant pathological condition of IGF-1 based on the comparative study of in vivo test. SETTING: The experiment was conducted in the experimental research center of Yinzhou NO.2 hospital, Ningbo, Zhejiang Province, China. MATERIALS AND METHODS: Thirty-four female Sprague Dawley immature rats aged 21 days were randomly divided into two groups. Those treated with RH-IGF-1 2 mg/100 g daily were in RH-IGF-1 group (n = 20), and those with 0.9% sodium chloride 0.2 mL/100 g daily were in the saline group (n = 14). The experiment was carried out in two stages. In stage I, rats were anesthetized upon the first estrous cycle in the saline group with tissue and blood samples collected (n = 7), and rats in the RH-IGF-1-treated group were anesthetized on the 5th day after vaginal opening (VO) (n = 10). In stage II, rats in the saline group were anesthetized after three complete cycles (n = 7), meanwhile, while on the 15th day after VO (n = 10) for those in the RH-IGF-1 group. RESULTS: We have found that compared with the control group, rats injected with RH-IGF-1 expressed an early VO, disordered estrous cycle, polycystic ovaries, and significantly increased ovarian weight/body weight ratio. And from the perspective of hormone secretion, their androgen increased significantly and the insulin resistance index also elevated distinctly, possessing main characteristics similar to PCOS. LIMITATIONS: In this study, we were limited by the inability to examine IGF-1 in hypothalamus. IGF-1 in hypothalamus and in vitro experiments would be taken into consideration for further study in the future. CONCLUSIONS: These findings suggest that IGF-1 may be a key factor in the pathogenesis of PCOS, and the increase of androgen may be the pathological result, not the cause of PCOS.

Global systematic review with meta-analysis shows that warming effects on terrestrial plant biomass allocation are influenced by precipitation and mycorrhizal association.

Biomass allocation in plants is fundamental for understanding and predicting terrestrial carbon storage. Yet, our knowledge regarding warming effects on root: shoot ratio (R/S) remains limited. Here, we present a meta-analysis encompassing more than 300 studies and including angiosperms and gymnosperms as well as different biomes (cropland, desert, forest, grassland, tundra, and wetland). The meta-analysis shows that average warming of 2.50 °C (median = 2 °C) significantly increases biomass allocation to roots with a mean increase of 8.1% in R/S. Two factors associate significantly with this response to warming: mean annual precipitation and the type of mycorrhizal fungi associated with plants. Warming-induced allocation to roots is greater in drier habitats when compared to shoots (+15.1% in R/S), while lower in wetter habitats (+4.9% in R/S). This R/S pattern is more frequent in plants associated with arbuscular mycorrhizal fungi, compared to ectomycorrhizal fungi. These results show that precipitation variability and mycorrhizal association can affect terrestrial carbon dynamics by influencing biomass allocation strategies in a warmer world, suggesting that climate change could influence belowground C sequestration.

Grazing and global change factors differentially affect biodiversity-ecosystem functioning relationships in grassland ecosystems.

Grazing and global change (e.g., warming, nitrogen deposition, and altered precipitation) both contribute to biodiversity loss and alter ecosystem structure and functioning. However, how grazing and global change interactively influence plant diversity and ecosystem productivity, and their relationship remains unclear at the global scale. Here, we synthesized 73 field studies to quantify the individual and/or interactive effects of grazing and global change factors on biodiversity-productivity relationship in grasslands. Our results showed that grazing significantly reduced plant richness by 3.7% and aboveground net primary productivity (ANPP) by 29.1%, but increased belowground net primary productivity (BNPP) by 9.3%. Global change factors, however, decreased richness by 8.0% but increased ANPP and BNPP by 13.4% and 14.9%, respectively. Interestingly, the strength of the change in biodiversity in response to grazing was positively correlated with the strength of the change in BNPP. Yet, global change flipped these relationships from positive to negative even when combined with grazing. These results indicate that the impacts of global change factors are more dominant than grazing on the belowground biodiversity-productivity relationship, which is contrary to the pattern of aboveground one. Therefore, incorporating global change factors with herbivore grazing into Earth system models is necessary to accurately predict climate-grassland carbon cycle feedbacks in the Anthropocene.

UCHL1 Promoted Polarization of M1 Macrophages by Regulating the PI3K/AKT Signaling Pathway.

BACKGROUND: As deubiquitinases (DUBs), ubiquitin C-terminal hydrolase (UCH)-L1 has been shown to play a crucial role in regulating diverse biological processes. However, its function in macrophage polarization remains unclear. METHODS: We performed in vivo and in vitro experiments to investigate the role of ubiquitin carboxyl-terminal hydrolase L1 (UCHL1), a kind of DUBs, in macrophage differentiation by using UCHL1-deficiency mice. RESULTS: We demonstrated that LPS stimulation induced UCHL1 expression in macrophages. The deficiency of UCHL1 expression decreased the expression of CD80 and CD86 but increased the expression of CD206. The expression of TNF-α, IL-6, iNOS, and IL-10 was downregulated, while that of Arg1, Ym1, and Fizz1 was upregulated in UCHL1 deficient macrophages. Moreover, we observed that UCHL1 promoted the degradation of p110α through autophagy, but paradoxically increased the activity of AKT, thereby promoting polarization of macrophages into pro-inflammatory states. CONCLUSION: In this study, we identified UCHL1 as a positive regulator of M1 macrophage polarization. Our findings may help in developing therapeutic interventions for the treatment of inflammatory diseases and pathogenic infections.

Differential effects of nitrogen vs. phosphorus limitation on terrestrial carbon storage in two subtropical forests: A Bayesian approach.

Nitrogen (N) and phosphorus (P) have been demonstrated to limit terrestrial carbon (C) storage in terrestrial ecosystems. However, the reliable indicator to infer N and P limitation are still lacking, especially in subtropical forests. Here we used a terrestrial ecosystem (TECO) model framework in combination with a Bayesian approach to evaluate effects of nutrient limitation from added N/P processes and data sets on C storage capacities in two subtropical forests (Tiantong and Qianyanzhou [QYZ]). Three of the six simulation experiments were developed with assimilating data (TECO C model with C data [C-C], TECO C-N coupling model with C and N data [CN-CN], and TECO C-N-P model with C, N, and P data [CNP-CNP]), and the other three ones were simulated without assimilating data (C-only, CN-only, and CNP-only). We found that P dominantly constrained C storage capacities in Tiantong (42%) whereas N limitation decreased C storage projections in QYZ (44%). Our analysis indicated that the stoichiometry of wood biomass and soil microbe (e.g., N:P ratio) were more sensitive indicators of N or P limitation than that of other pools. Furthermore, effects of P-induced limitation were mainly on root biomass by additional P data and on both metabolic litter and soil organic carbon (SOC) by added P processes. N-induced effects were mainly from added N data that limited plant non-photosynthetic tissues (e.g., woody biomass and litter). The different effects of N and P modules on C storage projections reflected the diverse nutrient acquisition strategies associated with stand ages and plant species under nutrient stressed environment. These findings suggest that the interaction between plants and microorganisms regulate effects of nutrient availability on ecosystem C storage, and stoichiometric flexibility of N and P in plant and soil C pools could improve the representation of N and P limitation in terrestrial ecosystem models.

USP12 promotes CD4+ T cell responses through deubiquitinating and stabilizing BCL10.

Deubiquitinases (DUBs) regulate diverse biological processes and represent a novel class of drug targets. However, the biological function of only a small fraction of DUBs, especially in adaptive immune response regulation, is well-defined. In this study, we identified DUB ubiquitin-specific peptidase 12 (USP12) as a critical regulator of CD4+ T cell activation. USP12 plays an intrinsic role in promoting the CD4+ T cell phenotype, including differentiation, activation, and proliferation. Although USP12-deficient CD4+ T cells protected mice from autoimmune diseases, the immune response against bacterial infection was subdued. USP12 stabilized B cell lymphoma/leukemia 10 (BCL10) by deubiquitinating, and thereby activated the NF-κB signaling pathway. Interestingly, this USP12 regulatory mechanism was identified in CD4+ T cells, but not in CD8+ T cells. Our study results showed that USP12 activated CD4+ T cell signaling, and targeting USP12 might help develop therapeutic interventions for treating inflammatory diseases or pathogen infections.

ß-Arrestin 2 Regulates Inflammatory Responses against Mycobacterium tuberculosis Infection through ERK1/2 Signaling.

Mycobacterium tuberculosis, the pathogen that causes tuberculosis, exhibits complex host-pathogen interactions. Pattern recognition receptors and their downstream signaling pathways play crucial roles in determining the outcome of infection. In particular, the scaffold protein ß-arrestin 2 mediates downstream signaling of G protein-coupled receptors. However, the role of ß-arrestin 2 in conferring immunity against M. tuberculosis has not yet been explored. We found that ß-arrestin 2 was upregulated in the lesioned regions of lung tissues in patients with tuberculosis. M. tuberculosis infection upregulated ß-arrestin 2 expression in human macrophages, and silencing of ß-arrestin 2 significantly enhanced bactericidal activity by enhancing the expression of proinflammatory cytokines such as TNF-α. ß-Arrestin 2 was shown to inhibit the activation of the TLR2/ERK1/2 pathway and its transcriptional regulation activity upon M. tuberculosis infection. Furthermore, ß-arrestin 2 transcriptionally regulates TNF-α by binding to CREB1. These observations revealed that the upregulation of ß-arrestin 2 is critical for M. tuberculosis to escape immune surveillance through an unknown mechanism. Our research offers a novel interference modality to enhance the immune response against tuberculosis by targeting ß-arrestin 2 to modulate the TLR2-ß-arrestin 2-ERK1/2-CREB1-TNF-α regulatory axis.

Vitamin B6 prevents excessive inflammation by reducing accumulation of sphingosine-1-phosphate in a sphingosine-1-phosphate lyase-dependent manner.

Vitamin B6 is necessary to maintain normal metabolism and immune response, especially the anti-inflammatory immune response. However, the exact mechanism by which vitamin B6 plays the anti-inflammatory role is still unclear. Here, we report a novel mechanism of preventing excessive inflammation by vitamin B6 via reduction in the accumulation of sphingosine-1-phosphate (S1P) in a S1P lyase (SPL)-dependent manner in macrophages. Vitamin B6 supplementation decreased the expression of pro-inflammatory cytokines by suppressing nuclear factor-κB and mitogen-activated protein kinases signalling pathways. Furthermore, vitamin B6-reduced accumulation of S1P by promoting SPL activity. The anti-inflammatory effects of vitamin B6 were inhibited by S1P supplementation or SPL deficiency. Importantly, vitamin B6 supplementation protected mice from lethal endotoxic shock and attenuated experimental autoimmune encephalomyelitis progression. Collectively, these findings revealed a novel anti-inflammatory mechanism of vitamin B6 and provided guidance on its clinical use.

Electrochemiluminescence resonance energy transfer immunoassay for alkaline phosphatase using p-nitrophenyl phosphate as substrate.

A sensitive electrochemiluminescent immunoassay for alkaline phosphatase (ALP) using p-nitrophenyl phosphate (PNPP) as substrate based on the electrochemiluminescence resonance energy transfer (ECRET) is developed. Luminol-doped silica nanoparticles (luminol-SiNPs) are prepared by water/oil (W/O) microemulsion method. PNPP convertes to p-nitrophenol (PNP) in the presence of ALP, which results in the absorption peak shifting from 360 nm to 450 nm. Herein the spectral overlap between absorption spectrum of PNP and electrochemiluminescence (ECL) spectrum of luminol-SiNPs (425 nm) makes energy transfer occur from luminol-SiNPs to PNP. In the optimized conditions, a linear relationship was obtained using this ECRET method at the concentration of ALP from 5 to 50 U/L (r = 0.9905) and with the limit of detection (LOD) of 0.8 U/L. This ECRET method exhibits sufficient specificity for ALP over other enzymes such as horseradish peroxidase, trypsin and lysozyme.

NLRC3 expression in dendritic cells attenuates CD4+ T cell response and autoimmunity.

NOD-like receptor (NLR) family CARD domain containing 3 (NLRC3), an intracellular member of NLR family, is a negative regulator of inflammatory signaling pathways in innate and adaptive immune cells. Previous reports have shown that NLRC3 is expressed in dendritic cells (DCs). However, the role of NLRC3 in DC activation and immunogenicity is unclear. In the present study, we find that NLRC3 attenuates the antigen-presenting function of DCs and their ability to activate and polarize CD4+ T cells into Th1 and Th17 subsets. Loss of NLRC3 promotes pathogenic Th1 and Th17 responses and enhanced experimental autoimmune encephalomyelitis (EAE) development. NLRC3 negatively regulates the antigen-presenting function of DCs via p38 signaling pathway. Vaccination with NLRC3-overexpressed DCs reduces EAE progression. Our findings support that NLRC3 serves as a potential target for treating adaptive immune responses driving multiple sclerosis and other autoimmune disorders.

Electrochemiluminescence "turn-off" detection of curcumin via energy transfer using luminol-doped silica nanoparticles.

A method is presented for electrochemiluminescent (ECL) detection of the food additive curcumin via an energy transfer strategy and by using luminol-doped silica nanoparticles (luminol-NPs). The ECL emission of the luminol-NPs (peaking at 425 nm) is reduced in the presence of curcumin due to spectral overlap. The assay can be performed within 1 min, response is linear in the 0.1 to 100 µM curcumin concentration range, and the limit of detection is 32 nM. The method is selective over many ions, adenosine triphosphate, ascorbic acid, cysteine and folic acid. It was successfully applied to the determination of curcumin in spiked human serum and urine. The average recoveries range from 99.0 to 102.6%. Graphical abstract Electrochemiluminescence (ECL) "turn-off" detection of curcumin at levels as low as 32 nM via energy transfer using luminol-doped silica nanoparticles. No hydrogen peroxide (H2O2) is used in ECL detection which makes the luminol-NPs ECL system more stable than the conventional luminol-H2O2 ECL system.

IL-36γ Promotes Killing of Mycobacterium tuberculosis by Macrophages via WNT5A-Induced Noncanonical WNT Signaling.

Mycobacterium tuberculosis, which primarily infects mononuclear phagocytes, remains the leading bacterial cause of enormous morbidity and mortality because of bacterial infections in humans throughout the world. The IL-1 family of cytokines is critical for host resistance to M. tuberculosis As a newly discovered subgroup of the IL-1 family, although IL-36 cytokines have been proven to play roles in protection against M. tuberculosis infection, the antibacterial mechanisms are poorly understood. In this study, we demonstrated that IL-36γ conferred to human monocyte-derived macrophages bacterial resistance through activation of autophagy as well as induction of WNT5A, a reported downstream effector of IL-1 involved in several inflammatory diseases. Further studies showed that WNT5A could enhance autophagy of monocyte-derived macrophages by inducing cyclooxygenase-2 (COX-2) expression and in turn decrease phosphorylation of AKT/mTOR via noncanonical WNT signaling. Consistently, the underlying molecular mechanisms of IL-36γ function are also mediated by the COX-2/AKT/mTOR signaling axis. Altogether, our findings reveal a novel activity for IL-36γ as an inducer of autophagy, which represents a critical inflammatory cytokine that control the outcome of M. tuberculosis infection in human macrophages.

Effects of livestock grazing on grassland carbon storage and release override impacts associated with global climate change.

Predicting future carbon (C) dynamics in grassland ecosystems requires knowledge of how grazing and global climate change (e.g., warming, elevated CO2 , increased precipitation, drought, and N fertilization) interact to influence C storage and release. Here, we synthesized data from 223 grassland studies to quantify the individual and interactive effects of herbivores and climate change on ecosystem C pools and soil respiration (Rs). Our results showed that grazing overrode global climate change factors in regulating grassland C storage and release (i.e., Rs). Specifically, grazing significantly decreased aboveground plant C pool (APCP), belowground plant C pool (BPCP), soil C pool (SCP), and Rs by 19.1%, 6.4%, 3.1%, and 4.6%, respectively, while overall effects of all global climate change factors increased APCP, BPCP, and Rs by 6.5%, 15.3%, and 3.4% but had no significant effect on SCP. However, the combined effects of grazing with global climate change factors also significantly decreased APCP, SCP, and Rs by 4.0%, 4.7%, and 2.7%, respectively but had no effect on BPCP. Most of the interactions between grazing and global climate change factors on APCP, BPCP, SCP, and Rs were additive instead of synergistic or antagonistic. Our findings highlight the dominant effects of grazing on C storage and Rs when compared with the suite of global climate change factors. Therefore, incorporating the dominant effect of herbivore grazing into Earth System Models is necessary to accurately predict climate-grassland feedbacks in the Anthropocene.

Water-dispersed fluorescent silicon nanodots as probes for fluorometric determination of picric acid via energy transfer.

Water-dispersed fluorescent silicon nanodots (SiNDs) were synthesized by a one-pot hydrothermal method starting from tetraethyl orthosilicate (TEOS) as silicon source and trisodium citrate as reducing reagent. The method is simple and convenient. The SiNDs, with excitation/emission peaks at 347/440 nm and with fluorescence quantum yield of 18% are shown to be viable fluorescent probes for picric acid (PA). The SiNDs strongly bind PA, and their blue fluorescence is quenched. The distance between the donor and acceptor (R0 value) is calculated from fluorescence data to be 2.1 nm. A fluorometric method was worked out that has a linear response in the 8 nM to 50 µM PA concentration range and a 0.92 nM limit of detection. The method has a fast response (2 min) and is well selective over other nitroaromatic compounds and metal ions. The average recoveries from spiked lake water samples ranged between 98.4 and 100.8%. Graphical abstract Water-dispersed fluorescent silicon nanodots (SiNDs) are synthesized using tetraethyl orthosilicate (TEOS) and trisodium citrate. Based on spectral overlap of fluorescent spectrum of SiNDs and absorption spectrum of picric acid (PA), fluorometric determination of PA at concentrations as low as 0.92 nM is achieved.