TIAM2S-positive microglia enhance inflammation and neurotoxicity through soluble ICAM-1-mediated immune priming.

TIAM Rac1-associated GEF 2 short form (TIAM2S) as an oncoprotein alters the immunity of peripheral immune cells to construct an inflammatory tumor microenvironment. However, its role in the activation of microglia, the primary innate immune cells of the brain, and neuroinflammation remains unknown. This study investigated the mechanism underlying TIAM2S shapes immune properties of microglia to facilitate neuron damage. Human microglial clone 3 cell line (HMC3) and human brain samples were applied to determine the presence of TIAM2S in microglia by western blots and double immunostaining. Furthermore, TIAM2S transgenic mice combined with multiple reconstituted primary neuron-glial culture systems and a cytokine array were performed to explore how TIAM2S shaped immune priming of microglia and participated in lipopolysaccharide (LPS)-induced neuron damage. TIAM2S protein was detectable in HMC3 cells and presented in a small portion (~11.1%) of microglia in human brains referred to as TIAM2S-positive microglia. With the property of secreted soluble factor-mediated immune priming, TIAM2S-positive microglia enhanced LPS-induced neuroinflammation and neural damage in vivo and in vitro. The gain- and loss-of-function experiments showed soluble intercellular adhesion molecule-1 (sICAM-1) participated in neurotoxic immune priming of TIAM2S+ microglia. Together, this study demonstrated a novel TIAM2S-positive microglia subpopulation enhances inflammation and neurotoxicity through sICAM-1-mediated immune priming.

Insights into antibiotic resistance gene abundances and regulatory mechanisms induced by ionic liquids during composting.

This study investigated the regulatory mechanism of the evolution of antibiotic resistance genes (ARGs) during the composting process with sawdust and cow manure as raw materials using ionic liquids (ILs) pretreatment. The results showed that genes of MLS, chloramphenicol, tetracycline, beta - lactam as composting gradually decreased. From day0 to day3, MLS in control group (CK) and experimental group (T) decreased by 25.62% and 26.66%, respectively. Tetracycline decreased by 7.21% in CK and by 7.86% in T. Chloramphenicol decreased by 2.85% in CK and 3.34% in T. Beta-lactam decreased by 1.95% in Ck and by 3.69% in T. Mechanism studies have shown that ILs can effectively decompose extracellular polymeric substances (EPS) and enhance lactose dehydrogenase (LDH) release, resulting in ARGs release and elimination. Meanwhile, ILs pretreatment can inhibit growth of some ARGs hosts, especially Firmicutes, resulting in decreased ARGs. Moreover, metabolic pathways and related genes take part in ARGs transmission were down regulated, leading to decreased ARGs.

The fates of antibiotic resistance genes and their association with cell membrane permeability in response to peroxydisulfate during composting.

The aims of this study were to use metagenomics to reveal the fates of antibiotic resistance genes (ARGs) during composting under the regulation of peroxydisulfate and clarify the relationship between ARGs and cell membrane permeability. Results showed that peroxydisulfate increased cell membrane permeability by effectively regulating the expression of outer membrane protein and lipopolysaccharide related genes. Besides, it reduced polysaccharides and proteins in extracellular polymer substances by 36% and 58%, respectively, making it easier for intracellular ARGs (i-ARGs) to reach the extracellular environment, among which the absolute intracellular abundance of mphK, Erm(31), and tet(44) decreased to 1.2, 1.0, and 0.89 fold of the control, respectively. Finally, variation partitioning analysis showed that i-ARGs dominated the removal of ARGs. These results revealed that the removal of i-ARGs by activated peroxydisulfate was the key to the removal of ARGs and increased cell membrane permeability played a key role for peroxydisulfate to remove i-ARGs during composting.

The removal performances and evaluation of heavy metals, antibiotics, and resistomes driven by peroxydisulfate amendment during composting.

This study aimed to explore the effect of peroxydisulfate on the removal of heavy metals, antibiotics, heavy metal resistance genes (HMRGs), and antibiotic resistance genes (ARGs) during composting. The results showed that peroxydisulfate achieved the passivation of Fe, Mn, Zn, and Cu by promoting their speciation variations, thus reducing their bioavailability. And the residual antibiotics were better degraded by peroxydisulfate. In addition, metagenomics analysis indicated that the relative abundance of most HMRGs, ARGs, and MGEs was more effectively down-regulated by peroxydisulfate. Network analysis confirmed Thermobifida and Streptomyces were dominant potential host bacteria of HMRGs and ARGs, whose relative abundance was also effectively down-regulated by peroxydisulfate. Finally, mantel test showed the significant effect of the evolution of microbial communities and strong oxidation of peroxydisulfate on the removal of pollutants. These results suggested that heavy metals, antibiotics, HMRGs, and ARGs shared a joint fate of being removed driven by peroxydisulfate during composting.

A novel carbon-nitrogen coupled metabolic pathway promotes the recyclability of nitrogen in composting habitats.

This study revealed a novel carbon-nitrogen coupled metabolic pathway. Results showed that the addition of inorganic carbon sources slowed down the decomposition of urea and conserved more nutrients in composting. Metagenomic analysis showed that the main bacteria involved in this new pathway were Actinobacteria, Proteobacteria and Firmicutes. During the late composting period, the dominant genus Microbacteium involved in denitrification accounted for 22.18% in control (CP) and only 0.12% in treatment group (T). Moreover, ureC, rocF, argF, argI, argG were key genes involved in urea cycle. The abundance of functional gene ureC and denitrification genes decreased in thermophilic and cooling phases, respectively. The genes hao, nosZ, ureA and nifH were more closely associated with Chloroflexi_bacterium and Bacillus_paralichenformis. In conclusion, composting habitats with additional inorganic carbon sources could not only weaken denitrification but also allow more nitrogen to be conserved through slow-release urea to improve resource utilization and decrease the environmental risk.

Performances of antibiotic resistance genes profile upon the action of biochar-activated peroxydisulfate in composting.

In this study, the amendment of biochar-activated peroxydisulfate during composting to remove antibiotic resistance genes (ARGs) by direct (microbial community succession) and indirect methods (physicochemical factors) was analyzed. When implementing indirect methods, the synergistic effect of peroxydisulfate with biochar optimized the physicochemical habitat of compost, maintaining its moisture within a range of 62.95%-65.71%, and a pH of 6.87-7.73, and causing the compost to mature 18 days earlier than the control groups. The direct methods caused the optimized physicochemical habitat to adjust the microbial communities and reduce the abundance of most of the ARG host bacteria (Thermopolyspora, Thermobifida, and Saccharomonospora), thus inhibiting this substance's amplification. Heatmap analysis confirmed the necessary connection between physicochemical factors, microbial communities, and ARGs. Moreover, a mantel test confirmed the direct significant effect of the microbial communities on ARGs and the indirect significant effect of physicochemical factors on ARGs. The results showed that the abundance of more ARGs was down-regulated at the end of composting and regulated by biochar-activated peroxydisulfate, especially for the abundance of AbaF, tet(44), golS, and mryA, which was significantly decreased by 0.87-1.07 fold. These results provide new insights into the removal of ARGs during composting.

Diversity of lignocellulolytic functional genes and heterogeneity of thermophilic microbes during different wastes composting.

The goal of this study was to investigate the heterogeneity of thermophilic microorganisms and their lignocellulose-degrading gene diversity during composting. In this study, bagasse pith/dairy manure (BAG) and sawdust/dairy manure (SAW) were used as experimental subjects. The pour plate method indicated that thermophilic bacteria and thermophilic actinobacteria were more culturable than thermophilic fungi. Metagenomics analysis showed that the Actinobacteria, Firmicutes and Proteobacteria were the dominant phyla during composting. In addition, auxiliary activity and glycoside hydrolase families were critical for lignocellulosic degradation, which were found to be more abundant in BAG. As a result, the degradation rates of cellulose, hemicellulose and lignin in BAG (7.36%, 13.99% and 5.68%) were observably higher than those in SAW (6.13%, 12.09% and 2.62%). These findings contribute to understanding how thermophilic microbial communities play a role in the deconstruction of different lignocelluloses and provide a potential strategy to comprehensively utilize the resources of lignocellulosic biomass.

Metagenomic insights into role of red mud in regulating fate of compost antibiotic resistance genes mediated by both direct and indirect ways.

In this study, the amendment of red mud (RM) in dairy manure composting on the fate of antibiotic resistance genes (ARGs) by both direct (bacteria community, mobile genetic elements and quorum sensing) and indirect ways (environmental factors and antibiotics) was analyzed. The results showed that RM reduced the total relative abundances of 10 ARGs and 4 mobile genetic elements (MGEs). And the relative abundances of total ARGs and MGEs decreased by 53.48% and 22.30% in T (with RM added) on day 47 compared with day 0. Meanwhile, the modification of RM significantly increased the abundance of lsrK, pvdQ and ahlD in quorum quenching (QQ) and decreased the abundance of luxS in quorum sensing (QS) (P < 0.05), thereby attenuating the intercellular genes frequency of communication. The microbial community and network analysis showed that 25 potential hosts of ARGs were mainly related to Firmicutes, Proteobacteria and Actinobacteria. Redundancy analysis (RDA) and structural equation model (SEM) further indicated that RM altered microbial community structure by regulating antibiotic content and environmental factors (temperature, pH, moisture content and organic matter content), which then affected horizontal gene transfer (HGT) in ARGs mediated by QS and MGEs. These results provide new insights into the dissemination mechanism and removal of ARGs in composting process.

Synergistic metabolism of carbon and nitrogen: Cyanate drives nitrogen cycle to conserve nitrogen in composting system.

In this study, HCO3- was used as a co-substrate for cyanate metabolism to investigate its effect on nitrogen cycle in composting. The results showed that the carbamate content in experimental group (T) with HCO3- added was higher than that in control group (CP) during cooling period. Actinobacteria and Proteobacteria were the dominant phyla for cyanate metabolism, and the process was mediated by cyanase gene (cynS). The cynS abundance was 16.6% higher in T than CP. In cooling period, the nitrification gene hao in T was 8.125% higher than CP. Denitrification genes narG, narH, nirK, norB, and nosZ were 25.64%, 35.33%, 45.93%, 36.62%, and 36.12% less than CP, respectively. The nitrogen fixation gene nifH in T was consistently higher than CP in the late composting period. Conclusively, cyanate metabolism drove the nitrogen cycle by promoting nitrification, nitrogen fixation, and inhibiting denitrification, which improved nitrogen retention and compost quality.

Metagenomics analysis unraveled the influence of sulfate radical-mediated compost nitrogen transformation process.

The mechanism of nitrogen transformation of sulfate radical (SO- 4⋅) in the process of composting is unclear. The objectives of this study were to investigate the influence of SO- 4⋅ on nitrogen biotransformation during composting and to compare the differences in physicochemical parameters and metagenomics analysis between CK (fresh dairy manure and bagasse pith) and PS (the composting raw materials added with potassium persulfate). The results indicated that SO-4⋅ guides electron transfer in the conversion of NH+4-N to NO- 3-N and breaches the extracellular polysaccharide (EPS) structure to promote nitrogen removal. Aminomonooxygenase (AMO) and nitrate reductase (NR) levels displayed an interactive relationship between microorganisms and substrates. Metagenomics analysis revealed distinct microbial community compositions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways between nitrification and denitrification. Correlation analysis indicated that Methanobrevibacter, Bacillus and Pseudomonas were closely related to these processes. This work demonstrates the effect of SO- 4⋅ on nitrogen cycling and retention, and possible mechanisms of nitrification and denitrification during composting.

Exploring the effects of heavy metal passivation under Fenton-like reaction on the removal of antibiotic resistance genes during composting.

This study aims to explore the succession of microbes carrying antibiotic resistance genes (ARGs), the relationship between heavy metal speciation and ARGs via Fenton-like reaction during composting. The results indicated that the passivation of Cu and Ni was more prominent, and the Fenton-like reaction promoted exceptionally the passivation of Zn, Ni and Mn. The removals of macrolides-lincosamids-streptogramins (MLS), aminoglycoside and tetracycline resistance genes were induced with the composting process, but the relative abundance of bacitracin resistance genes increased. Additionally, Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes were main carriers and disseminators of ARGs, and the Fenton-like reaction improved the contribution degree of Proteobacteria to bacitracin, tetracycline and aminoglycoside resistance genes. Redundancy analysis revealed the passivation of heavy metal contributed to the removal of tetracycline, MLS and aminoglycoside resistance genes. Conclusively, the Fenton-like reaction promoted the passivation of Zn, Ni and Mn, and controlled the abundance of bacitracin resistance genes in composting.

Lignocellulosic depolymerization induced by ionic liquids regulating composting habitats based on metagenomics analysis.

The application of ionic liquids with sawdust and fresh dairy manure was studied in composting. The degradation of organic matter (OM), dissolved organic matter (DOM), and lignocellulose was analyzed. The DOM decreased by 14.25 mg/g and 11.11 mg/g in experimental group (ILs) and control group (CK), respectively. OM decreased by 7.32% (CK) and 8.91% (ILs), respectively. The degradation rates of hemicellulose, lignin, and cellulose in ILs (56.62%, 42.01%, and 23.97%) were higher than in CK (38.39%, 39.82%, and 16.04%). Microbial community and carbohydrate-active enzymes (CAZymes) were analyzed based on metagenomics. Metagenomic analysis results showed that ionic liquids enriched Actinobacteria and Proteobacteria in composting. Compared with CK, the total abundance values of GH11, GH6, AA6, and AA3_2 in ILs increased by 13.98%, 10.12%, 11.21%, and 13.68%, respectively. Ionic liquids can improve the lignocellulosic degradation by regulating the environmental physicochemical parameters (temperature, pH, C/N) to promote the growth of Actinobacteria and Proteobacteria and carbohydrate-active enzymes (CAZymes) abundance. Therefore, ionic liquids are a promising additive in lignocellulosic waste composting.

In-situ generation of H2O2 by zero valent iron to control depolymerization of lignocellulose in composting niche.

Lignocellulosic degradation is a bottleneck of bioconversion during the composting process. In-situ generation of H2O2 in the composting system was an ideal method for efficiently promoting lignocellulase degradation, and zero valent iron (ZVI) was concerned because it can generate H2O2 by reducing dissolved oxygen. This study focused on the effects of ZVI treatment on lignocellulose degradation, microbial communities, and carbohydrate-active enzymes (CAZymes) genes during composting. Its results indicated that ZVI increased H2O2 content during composting, accompanied by the formation of •OH. The degradation rates of lignin, cellulose and hemicellulose in ZVI group (20.77%, 30.35% and 44.7%) were significantly higher than in CK group (17.01%, 26.12% and 38.5%). Metagenomic analysis showed that ZVI induced microbial growth that favored lignocellulose degradation, which increased the abundance of Actinobacteria and Firmicutes but reduced Proteobacteria. At the genus level, the abundance of Thermomonospora, Streptomyces, and Bacillus significantly increased. In addition, glycoside hydrolases and auxiliary activities were important CAZymes families of lignocellulose degradation, and their abundance was higher in the ZVI group. Redundancy analysis showed that the increased H2O2 and •OH content was a critical factor in improving lignocellulose degradation. Overall, H2O2 as a co-substrate enhanced the enzymatic efficiency, •OH unspecifically attacked lignocellulose, and the increase in functional microbial abundance was the main reason for promoting lignocellulose degradation in composting.

Signature of dissolved organic matter and microbial communities based on different oxygen levels response during distillers dried grains with solubles plus sugarcane pith co-fermentations.

The objective of this study was to investigate the relationship between dissolved organic matter (DOM) and microbial communities during the co-fermentation of distillers dried grains with solubles (DDGS) and sugarcane pith at different oxygen levels. In aerobic fermentation (AF), the content of DOM decreased from 32.61 mg/g to 14.14 mg/g, and decreased from 32.61 mg/g to 30.83 mg/g in anaerobic fermentation (ANF). Phenols and alcohols were consumed first in AF, while lipids and proteins were consumed first in ANF. Degradation rates of cellulose, hemicellulose and lignin in AF (6.67%, 39.93%, 36.50%) were higher than those in ANF (0.69%, 18.36%, 9.12%). Firmicutes, Actinobacteriota and Ascomycota were the main phyla in community. Distance-based redundancy analysis showed that pH, organic matter (OM) and DOM were the main driving factors of microbial community succession.

Biochar-based solid acid accelerated carbon conversion by increasing the abundance of thermophilic bacteria in the cow manure composting process.

This study investigated the effects of biochar-based solid acids (SAs) on carbon conversion, alpha diversity and bacterial community succession during cow manure composting with the goal of providing a new strategy for rapid carbon conversion during composting. The addition of SA prolonged the thermophilic phase and accelerated the degradation of lignocellulose; in particular, the degradation time of cellulose was shortened by 50% and the humus content was increased by 22.56% compared with the control group (CK). In addition, high-throughput sequencing results showed that SA improved the alpha diversity and the relative abundance of thermophilic bacteria, mainly Actinobacteria, increased by 12.955% compared with CK. A redundancy analysis (RDA) showed that Actinobacteria was positively correlated with the transformation of carbon.

Red mud conserved compost nitrogen by enhancing nitrogen fixation and inhibiting denitrification revealed via metagenomic analysis.

The objective of this study was to investigate the effects of adding red mud (RM) on denitrification and nitrogen fixation in composting. The results revealed that the retentions of NH4+-N and NO3--N in experimental group (T) with RM were 16.20% and 7.27% higher than that in control group (CK) at the mature stage, respectively. The composition and structure of RM can effectively inhibit denitrification and enhance nitrogen fixation. Moreover, metagenomic analysis revealed that Actinobacteria and Proteobacteria were the main microorganisms in denitrification process, while Firmicutes were the main microorganisms in nitrogen fixation process. In T, denitrifying genes nirK and nosZ were 11% and 18% lower than those in CK, respectively, while nitrogen-fixing genes nifK and nifD were 18% and 34% higher than those in control group, respectively. Therefore, adding RM could reduce nitrogen loss and improve the quality of compost via enhancing nitrogen fixation and inhibiting denitrification process.

Immune Checkpoint Inhibitor-Induced Myasthenia Gravis.

The development of immune checkpoint inhibitors (ICIs) has been a major breakthrough in cancer immunotherapy. The increasing use of ICIs has led to the discovery of a broad spectrum of immune-related adverse events (irAEs). Immune-related myasthenia gravis (irMG) is a rare but life-threatening irAE. In this review, the clinical presentations of irMG are described and the risk of irMG-related mortality is examined using information from relevant studies. In 47 reported cases of irMG with clear causes of mortality, irMG appeared to be a distinct category of neuromuscular disorders and differed from classical MG in terms of its demographic patient characteristics, pathogenesis, serology profile, response to treatment, associated complications, and prognosis. Because of the high mortality of irMG, measures to increase the vigilance of medical teams are necessary to ensure the timely identification of the signs of irMG and early treatment, particularly in the early course of ICI therapy. The diagnostic plans should be comprehensive and include the evaluation of other organ systems, such as the dermatological, gastrointestinal, respiratory, neuromuscular, and cardiovascular systems, in addition to the traditional diagnostic tests for MG. Treatment plans should be individualized on the basis of the extent of organ involvement and clinical severity. Additional therapeutic studies on irMG in the future are required to minimize irAE-related mortality and increase the safety of patients with cancer in the ICI era.