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While originally identified as an antiviral pathway, recent work has implicated that cyclic GMP-AMP-synthase-Stimulator of Interferon Genes (cGAS-STING) signaling is playing a critical role in the neuroinflammatory response to traumatic brain injury (TBI). STING activation results in a robust inflammatory response characterized by the production of inflammatory cytokines called interferons, as well as hundreds of interferon stimulated genes (ISGs). Global knock-out (KO) mice inhibiting this pathway display neuroprotection with evidence that this pathway is active days after injury; yet, the early neuroinflammatory events stimulated by STING signaling remain understudied. Furthermore, the source of STING signaling during brain injury is unknown. Using a murine controlled cortical impact (CCI) model of TBI, we investigated the peripheral immune and microglial response to injury utilizing male chimeric and conditional STING KO animals, respectively. We demonstrate that peripheral and microglial STING signaling contribute to negative outcomes in cortical lesion volume, cell death, and functional outcomes postinjury. A reduction in overall peripheral immune cell and neutrophil infiltration at the injury site is STING dependent in these models at 24â h. Transcriptomic analysis at 2â h, when STING is active, reveals that microglia drive an early, distinct transcriptional program to elicit proinflammatory genes including interleukin 1-ß (IL-1ß), which is lost in conditional knock-out mice. The upregulation of alternative innate immune pathways also occurs after injury in these animals, which supports a complex relationship between brain-resident and peripheral immune cells to coordinate the proinflammatory response and immune cell influx to damaged tissue after injury.
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Lesões Encefálicas Traumáticas , Microglia , Animais , Masculino , Camundongos , Lesões Encefálicas Traumáticas/patologia , Citocinas/metabolismo , Interferons/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microglia/metabolismo , Transdução de SinaisRESUMO
Monocytes represent key cellular elements that contribute to the neurological sequela following brain injury. The current study reveals that trauma induces the augmented release of a transcriptionally distinct CD115+/Ly6Chi monocyte population into the circulation of mice pre-exposed to clodronate depletion conditions. This phenomenon correlates with tissue protection, blood-brain barrier stability, and cerebral blood flow improvement. Uniquely, this shifted the innate immune cell profile in the cortical milieu and reduced the expression of pro-inflammatory Il6, IL1r1, MCP-1, Cxcl1, and Ccl3 cytokines. Monocytes that emerged under these conditions displayed a morphological and gene profile consistent with a subset commonly seen during emergency monopoiesis. Single-cell RNA sequencing delineated distinct clusters of monocytes and revealed a key transcriptional signature of Ly6Chi monocytes enriched for Apoe and chitinase-like protein 3 (Chil3/Ym1), commonly expressed in pro-resolving immunoregulatory monocytes, as well as granule genes Elane, Prtn3, MPO, and Ctsg unique to neutrophil-like monocytes. The predominate shift in cell clusters included subsets with low expression of transcription factors involved in monocyte conversion, Pou2f2, Na4a1, and a robust enrichment of genes in the oxidative phosphorylation pathway which favors an anti-inflammatory phenotype. Transfer of this monocyte assemblage into brain-injured recipient mice demonstrated their direct role in neuroprotection. These findings reveal a multifaceted innate immune response to brain injury and suggest targeting surrogate monocyte subsets may foster tissue protection in the brain.
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Lesões Encefálicas , Monócitos , Camundongos , Animais , Monócitos/metabolismo , Neutrófilos/metabolismo , Lesões Encefálicas/metabolismo , Encéfalo/metabolismo , Perfilação da Expressão Gênica , Catepsina G/metabolismoRESUMO
Objective: Inconsistent evidence exists regarding the association between intraoperative hypothermia and incidence of surgical site infection (SSI). This study aimed to determine the association between intraoperative hypothermia and SSI. Materials and methods: A systematic review was conducted using Embase, PubMed, and Web of Science to identify observational studies evaluating the risk of SSI in patients with intraoperative hypothermia. The primary outcome measure was the diagnosis of SSI within 30 days of surgery. The pooled risk ratio was estimated using a fixed- or random-effect meta-analysis. Sensitivity analyses were performed to examine the impact of the structural design of preoperative warming on the pooled risk of SSI. Results: Five studies representing 6,002 patients were included in the present meta-analysis. Intraoperative hypothermia was not associated with SSI risk in patients (HR = 1.22, 95% CI: 0.95-2.24, P = 0.119). The pooled hazard ratio showed that intraoperative hypothermia did not result in a higher risk of SSI. Conclusions: Intraoperative hypothermia was not associated with the risk of SSI. Further studies using objective exposure measurements are required to confirm these results.
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Tetracycline is an antibiotic with extensive veterinary use in the livestock industry. However, their widespread application poses risks to soil health as residue in livestock feces, and their removal is crucial for sustainable soil-ecosystem development. Physical and chemical approaches to extract tetracycline may have adverse effects on soil ecosystems, but no studies have thus far examined the potential for biological methods, such as collective degradation action of soil fauna. Thus, this study aimed to investigate the synergistic effects of lactic acid bacteria (LAB) and earthworms (Eisenia fetida) on biodegradation of tetracycline residues in sheep manure. We assessed earthworm biomass, tetracycline residue, and bacterial communities in both earthworm intestines and vermicompost. Earthworm biomass and tetracycline degradation efficiency increased significantly with LAB addition, with a degradation rate of up to 80.16%. This increase may be attributable to LAB acting as electron donors to spur tetracycline degradation. Additionally, we noted that tetracycline presence significantly influenced bacterial communities in earthworm intestines and vermicompost, elevating the abundance of potential pathogenic bacteria (e.g., Flavobacterium, Gammaproteobacteria, and Enterobacteriaceae). This finding suggests that heightened environmental stress from antibiotics could actually facilitate the growth of less prevalent bacteria, including potential pathogens. In conclusion, our study provides evidence supporting the effectiveness of LAB and earthworms in degrading tetracycline residues. In particular, LAB appears to mitigate stress from tetracycline exposure in earthworms, thus increasing their vermicomposting efficacy. Our work has important implications for soil management, with the potential to enhance pollution clean-up rates while minimizing negative side-effects to soil microbial communities.
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Biodegradação Ambiental , Lactobacillales , Gado , Esterco , Oligoquetos , Tetraciclina , Oligoquetos/metabolismo , Animais , Esterco/microbiologia , Lactobacillales/metabolismo , Ovinos , Poluentes do Solo/metabolismo , Poluentes do Solo/análise , Antibacterianos , Microbiologia do SoloRESUMO
NaYF4 systems have been widely studied as up-conversion host matrices, and their phase transitions are flexible and worth investigating in great detail. Herein, the evolution of morphology and crystal structure of a Eu3+-doped ß-NaYF4 single nanoparticle heated in an air atmosphere was investigated using in situ transmission electron microscopy (TEM). The annealing process revealed that the hexagonal ß-NaYF4 phase undergoes sequential transformations into high-temperature cubic phases at both 350 °C and 500 °C. The emission characteristics of Eu3+ in the single nanoparticle after heating treatment were also analyzed using Correlative Cathodoluminescence Electron Microscopy (CCLEM). The results of CCLEM suggest a gradual decrease followed by a subsequent increase in structural symmetry. A comprehensive spectroscopic and structural analysis encapsulates the entire transformation process as NaYF4 â YOF â Y2O3. In situ energy dispersive spectroscopy analyses (EDS) support this reaction process. The aforementioned technique yields correlative lattice-resolved TEM images and nanoscale spectroscopic information, which can be employed to assess the structure-function relationships on the nanoscale.
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Identifying the origins and contributions of different immune cell populations following brain injury is crucial for understanding their roles in inflammation and tissue repair. This study investigated the infiltration and phenotypic characteristics of skull bone marrow-derived immune cells in the murine brain after TBI. We performed calvarium transplantation from GFP donor mice and subjected the recipients to controlled cortical impact (CCI) injury 14 days post-transplant. Confocal imaging at 3 days post-CCI revealed GFP+ calvarium-derived cells infiltrating the ipsilateral core lesional area, expressing CD45 and CD11b immune markers. These cells included neutrophil (Ly6G+) and monocyte (Ccr2+) identities. Calvarium-derived GFP+/Iba1+ monocyte/macrophages expressed the efferocytosis receptor MerTK and displayed engulfment of NeuN+ and caspase 3+ apoptotic cells. Phenotypic analysis showed that greater calvarium-derived monocyte/macrophages disproportionately express the anti-inflammatory arginase-1 marker than pro-inflammatory CD86. To differentiate the responses of blood- and calvarium-derived macrophages, we transplanted GFP calvarium skull bone into tdTomato bone marrow chimeric mice, then performed CCI injury 14 days post-transplant. Calvarium-derived GFP+ cells predominantly infiltrated the lesion boundary, while blood-derived TdTomato+ cells dispersed throughout the lesion and peri-lesion. Compared to calvarium-derived cells, more blood-derived cells expressed pro-inflammatory CD86 and displayed altered 3D morphologic traits. These findings uniquely demonstrate that skull bone-derived immune cells infiltrate the brain after injury and contribute to the neuroinflammatory milieu, representing a novel immune cell source that may be further investigated for their causal role in functional outcomes.
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This study investigated the combined effects of rockwool, a novel seedling substrate, and tricyclazole (TCA) on the bioavailability of TCA to Eisenia fetida. The single addition of rockwool and TCA alone to the soil inhibited the growth of E. fetida. A high concentration (300 mg·L-1) of TCA significantly decreased the biomass of E. fetida. The addition of 20-mesh rockwool reduced this effect on earthworm biomass by decreasing the soil TCA through adsorption, effectively mitigating TCA bioaccumulation in earthworms. A mechanistic analysis showed that the Mg-O functional group on the rockwool surface combined with the CC functional group in TCA to generate Mg-O-C, and the adsorption process was dominated by chemisorption. Toxicology experiments demonstrated that malondialdehyde and cellulase could be used as biomarkers of inhibitory effects of combined rockwool and TCA in soil on E. fetida. Macrogenomic analyses revealed that small particle sizes and high concentrations of rockwool caused co-stress effects on earthworms when TCA was present. When the particle size of rockwool increased, the toxic effect of TCA on earthworms instead decreased at higher rockwool concentrations. Therefore, in practical agricultural production, the particle size of rockwool can be controlled to realize the adsorption of TCA and reduce the toxic effects of TCA and rockwool on earthworms.
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Oligoquetos , Poluentes do Solo , Solo , Oligoquetos/efeitos dos fármacos , Oligoquetos/metabolismo , Animais , Poluentes do Solo/toxicidade , Poluentes do Solo/metabolismo , Solo/química , Tiazóis/toxicidade , Adsorção , BiomassaRESUMO
Introduction: The panicle fertilization strategy for japonica and indica rice under wheat straw return (SR) has not been updated, especially on the elaboration of their impacts on spikelet differentiation and degeneration. This study aimed to verify the hypothesis that SR increases spikelet number by reducing spikelet degeneration and to explore the possibility of simplifying panicle fertilization. Methods: In three consecutive years, four varieties of japonica and indica rice were field-grown in Yangzhou, Jiangsu Province, China. Six panicle fertilization rates and split treatments were applied to SR and no straw return (NR) conditions. Results: The results showed that SR promoted rice yield significantly by 3.77%, and the highest yields were obtained under the T2 (split panicle fertilization at the panicle initiation (PI) and spikelet primordium differentiation (SPD) stages) and T1 (panicle fertilization only at the PI stage) treatments, for indica and japonica rice, respectively. Correlation and path analysis revealed that the number of spikelets per panicle was the most attributable to yield variation. SR significantly increased the concentration of alkali hydrolyzable N in the soil 40 days after rice transplantation, significantly increased the nitrogen accumulation per stem (NA) during the SPD-pollen mother cell meiosis (PMC) stage, and increased the brassinosteroids level in the young panicles at the PMC stage. SR also reduced the degeneration rate of spikelets (DRS) and increased the number of surviving spikelets (NSS). The dry matter accumulation per stem was more important to increasing the NA in japonica rice at the PMC stage, whereas NA was more affected by the N content than the dry matter accumulation in indica rice. In japonica rice, panicle N application once only at the PI stage combined with the N released from SR was enough to improve the plant N content, reduce the DRS, and increase the NSS. For indica rice, split application of N panicle fertilization at both the PI and SPD stages was still necessary to achieve a maximum NSS. Discussion: In conclusion, under wheat SR practice, panicle fertilization could be simplified to once in japonica rice with a significant yield increase, whereas equal splits might still be optimal for indica rice.
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BACKGROUND: The gut mycobiome is closely linked to health and disease; however, its role in the progression of type 2 diabetes mellitus (T2DM) remains obscure. Here, a multi-omics approach was employed to explore the role of intestinal fungi in the deterioration of glycemic control. METHODS: 350 participants without hypoglycemic therapies were invited for a standard oral glucose tolerance test to determine their status of glycemic control. The gut mycobiome was identified through internal transcribed spacer sequencing, host genetics were determined by genotyping array, and plasma metabolites were measured with untargeted liquid chromatography mass spectrometry. FINDINGS: The richness of fungi was higher, whereas its dissimilarity was markedly lower, in participants with T2DM. Moreover, the diversity and composition of fungi were closely associated with insulin sensitivity and pancreatic ß-cell functions. With the exacerbation of glycemic control, the co-occurrence network among fungus taxa became increasingly complex, and the complexity of the interaction network was inversely associated with insulin sensitivity. Mendelian randomization analysis further demonstrated that the Archaeorhizomycetes class, Fusarium genus, and Neoascochyta genus were causally linked to impaired glucose metabolism. Furthermore, integrative analysis with metabolomics showed that increased 4-hydroxy-2-oxoglutaric acid, ketoleucine, lysophosphatidylcholine (20:3/0:0), and N-lactoyl-phenylalanine, but decreased lysophosphatidylcholine (O-18:2), functioned as key molecules linking the adverse effect of Fusarium genus on insulin sensitivity. CONCLUSIONS: Our study uncovers a strong association between disturbance in gut fungi and the progression of T2DM and highlights the potential of targeting the gut mycobiome for the management of T2DM. FUNDINGS: This study was supported by MOST and NSFC of China.
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Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Controle Glicêmico , Micobioma , Humanos , Diabetes Mellitus Tipo 2/microbiologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/sangue , Pessoa de Meia-Idade , Masculino , Feminino , Microbioma Gastrointestinal/fisiologia , Teste de Tolerância a Glucose , Resistência à Insulina , Fusarium/genética , Fungos/genética , Adulto , Glicemia/metabolismo , Idoso , Ascomicetos/genética , MetabolômicaRESUMO
Objective To explore the effect of meteorological factors on the incidence of hand foot and mouth disease (HFMD) in Jiangyin City. Methods The distributed lag non-linear model (DLNM) was used to estimate the delayed and cumulative effects of meteorological factors on incidence of HFMD in Jiangyin from 2012 to 2017. Results A total of 21 791 HFMD cases were reported in Jiangyin City during 2012-2017. We observed significant correlations between the daily incidence of HFMD and daily mean temperature (rs=0.402, P<0.001), daily mean pressure (rs=-0.453, P<0.001), and daily mean relative humidity (rs=0.075, P<0.001), respectively. It was indicated that the maximum cumulative effect of daily mean temperature on the incidence of HFMD was 11 ℃ (RR=1.473, 95% CI: 1.99-1.974), and the impact on the onset of HFMD was acute and hightest at the first day (RR=1.090, 95% CI: 1.045-1.136). The cumulative effect on incidence of HFMD was highest at 85% daily relative humidity (RR=1.346, 95% CI: 1.154-1.571), and the impact on HFMD peaked on the 6th day (RR=1.023,95% CI: 1.015-1.031); The maximum cumulative effect of daily mean pressure with the incidence of HFMD was 1010.0 hpa (RR=1.221, 95% CI: 1.020-1.463), but no lag effect was observed at this level. Conclusions Meteorological factors have significant impact on the incidence of HFMD in Jiangyin City, and the effects of temperature and humidity are lagged.
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AIM: To investigate the efficacy of anti - vascular endothelial growth factor ( VEGF) drugs in the treatment of choroidal neovascularization ( CNV ) and its effects on intraocular pressure, best corrected visual acuity ( BCVA) and multifocal electroretinogram ( mfERG) .?METHODS:Totally 44 cases (44 eyes) of idiopathic CNV patients treated in our hospital from February 2015 to January 2017 were selected. All patients were treated with intravitreal injection of anti - VEGF. BCVA, intraocular pressure, mfERG and central retinal thickness ( CRT) were observed after treatment.?RESULTS:At 1 and 3mo after treatment, BCVA and CRT were significantly improved than those before treatment (P<0. 05). At 3mo after treatment BCVA and CRT were 0. 60±0. 15 and 278. 43±40. 10μm, both significantly lower than that in 1mo after treatment (P<0. 05). There was no significant change in intraocular pressure at 1 or 3mo after treatment than before treatment (P>0. 05). At 1 and 3mo after treatment, amplitudes of Ring1, Ring2 and Ring4 NI-P1 were higher than those before treatment (P<0. 05);at 3mo after treatment, the amplitude of Ring3 NI-P1 were higher than those before and 1mo after treatment (P<0. 05);at 1mo after treatment, the amplitude of Ring5 NI- P1 were higher than those before and 3mo after treatment (P<0. 05). The amplitude of Ring6 NI-P1 did not change significantly at 1 and 3mo after treatment, compared with before treatment (P>0. 05).?CONCLUSION: Anti-VEGF drugs are effective in the treatment of idiopathic CNV, which can improve vision and macular retinal function, decrease the retinal thickness, and do not affect the intraocular pressure.