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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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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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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
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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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
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
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
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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The development of facile methods for constructing highly active, cost-effective catalysts that meet ampere-level current density and durability requirements for an oxygen evolution reaction is crucial. Herein, a general topochemical transformation strategy is posited: M-Co9S8 single-atom catalysts (SACs) are directly converted into M-CoOOH-TT (M = W, Mo, Mn, V) pair-sites catalysts under the role of incorporating of atomically dispersed high-valence metals modulators through potential cycling. Furthermore, in situ X-ray absorption fine structure spectroscopy is used to track the dynamic topochemical transformation process at the atomic level. The W-Co9S8 breaks through the low overpotential of 160 mV at 10 mA cm-2. A series of pair-site catalysts exhibit a large current density of approaching 1760 mA cm-2 at 1.68 V vs reversible hydrogen electrode (RHE) in alkaline water oxidation and achieve a ≈240-fold enhancement in the normalized intrinsic activity compare to that reported CoOOH, and sustainable stability of 1000 h. Moreover, the OâO bond formation is confirmed via a two-site mechanism, supported by in situ synchrotron radiation infrared and density functional theory (DFT) simulations, which breaks the limit of adsorption-energy scaling relationship on conventional single-site.
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Introduction: Patients with primary adrenal insufficiency (PAI) suffer from increased risk of infection, adrenal crises and have a higher mortality rate. Such dismal outcomes have been inferred to immune cell dysregulation because of unphysiological cortisol replacement. As the immune landscape of patients with different types of PAI has not been systematically explored, we set out to immunophenotype PAI patients with different causes of glucocorticoid (GC) deficiency. Methods: This cross-sectional single center study includes 28 patients with congenital adrenal hyperplasia (CAH), 27 after bilateral adrenalectomy due to Cushing's syndrome (BADx), 21 with Addison's disease (AD) and 52 healthy controls. All patients with PAI were on a stable GC replacement regimen with a median dose of 25 mg hydrocortisone per day. Peripheral blood mononuclear cells were isolated from heparinized blood samples. Immune cell subsets were analyzed using multicolor flow cytometry after four-hour stimulation with phorbol myristate acetate and ionomycin. Natural killer (NK-) cell cytotoxicity and clock gene expression were investigated. Results: The percentage of T helper cell subsets was downregulated in AD patients (Th1 p = 0.0024, Th2 p = 0.0157, Th17 p < 0.0001) compared to controls. Cytotoxic T cell subsets were reduced in AD (Tc1 p = 0.0075, Tc2 p = 0.0154) and CAH patients (Tc1 p = 0.0055, Tc2 p = 0.0012) compared to controls. NKCC was reduced in all subsets of PAI patients, with smallest changes in CAH. Degranulation marker CD107a expression was upregulated in BADx and AD, not in CAH patients compared to controls (BADx p < 0.0001; AD p = 0.0002). In contrast to NK cell activating receptors, NK cell inhibiting receptor CD94 was upregulated in BADx and AD, but not in CAH patients (p < 0.0001). Although modulation in clock gene expression could be confirmed in our patient subgroups, major interindividual-intergroup dissimilarities were not detected. Discussion: In patients with different etiologies of PAI, distinct differences in T and NK cell-phenotypes became apparent despite the use of same GC preparation and dose. Our results highlight unsuspected differences in immune cell composition and function in PAI patients of different causes and suggest disease-specific alterations that might necessitate disease-specific treatment.
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Doença de Addison , Hiperplasia Suprarrenal Congênita , Insuficiência Adrenal , Síndrome de Cushing , Humanos , Doença de Addison/tratamento farmacológico , Estudos Transversais , Leucócitos Mononucleares/metabolismo , Síndrome de Cushing/tratamento farmacológico , Glucocorticoides/efeitos adversos , Hidrocortisona/uso terapêutico , Hiperplasia Suprarrenal Congênita/induzido quimicamente , Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Hiperplasia Suprarrenal Congênita/metabolismo , Insuficiência Adrenal/induzido quimicamente , Insuficiência Adrenal/tratamento farmacológicoRESUMO
BACKGROUND: Efferocytosis is a process that removes apoptotic cells and cellular debris. Clearance of these cells alleviates neuroinflammation, prevents the release of inflammatory molecules, and promotes the production of anti-inflammatory cytokines to help maintain tissue homeostasis. The underlying mechanisms by which this occurs in the brain after injury remain ill-defined. METHODS: We used GFP bone marrow chimeric knockout (KO) mice to demonstrate that the axon guidance molecule EphA4 receptor tyrosine kinase is involved in suppressing MERTK in the brain to restrict efferocytosis of resident microglia and peripheral-derived monocyte/macrophages. RESULTS: Single-cell RNAseq identified MERTK expression, the primary receptor involved in efferocytosis, on monocytes, microglia, and a subset of astrocytes in the damaged cortex following brain injury. Loss of EphA4 on infiltrating GFP-expressing immune cells improved functional outcome concomitant with enhanced efferocytosis and overall protein expression of p-MERTK, p-ERK, and p-Stat6. The percentage of GFP+ monocyte/macrophages and resident microglia engulfing NeuN+ or TUNEL+ cells was significantly higher in KO chimeric mice. Importantly, mRNA expression of Mertk and its cognate ligand Gas6 was significantly elevated in these mice compared to the wild-type. Analysis of cell-specific expression showed that p-ERK and p-Stat6 co-localized with MERTK-expressing GFP + cells in the peri-lesional area of the cortex following brain injury. Using an in vitro efferocytosis assay, co-culturing pHrodo-labeled apoptotic Jurkat cells and bone marrow (BM)-derived macrophages, we demonstrate that efferocytosis efficiency and mRNA expression of Mertk and Gas6 was enhanced in the absence of EphA4. Selective inhibitors of ERK and Stat6 attenuated this effect, confirming that EphA4 suppresses monocyte/macrophage efferocytosis via inhibition of the ERK/Stat6 pathway. CONCLUSIONS: Our findings implicate the ERK/Stat6/MERTK axis as a novel regulator of apoptotic debris clearance in brain injury that is restricted by peripheral myeloid-derived EphA4 to prevent the resolution of inflammation.
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Orientação de Axônios , Lesões Encefálicas , Camundongos , Animais , c-Mer Tirosina Quinase/metabolismo , Apoptose , Fagocitose/fisiologia , Camundongos Knockout , RNA Mensageiro , Fator de Transcrição STAT6/metabolismoRESUMO
BACKGROUND: Cervical spondylotic radiculopathy is a serious and common degenerative disease of the cervical spine due to irritation and compression of the nerve roots of the cervical spine, resulting in a series of clinical symptoms based on sensory, motor and reflex disorders, such as numbness and pain in the neck, shoulders, upper limbs and fingers. Acupuncture is highly effective in treating CSR and has become a common treatment accepted by patients. This study aims to systematically review and analyze existing randomized controlled trials (RCTs) to evaluate the efficacy and safety of acupuncture in the treatment of CSR. METHODS: We used the following eight databases for literature data search: PubMed, EMBASE, The Cochrane Library, Web of Science, China National Knowledge Infrastructure, China Biology Medicine Disc ( CBMdisc), Wanfang Database and China Science and Technology Journal Database (VIP). The search consisted of randomized controlled studies of acupuncture for CSR between 2000 and 2020 and the methodological quality of the included studies was assessed according to the Cochrane Collaboration's "Risk of Bias Assessment Tool."RevMan 5.4 software was used for statistical analysis only. Study screening, data extraction and statistics, and assessment of the risk of bias of the included studies were performed independently by two reviewers. RESULT: 27 studies with 3124 patients were included. The results of the meta-analysis of the total efficiency index for acupuncture for CSR were [RR = 1.14,95% CI (1.09,1.19)]. The results of the meta-analysis of the PPI index were [MD = -0.35, 95% CI (-0.61,-0. 09)]. The results of META analysis of the total effective rate, VAS score, PRI(A) score, PRI(S) score and PRI(T) score showed heterogeneity in the studies included for each outcome index, and sources of heterogeneity were sought through subgroup analysis and sensitivity analysis to ensure more stable and reliable data results. The results of the combined meta-analysis showed that the treatment group was significantly more effective than the control group and more effective in lowering the nerves to reduce the pain index in patients with CSR, with a statistically significant difference (P<0.05). This indicates that acupuncture treatment is superior to traction for CSR. CONCLUSION: Acupuncture is significantly more effective than traction therapy in the treatment of cervical spondylosis and can reduce the pain index of patients with CSR.
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Neurobiological consequences of traumatic brain injury (TBI) result from a complex interplay of secondary injury responses and sequela that mediates chronic disability. Endothelial cells are important regulators of the cerebrovascular response to TBI. Our work demonstrates that genetic deletion of endothelial cell (EC)-specific EPH receptor A4 (EphA4) using conditional EphA4f/f/Tie2-Cre and EphA4f/f/VE-Cadherin-CreERT2 knockout (KO) mice promotes blood-brain barrier (BBB) integrity and tissue protection, which correlates with improved motor function and cerebral blood flow recovery following controlled cortical impact (CCI) injury. scRNAseq of capillary-derived KO ECs showed increased differential gene expression of BBB-related junctional and actin cytoskeletal regulators, namely, A-kinase anchor protein 12, Akap12, whose presence at Tie2 clustering domains is enhanced in KO microvessels. Transcript and protein analysis of CCI-injured whole cortical tissue or cortical-derived ECs suggests that EphA4 limits the expression of Cldn5, Akt, and Akap12 and promotes Ang2. Blocking Tie2 using sTie2-Fc attenuated protection and reversed Akap12 mRNA and protein levels cortical-derived ECs. Direct stimulation of Tie2 using Vasculotide, angiopoietin-1 memetic peptide, phenocopied the neuroprotection. Finally, we report a noteworthy rise in soluble Ang2 in the sera of individuals with acute TBI, highlighting its promising role as a vascular biomarker for early detection of BBB disruption. These findings describe a contribution of the axon guidance molecule, EphA4, in mediating TBI microvascular dysfunction through negative regulation of Tie2/Akap12 signaling.
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Barreira Hematoencefálica , Lesões Encefálicas Traumáticas , Receptor EphA4 , Animais , Camundongos , Proteínas de Ancoragem à Quinase A/genética , Proteínas de Ancoragem à Quinase A/metabolismo , Barreira Hematoencefálica/metabolismo , Lesões Encefálicas Traumáticas/genética , Lesões Encefálicas Traumáticas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Células Endoteliais/metabolismo , Camundongos Knockout , Receptor TIE-2/genética , Receptor TIE-2/metabolismo , Receptor EphA4/genética , Receptor EphA4/metabolismoRESUMO
Background: Efferocytosis is a process that removes apoptotic cells and cellular debris. Clearance of these cells alleviates neuroinflammation and prevents the release of inflammatory molecules and promotes the production of anti-inflammatory cytokines to help maintain tissue homeostasis. The underlying mechanisms by which this occurs in the brain after injury remains ill-defined. Methods: We demonstrate using GFP bone marrow chimeric knockout (KO) mice, that the axon guidance molecule EphA4 receptor tyrosine kinase is involved in suppressing Mertk signaling in the brain to restrict the function of efferocytosis on resident microglia and peripheral-derived monocyte/macrophages. Results: Single-cell RNAseq identified Mertk expression, the primary receptor involved in efferocytosis, on monocytes, microglia, and a subset of astrocytes in the damaged cortex following brain injury. Loss of EphA4 on infiltrating GFP-expressing immune cells improved functional outcome concomitant with enhanced efferocytosis, and overall protein expression of p-Mertk, p-ERK, and p-Stat6. The percentage of GFP+ monocyte/macrophages and resident microglia engulfing NeuN+ or TUNEL+ cells was significantly higher in KO chimeric mice. Importantly, mRNA expression of Mertk and its cognate ligand Gas6 was significantly elevated in these mice compared to wild-type. Analysis of cell-specific expression showed that p-ERK and p-Stat6 co-localized with Mertk-expressing GFP + cells in the peri-lesional area of the cortex following brain injury. Using an in vitro efferocytosis assay, co-culturing pHrodo-labeled apoptotic Jurkat cells and bone marrow (BM)-derived macrophages, we demonstrate that efferocytosis efficiency and mRNA expression of Mertk and Gas6 was enhanced in the absence of EphA4. Select inhibitors of ERK and Stat6 attenuated this effect confirming that EphA4 suppresses monocyte/macrophage efferocytosis via inhibition of the ERK/Stat6 pathway. Conclusions: Our findings implicate the Mertk/ERK/Stat6 axis as a novel regulator of apoptotic debris clearance in brain injury that is restricted by peripheral myeloid-derived EphA4 to prevent the resolution of inflammation.
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Soil heavy metal pollution has become one of the major environmental issues of global concern and solving this problem is a major scientific and technological need for today's socio-economic development. Environmentally friendly bioremediation methods are currently the most commonly used for soil heavy metal pollution remediation. Via controlled experiments, the removal characteristics of chromium from contaminated soil were studied using earthworms (Eisenia fetida and Pheretima guillelmi) and plants (ryegrass and maize) at different chromium concentrations (15 mg/kg and 50 mg/kg) in acidic and alkaline soils. The effects of chromium contamination on biomass, chromium bioaccumulation, and earthworm gut microbial communities were also analyzed. The results showed that E. fetida had a relatively stronger ability to remove chromium from acidic and alkaline soil than P. guillelmi, and ryegrass had a significantly better ability to remove chromium from acidic and alkaline soil than maize. The combined use of E. fetida and ryegrass showed the best effect of removing chromium from contaminated soils, wih the highest removal rate (63.23%) in acidic soil at low Cr concentrations. After soil ingestion by earthworms, the content of stable chromium (residual and oxidizable forms) in the soil decreased significantly, while the content of active chromium (acid-extractable and reducible forms) increased significantly, thus promoting the enrichment of chromium in plants. The diversity in gut bacterial communities in earthworms decreased significantly following the ingestion of chromium-polluted soil, and their composition differences were significantly correlated with soil acidity and alkalinity. Bacillales, Chryseobacterium, and Citrobacter may have strong abilities to resist chromium and enhance chromium activity in acidic and alkaline soils. There was also a significant correlation between changes in enzyme activity in earthworms and their gut bacterial communities. The bacterial communities, including Pseudomonas and Verminephrobacter, were closely related to the bioavailability of chromium in soil and the degree of chromium stress in earthworms. This study provides insights into the differences in bioremediation for chromium-contaminated soils with different properties and its biological responses.
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BACKGROUND: Conservative treatments have been reported to diminish or resolve clinical symptoms of lumbar intervertebral disc herniation (LIDH) within a few weeks. CASE SUMMARY: Computed tomography and magnetic resonance imaging (MRI) of the lumbar region of a 25-year-old male diagnosed with LIDH showed prolapse of the L5/S2 disc. The disc extended 1.0 cm beyond the vertebral edge and hung along the posterior vertebral edge. The patient elected a conservative treatment regimen that included traditional Chinese medicine (TCM), acupuncture, and massage. During a follow-up period of more than 12 mo, good improvement in pain was reported without complications. MRI of the lumbar region after 12 mo showed obvious reabsorption of the herniation. CONCLUSION: A conservative treatment regimen of TCM, acupuncture, and massage promoted reabsorption of a prolapsed disc.
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Pressure-induced topochemical polymerization of molecular crystals with various stackings is a promising way to synthesize materials with different co-existing sub-structures. Here, by compressing the azobenzene crystal containing two kinds of intermolecular stacking, we synthesized an ordered van der Waals carbon nanoribbon (CNR) heterostructure in one step. Azobenzene polymerizes via a [4 + 2] hetero-Diels-Alder (HDA) reaction of phenylazo-phenyl in layer A and a para-polymerization reaction of phenyl in layer B at 18 GPa, as evidenced by in situ Raman and IR spectroscopies, X-ray diffraction, as well as gas chromatography-mass spectrometry and the solid-state nuclear magnetic resonance of the recovered products. The theoretical calculation shows that the obtained CNR heterostructure has a type II (staggered) band gap alignment. Our work highlights a high-pressure strategy to synthesize bulk CNR heterostructures.
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[This retracts the article DOI: 10.1016/j.omtn.2018.06.011.].
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[This corrects the article DOI: 10.3389/fnmol.2022.852243.].