Difference in the Effect of Applying Bacillus to Control Tomato Verticillium Wilt in Black and Red Soil.

In practical applications, the effectiveness of biological control agents such as Bacillus is often unstable due to different soil environments. Herein, we aimed to explore the control effect and intrinsic mechanism of Bacillus in black soil and red soil in combination with tomato Verticillium wilt. Bacillus application effectively controlled the occurrence of Verticillium wilt in red soil, reducing the incidence by 19.83%, but played a limited role in black soil. Bacillus colonized red soil more efficiently. The Verticillium pathogen decreased by 71.13% and 76.09% after the application of Bacillus combinations in the rhizosphere and bulk of the red soil, respectively, while there was no significant difference in the black soil. Additionally, Bacillus application to red soil significantly promoted phosphorus absorption. Furthermore, it significantly altered the bacterial community in red soil and enriched genes related to pathogen antagonism and phosphorus activation, which jointly participated in soil nutrient activation and disease prevention, promoting tomato plant growth in red soil. This study revealed that the shaping of the bacterial community by native soil may be the key factor affecting the colonization and function of exogenous Bacillus.

The LPS-inactivating enzyme acyloxyacyl hydrolase protects the brain from experimental stroke.

Blood-brain-barrier (BBB) disruption is a pathological hallmark of ischemic stroke, and inflammation occurring at the BBB contributes to the pathogenesis of ischemic brain injury. Lipopolysaccharide (LPS), a cell wall component of Gram-negative bacteria, is elevated in patients with acute stroke. The activity of LPS is controlled by acyloxyacyl hydrolase (AOAH), a host enzyme that deacylates LPS to inactivated forms. However, whether AOAH influences the pathogenesis of ischemic stroke remain elusive. We performed in vivo experiments to explore the role and mechanism of AOAH on neutrophil extravasation, BBB disruption, and brain infarction. We found that AOAH was upregulated in neutrophils in peri-infarct areas from mice with transient focal cerebral ischemia. AOAH deficiency increased neutrophil extravasation into the brain parenchyma and proinflammatory cytokine production, broke down the BBB and worsened stroke outcomes in mice. These effects require Toll-like receptor 4 (TLR4) because absence of TLR4 or pharmacologic inhibition of TLR4 signaling prevented the exacerbated inflammation and BBB damage in Aoah-/- mice after ischemic stroke. Importantly, neutrophil depletion or inhibition of neutrophil trafficking by blocking LFA-1 integrin dramatically reduced stroke-induced BBB breakdown in Aoah-/- mice. Furthermore, virus-mediated overexpression of AOAH induced a substantial decrease in neutrophil recruitment that was accompanied by reducing BBB damage and stroke volumes. Our findings show the importance of AOAH in regulating neutrophil-dependent BBB breakdown and cerebral infarction. Consequently, strategies that modulate AOAH may be a new therapeutic approach for treatment of ischemic stroke.

Microbial regulation of plant secondary metabolites: Impact, mechanisms and prospects.

Plant secondary metabolites possess a wide range of pharmacological activities and play crucial biological roles. They serve as both a defense response during pathogen attack and a valuable drug resource. The role of microorganisms in the regulation of plant secondary metabolism has been widely recognized. The addition of specific microorganisms can increase the synthesis of secondary metabolites, and their beneficial effects depend on environmental factors and plant-related microorganisms. This article summarizes the impact and regulatory mechanisms of different microorganisms on the main secondary metabolic products of plants. We emphasize the mechanisms by which microorganisms regulate hormone levels, nutrient absorption, the supply of precursor substances, and enzyme and gene expression to promote the accumulation of plant secondary metabolites. In addition, the possible negative feedback regulation of microorganisms is discussed. The identification of additional unknown microbes and other driving factors affecting plant secondary metabolism is essential. The prospects for further analysis of medicinal plant genomes and the establishment of a genetic operation system for plant secondary metabolism research are proposed. This study provides new ideas for the use of microbial resources for biological synthesis research and the improvement of crop anti-inverse traits for the use of microbial resources.

Inhibition of Anaplastic Lymphoma Kinase Protects From Ischemic Stroke.

BACKGROUND: Ischemic stroke is often accompanied by oxidative stress and inflammatory response, both of which work synergistically to exacerbate the disruption of the blood-brain barrier and ischemic brain injury. ALK (anaplastic lymphoma kinase), a cancer-associated receptor tyrosine kinase, was found to play a role in oxidative stress and inflammation. In this study, we investigated the role of ALK inhibition in a murine model of ischemic stroke. METHODS: Focal cerebral ischemia was induced by temporary occlusion of the right middle cerebral artery in mice with a filament. The ALK inhibitor alectinib was administered following the stroke. ALOX15 (arachidonic acid 15-lipoxygenase) was overexpressed by adenovirus injection. The immunohistochemistry, Western blot, oxidative stress, inflammation, blood-brain barrier leakage, infarct volume, and functional outcomes were determined. RESULTS: We found that the expression of ALK was markedly increased in the neurovascular unit after cerebral ischemia. Treatment with the ALK inhibitor alectinib reduced the accumulation of reactive oxygen species, lipid peroxidation, and oxidative DNA, increased the vascular levels of antioxidant enzymes, inactivated the vascular NLRP3 (nucleotide-binding oligomerization domain-like receptor protein 3) inflammasome pathway, and reduced vascular inflammation (ICAM-1 [intercellular adhesion molecule-1] and MCP-1 [monocyte chemoattractant protein-1]) after ischemia. Moreover, alectinib reduced the loss of cerebrovascular integrity and blood-brain barrier damage, consequently decreasing brain infarction and neurological deficits. Furthermore, alectinib reduced stroke-evoked ALOX15 expression, whereas virus-mediated overexpression of ALOX15 abolished alectinib-dependent inhibition of oxidative stress and vascular inflammation, blood-brain barrier protection, and neuroprotection, suggesting the protective effects of alectinib for stroke may involve ALOX15. CONCLUSIONS: Our findings demonstrated that alectinib protects from stroke by regulating ischemic signaling cascades and suggest that ALK may be a novel therapeutic target for ischemic stroke.

MgO-modified biochar by modifying hydroxyl and amino groups for selective phosphate removal: Insight into phosphate selectivity adsorption mechanism through experimental and theoretical.

Metal oxides-modified biochars have been widely studied as promising adsorbents for removing phosphate from wastewater discharge. Yet, the low adsorption selectivity towards phosphate severely limits its potential in practical applications. In this study, MgO-modified biochar modified by hydroxyl and amino groups (OH/NH2@MBC) is developed for selective phosphorus recovery from wastewater. As major results, the OH/NH2@MBC exhibits favorable phosphate adsorption performance is superior to that of MBC resin in the presence of co-existing anions (NO3-, Cl-, HCO3- and SO42-) and natural organic matter (humic acid) even actual wastewater, suggesting its superior selectivity towards phosphate. The OH/NH2@MBC shows an excellent phosphate adsorption capacity (43.27 mg/g) and desorption ratio (82.34 %) after five cycles under the condition of anion coexistence (100 mg/L). The experimental and DFT theoretical study reveals that attaching hydroxyl and amino groups onto the MBC surface, which facilitates to inhibiting the side effects of anions (NO3-, Cl-, HCO3-, and SO42-) through Lewis acid-base sites, hydrogen bonds, and metal affinity, and preferentially select adsorption P, contributing greatly to improve phosphate adsorption selectivity. Importantly, the presence of amino and hydroxyl groups can reduce the Fermi level of OH/NH2@MgO(220) and OH/NH2@MgO(200) and improve the adsorption selection for HPO42-. This study provides an effective strategy for enhancing the adsorption selectivity of metal oxides-modified biochars towards phosphate through modifying functional groups.

Neddylation in the chronically hypoperfused corpus callosum: MLN4924 reduces blood-brain barrier injury via ERK5/KLF2 signaling.

Blood-brain barrier (BBB) breakdown and cerebrovascular dysfunction may contribute to the pathology in white matter lesions and consequent cognitive decline caused by cerebral hypoperfusion. Neddylation is the process of attaching a ubiquitin-like molecule NEDD8 (neuronal precursor cell-expressed developmentally downregulated protein 8) to specific targets. By modifying protein substrates, neddylation plays critical roles in various important biological processes. However, whether neddylation influences the pathogenesis of hypoperfused brain remains unclear. In the present study, cerebral hypoperfusion-induced white matter lesions were produced by bilateral common carotid artery stenosis in mice. The function of the neddylation pathway, BBB integrity, cerebrovascular dysfunction, myelin density in the corpus callosum and cognitive function were determined. We show that NEDD8 conjugation aberrantly amplified in microvascular endothelium in the corpus callosum following cerebral hypoperfusion. MLN4924, a small-molecule inhibitor of NEDD8-activating enzyme currently in clinical trials, preserved BBB integrity, attenuated glial activation and enhanced oligodendrocyte differentiation, and reduced hypoperfusion-induced white matter lesions in the corpus callosum and thus improved cognitive performance via inactivating cullin-RING E3 ligase (CRL). Administration of MLN4924 caused the accumulation of ERK5 and KLF2. The ERK5 inhibitor BIX 02189, down-regulated MLN4924-induced activation of KLF2 and reversed MLN4924-mediated increase in pericyte coverage and junctional proteins. Furthermore, BIX 02189 blocked MLN4924-afforded protection against BBB disruption and white matter lesions in the corpus callosum. Collectively, our results revealed that neddylation impairs vascular function and thus exacerbated the pathology of hypoperfused brain and that inhibition of neddylation with MLN4924 may offer novel therapeutic opportunities for cerebral hypoperfusion-associated cognitive impairment.

Phosphate-solubilizing microorganisms regulate the release and transformation of phosphorus in biochar-based slow-release fertilizer.

Coupling phosphate-solubilizing microorganisms (PSM) can improve the availability of phosphorous (P) in biochar-based slow-release P fertilizers (BPF). However, the mechanism in release and transformation of P in BPF regulated by PSM is still unclear. Herein, the biocompatibility and the adhesion behaviors of BPF and PSM (Enterobacter hormaechei Rs-198) in soil were firstly studied, and a 90 days' laboratory-scale soil incubation experiment of BPF and Rs-198 was performed to study the transformation of P of BPF. The results show that BPF has a good biocompatibility for Rs-198 due to its low aromaticity, graphitization and free radicals' content (0.084 mg/g). Rs-198 are adhered to the surface of BPF in soil due to the high negative secondary energy minimum and low total interaction energy between Rs-198 and BPF. Available P in the incubation of BPF and Rs-198 (BR treatment) is significantly higher than that of the incubation of BPF (BF treatment) at initial 60 days. However, the content of available P in BR treatment is much lower compared with that in BF treatment on day 90, which is attributed to the entrapment of released P from BPF by Rs-198 and the formation of polyphosphate (polyP) rather than bound with soil mineral. Overall, this study presents new insights into the transformation of P in BPF regulated by PSM.

The NEDD8-activating enzyme inhibitor MLN4924 reduces ischemic brain injury in mice.

Blood-brain barrier (BBB) breakdown and inflammation occurring at the BBB have a key, mainly a deleterious role in the pathophysiology of ischemic stroke. Neddylation is a ubiquitylation-like pathway that is critical in various cellular functions by conjugating neuronal precursor cell-expressed developmentally down-regulated protein 8 (NEDD8) to target proteins. However, the roles of neddylation pathway in ischemic stroke remain elusive. Here, we report that NEDD8 conjugation increased during acute phase after ischemic stroke and was present in intravascular and intraparenchymal neutrophils. Inhibition of neddylation by MLN4924, also known as pevonedistat, inactivated cullin-RING E3 ligase (CRL), and reduced brain infarction and improved functional outcomes. MLN4924 treatment induced the accumulation of the CRL substrate neurofibromatosis 1 (NF1). By using virus-mediated NF1 silencing, we show that NF1 knockdown abolished MLN4924-dependent inhibition of neutrophil trafficking. These effects were mediated through activation of endothelial P-selectin and intercellular adhesion molecule-1 (ICAM-1), and blocking antibodies against P-selectin or anti-ICAM-1 antibodies reversed NF1 silencing-induced increase in neutrophil infiltration in MLN4924-treated mice. Furthermore, we found that NF1 silencing blocked MLN4924-afforded BBB protection and neuroprotection through activation of protein kinase C δ (PKCδ), myristoylated alanine-rich C-kinase substrate (MARCKS), and myosin light chain (MLC) in cerebral microvessels after ischemic stroke, and treatment of mice with the PKCδ inhibitor rottlerin reduced this increased BBB permeability. Our study demonstrated that increased neddylation promoted neutrophil trafficking and thus exacerbated injury of the BBB and stroke outcomes. We suggest that the neddylation inhibition may be beneficial in ischemic stroke.

Neutrophil extracellular traps promote tPA-induced brain hemorrhage via cGAS in mice with stroke.

Intracerebral hemorrhage associated with thrombolytic therapy with tissue plasminogen activator (tPA) in acute ischemic stroke continues to present a major clinical problem. Here, we report that infusion of tPA resulted in a significant increase in markers of neutrophil extracellular traps (NETs) in the ischemic cortex and plasma of mice subjected to photothrombotic middle cerebral artery occlusion. Peptidylarginine deiminase 4 (PAD4), a critical enzyme for NET formation, is also significantly upregulated in the ischemic brains of tPA-treated mice. Blood-brain barrier (BBB) disruption after ischemic challenge in an in vitro model of BBB was exacerbated after exposure to NETs. Importantly, disruption of NETs by DNase I or inhibition of NET production by PAD4 deficiency restored tPA-induced loss of BBB integrity and consequently decreased tPA-associated brain hemorrhage after ischemic stroke. Furthermore, either DNase I or PAD4 deficiency reversed tPA-mediated upregulation of the DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS). Administration of cGAMP after stroke abolished DNase I-mediated downregulation of the STING pathway and type 1 interferon production and blocked the antihemorrhagic effect of DNase I in tPA-treated mice. We also show that tPA-associated brain hemorrhage after ischemic stroke was significantly reduced in cGas-/- mice. Collectively, these findings demonstrate that NETs significantly contribute to tPA-induced BBB breakdown in the ischemic brain and suggest that targeting NETs or cGAS may ameliorate thrombolytic therapy for ischemic stroke by reducing tPA-associated hemorrhage.

Synthesis and characterisation of seleno-Cynomorium songaricum Rupr. polysaccharide.

In this article, the structural properties of Cynomorium songaricum Rupr. polysaccharide (CSP) after selenylation were investigated. The crude polysaccharide was obtained from C. songaricum Rupr. by water extraction followed by ethanol precipitation and freeze vacuum drying. Then selenylation of CSP has been accomplished by employing sodium selenite to modify the polysaccharide under the catalysis of nitric acid-barium chloride. After selenylation, the sugar content and the molecular weight increased but the protein content reduced. The maximum selenic content determined by ICP-AES was 2925 microg g(-1). The selenide CSP (Se-CSP) was characterised by the methods of UV spectra, FT-IR, Raman spectra and X-ray photoelectron spectroscopy. The results showed that the hydroxyl hydrogen of the sugar moieties was substituted by Se=O. Thermal stability of Se-CSP was also measured by TG-DTA.