•DBP would accumulate in vegetable plant Brassica napus.•DBP had a significant effect on properties of soil and vegetables.•Bacteria community of soil-vegetable ecosystem would be changed ...significantly under DBP stress.
Phthalate esters (PAEs) are a type of plasticizer that has aroused great concern due to their mutagenic, teratogenic, and carcinogenic effects, wherefore dibutyl phthalate (DBP) and other PAEs have been listed as priority pollutants. In this study, the impacts of DBP on a soil-vegetable ecosystem were investigated. The results showed that DBP could accumulate within vegetable tissues, and the accumulative effect was enhanced with higher levels of DBP contamination in soils. DBP accumulation also decreased vegetable quality in various ways, including decreased soluble protein content and increased nitrate content. The diversity of bacteria in soils gradually decreased with increasing DBP concentration, while no clear association with endophytic bacteria was observed. Also, the relative abundance, structure, and composition of soil bacterial communities underwent successional change during the DBP degradation period. The variation of bulk soil bacterial community was significantly associated with DBP concentration, while changes in the rhizosphere soil bacteria community were significantly associated with the properties of both soil and vegetables. The results indicated that DBP pollution could increase the health risk from vegetables and alter the biodiversity of indigenous bacteria in soil-vegetable ecosystems, which might further alter ecosystem functions in agricultural fields.
Background and Aims
Cancer cell survival depends on the balance between reactive oxygen species production and scavenging, which is regulated primarily by NRF2 during tumorigenesis. Here, we ...demonstrate that deletion of RBP5‐mediating protein (RMP) in an autonomous mouse model of intrahepatic cholangiocarcinoma (ICC) delays tumor progression.
Approach and Results
RMP‐overexpressing tumor cells exhibited enhanced tolerance to oxidative stress and apoptosis. Mechanistically, RMP competes with NRF2 for binding to the Kelch domain of KEAP1 (Kelch‐like ECH‐associated protein 1) through the E**E motif, leading to decreased NRF2 degradation via ubiquitination, thus increasing NRF2 nuclear translocation and downstream transactivation of antioxidant genes. This RMP‐KEAP1‐NRF2 axis promotes ICC tumorigenesis, metastasis, and drug resistance. Consistent with these findings, the RMP level in human ICC is positively correlated with the protein level of NRF2 and is associated with poor prognosis.
Conclusion
These findings reveal that RMP is involved in the oxidative stress defense program and could be exploited for targeted cancer therapies.
BACKGROUND:Although the mechanisms and pathways mediating ARDS have been studied extensively, less attention has been given to the mechanisms and pathways that counteract injury responses. This study ...found that the apelin-APJ pathway is an endogenous counterinjury mechanism that protects against ARDS. METHODS:Using a rat model of oleic acid (OA)-induced ARDS, the effects of ARDS on apelin and APJ receptor expressions and on APJ receptor binding capacity were examined. The protective effect of activating the apelin-APJ pathway against OA- or lipopolysaccharide (LPS)-induced ARDS was evaluated. RESULTS:ARDS was coupled to upregulations of the apelin and APJ receptor. Rats with OA-induced ARDS had higher lung tissue levels of apelin proprotein and APJ receptor expressions; elevated plasma, BAL fluid (BALF), and lung tissue levels of apelin-36 and apelin-12/13; and an increased apelin-APJ receptor binding capacity. Upregulation of the apelin-APJ system has important pathophysiologic function. Stimulation of the apelin-APJ signaling using receptor agonist apelin-13 alleviated, whereas inhibition of the apelin-APJ signaling using receptor antagonist Ala-apelin-13 exacerbated, OA-induced lung pathologies, extravascular lung water accumulation, capillary-alveolar leakage, and hypoxemia. The APJ receptor agonist inhibited, and the APJ receptor antagonist augmented, OA-induced lung tissue and BALF levels of tumor necrosis factor-α and monocyte chemoattractant protein-1, and plasma and lung tissue levels of malondialdehyde. Postinjury treatment with apelin-13 alleviated lung inflammation and injury and improved oxygenation in OA- and LPS-induced lung injury. CONCLUSIONS:The apelin-APJ signaling pathway is an endogenous anti-injury and organ-protective mechanism that is activated during ARDS to counteract the injury response and to prevent uncontrolled lung injury.
Parkinson's disease (PD) is a neurodegenerative disorder with no absolute cure. The evidence of the involvement of gut microbiota in PD pathogenesis suggests the need to identify certain molecule(s) ...derived from the gut microbiota, which has the potential to manage PD. Osteocalcin (OCN), an osteoblast-secreted protein, has been shown to modulate brain function. Thus, it is of interest to investigate whether OCN could exert protective effect on PD and, if yes, whether the underlying mechanism lies in the subsequent changes in gut microbiota.
The intraperitoneal injection of OCN can effectively ameliorate the motor deficits and dopaminergic neuronal loss in a 6-hydroxydopamine-induced PD mouse model. The further antibiotics treatment and fecal microbiota transplantation experiments confirmed that the gut microbiota was required for OCN-induced protection in PD mice. OCN elevated Bacteroidetes and depleted Firmicutes phyla in the gut microbiota of PD mice with elevated potential of microbial propionate production and was confirmed by fecal propionate levels. Two months of orally administered propionate successfully rescued motor deficits and dopaminergic neuronal loss in PD mice. Furthermore, AR420626, the agonist of FFAR3, which is the receptor of propionate, mimicked the neuroprotective effects of propionate and the ablation of enteric neurons blocked the prevention of dopaminergic neuronal loss by propionate in PD mice.
Together, our results demonstrate that OCN ameliorates motor deficits and dopaminergic neuronal loss in PD mice, modulating gut microbiome and increasing propionate level might be an underlying mechanism responsible for the neuroprotective effects of OCN on PD, and the FFAR3, expressed in enteric nervous system, might be the main action site of propionate. Video abstract.
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•Preparation methods of graphene-like materials from biomass were summarized.•The mechanisms and product characteristics of different methods were discussed.•Common characterization ...instruments to determine the structure were discussed.•Tailored designs of graphene-like material need further investigation.
Two-dimensional graphene materials attracted much attention worldwide because of their superior performance in electronic devices, sensors, and energy storage. However, its application is limited by high cost and insufficient production. The work to find out a simple and environmentally friendly process is highly needed. Designed pyrolysis of biomass precursors can derive graphene-like materials. This review summarizes some typical preparation processes for graphene-like materials synthesis from biomass carbonization via pyrolysis, including salt-based activation, chemical blowing, template-based confinement, coupling with hydrothermal carbonization pretreatment, post exfoliation, and some other methods. The operation of these methods and the performance of obtained graphene-like materials were closely highlighted. The scalability of the techniques and the applications of the biomass graphene-like carbon were also discussed. Some advanced characterization methods, such as SEM, TEM, AFM, Raman, and XPS to determine the graphene-like structure and graphitization degree were also discussed. In the end, some current challenges and future perspectives of the synthesis of these graphene-like materials were concluded.
Our previous studies showed that ferroptosis plays an important role in the acute and subacute stages of spinal cord injury. High intracellular iron levels and low glutathione levels make ...oligodendrocytes vulnerable to cell death after central nervous system trauma. In this study, we established an oligodendrocyte (OLN-93 cell line) model of ferroptosis induced by RSL-3, an inhibitor of glutathione peroxidase 4 (GPX4). RSL-3 significantly increased intracellular concentrations of reactive oxygen species and malondialdehyde. RSL-3 also inhibited the main anti-ferroptosis pathway, i.e., SLC7A11/glutathione/glutathione peroxidase 4 (xCT/GSH/GPX4), and downregulated acyl-coenzyme A synthetase long chain family member 4. Furthermore, we evaluated the ability of several compounds to rescue oligodendrocytes from ferroptosis. Liproxstatin-1 was more potent than edaravone or deferoxamine. Liproxstatin-1 not only inhibited mitochondrial lipid peroxidation, but also restored the expression of GSH, GPX4 and ferroptosis suppressor protein 1. These findings suggest that GPX4 inhibition induces ferroptosis in oligodendrocytes, and that liproxstatin-1 is a potent inhibitor of ferroptosis. Therefore, liproxstatin-1 may be a promising drug for the treatment of central nervous system diseases.
Background
H3 K27M-mutant diffuse midline glioma is a fatal malignancy with no proven medical therapies. The entity predominantly occurs in children and young adults. ONC201 is a small molecule ...selective antagonist of dopamine receptor D2/3 (DRD2/3) with an exceptional safety profile. Following up on a durable response in the first H3 K27M-mutant diffuse midline glioma patient who received ONC201 (NCT02525692), an expanded access program was initiated.
Methods
Patients with H3 K27M-mutant gliomas who received at least prior radiation were eligible. Patients with leptomeningeal spread were excluded. All patients received open-label ONC201 orally once every week. Safety, radiographic assessments, and overall survival were regularly assessed at least every 8 weeks by investigators. As of August 2018, a total of 18 patients with H3 K27M-mutant diffuse midline glioma or DIPG were enrolled to single patient expanded access ONC201 protocols. Among the 18 patients: seven adult (> 20 years old) and seven pediatric (< 20 years old) patients initiated ONC201 with recurrent disease and four pediatric patients initiated ONC201 following radiation, but prior to disease recurrence.
Findings
Among the 14 patients with recurrent disease prior to initiation of ONC201, median progression-free survival is 14 weeks and median overall survival is 17 weeks. Three adults among the 14 recurrent patients remain on treatment progression-free with a median follow up of 49.6 (range 41–76.1) weeks. Among the 4 pediatric patients who initiated adjuvant ONC201 following radiation, two DIPG patients remain progression-free for at least 53 and 81 weeks. Radiographic regressions, including a complete response, were reported by investigators in a subset of patients with thalamic and pontine gliomas, along with improvements in disease-associated neurological symptoms.
Interpretation
The clinical outcomes and radiographic responses in these patients provide the preliminary, and initial clinical proof-of-concept for targeting H3 K27M-mutant diffuse midline glioma with ONC201, regardless of age or location, providing rationale for robust clinical testing of the agent.
5-Hydroxymethylfurfural (HMF) is a platform chemical derived from C6 sugars, which can be transformed into various important chemicals and fuels because of the presence of C&z.dbd;O, C-O and furan ...ring functional groups. In this review, the selective tailoring of these groups in HMF to form 2,5-dimethylfuran, 2,5-dihydromethylfuran, 2,5-dihydromethyltetrahydrofuran, 5-ethoxymethylfurfural, 1,6-hexanediol, long-chain alkanes, 3-(hydroxy-methyl)cyclopentanone,
p
-xylene, 2,5-diformylfuran, 2,5-furandicarboxylic acid and maleic anhydride will be described to gain more insight into the transformation of HMF under various conditions. The focus of this review is on the mechanisms of the catalytic processes and potential design strategies for future catalysts. The activation of the functional groups and the key challenges involved in the precise design of bifunctional catalysts are highlighted. Some examples of "one-pot" transformations of fructose into various chemicals using the HMF platform are also presented.
The catalytic mechanisms and catalyst design strategies for 5-hydroxymethylfural conversion are summarized.
Study Objective
The objective of the present study was to examine the frequency distribution of five single‐nucleotide polymorphisms (SNPs; rs1801394 A>G, rs1532268 C>T, rs162036 A>G, rs10380 C>T, ...and rs9332 C>T) of the methionine synthase reductase (MTRR) gene, their effects on methotrexate (MTX) concentration, and the risk of relapse in a Chinese pediatric population with acute lymphoblastic leukemia (ALL).
Design
This was a retrospective single‐center study, and all analyses were exploratory.
Setting
Pediatric Department of Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Patients
One hundred and forty pediatric patients with ALL.
Intervention
All patients were treated according to the Chinese Children's Leukemia Group (CCLG)‐ALL 2008 protocol.
Measurements and Main Results
Serum MTX concentrations were measured using fluorescence polarization immunoassay. Genotyping of five SNPs was performed using the Sequenom MassARRAY iPLEX platform. Chinese children with ALL had a significantly lower frequency of rs1801394 G than European (EUR) and South Asian (SAS) populations; significantly lower frequency of rs1532268 T than American (AMR), EUR, and SAS populations; and significantly lower frequencies of rs162036 G, rs10380 T, and rs9332 T than African and AMR populations (p < 0.01). Seven haplotypes were observed, with the ACACC being the most common haplotype (49.9%) in our study. The median dose‐normalized concentrations of MTX in serum at 24 h in children with rs1532268 CT and TT genotypes were significantly higher than those with CC genotype (p = 0.04). Compared with children with AA‐CC‐AA‐CC‐CC diplotype, a significantly higher risk of relapse was observed in children with AG‐CC‐AA‐CC‐CC and AG‐CC‐AG‐CC‐CC diplotypes (p = 0.03 and 0.003, respectively).
Conclusions
The present study confirmed the ethnic differences in the distribution of MTRR rs1801394, rs1532268, rs162036, rs10380, and rs9332 polymorphisms. The rs1532268 polymorphism had greater effects on MTX disposition. The AG‐CC‐AA‐CC‐CC and AG‐CC‐AG‐CC‐CC diplotypes were significantly associated with higher risk of relapse of ALL.
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