Lignin is a carbon-rich renewable source owning aromatic structure units, which is an important constituent in biomass. Hydrothermal conversion of lignin is widely studied as a promising method to ...produce not only bioenergy but also value-added useful chemicals. Fuel gas, aromatic aldehydes and phenolic products can be obtained from lignin hydrothermal gasification, wet oxidation and hydrothermal liquefaction, respectively. This article discusses and compares the three methods of lignin hydrothermal conversion, including their process parameters, possible conversion routes, catalysts, application of products. Effects of hot-compressed organic solvent–water mixture solution on conversion of lignin and effects of lignin in biomass hydrothermal conversion are commented. Wet oxidation of lignin is an efficient mean of recovering value-added aromatic aldehydes, especially vanillin. Hydrothermal liquefaction of lignin is a promising way of recovering phenolics-rich bio-oils. Both aromatic aldehyde and phenolic compound are important chemical intermediates. There are strict requirements of process conditions and relative high costs to get fuel gas from direct hydrothermal gasification of lignin. However, further studies on improving gasification of lignin seem necessary in order to get fuel gas from hydrothermal gasification of the whole biomass.
Major depressive disorder (MDD) is a highly prevalent psychiatric disorder, and inflammation has been considered crucial components of the pathogenesis of depression. NLRP1 inflammasome-driven ...inflammatory response is believed to participate in many neurological disorders. However, it is unclear whether NLRP1 inflammasome is implicated in the development of depression.
Animal models of depression were established by four different chronic stress stimuli including chronic unpredictable mild stress (CUMS), chronic restrain stress (CRS), chronic social defeat stress (CSDS), and repeat social defeat stress (RSDS). Depressive-like behaviors were determined by sucrose preference test (SPT), forced swim test (FST), tail-suspension test (TST), open-field test (OFT), social interaction test (SIT), and light-dark test (LDT). The expression of NLRP1 inflammasome complexes, BDNF, and CXCL1/CXCR2 were tested by western blot and quantitative real-time PCR. The levels of inflammatory cytokines were tested by enzyme-linked immunosorbent assay (ELISA) kits. Nlrp1a knockdown was performed by an adeno-associated virus (AAV) vector containing Nlrp1a-shRNA-eGFP infusion.
Chronic stress stimuli activated hippocampal NLRP1 inflammasome and promoted the release of pro-inflammatory cytokines IL-1β, IL-18, IL-6, and TNF-α in mice. Hippocampal Nlrp1a knockdown prevented NLRP1 inflammasome-driven inflammatory response and ameliorated stress-induced depressive-like behaviors. Also, chronic stress stimuli caused the increase in hippocampal CXCL1/CXCR2 expression and low BDNF levels in mice. Interestingly, Nlrp1a knockdown inhibited the up-regulation of CXCL1/CXCR2 expression and restored BDNF levels in the hippocampus.
NLRP1 inflammasome-driven inflammatory response contributes to chronic stress induced depressive-like behaviors and the mechanism may be related to CXCL1/CXCR2/BDNF signaling pathway. Thus, NLRP1 inflammasome could become a potential antidepressant target.
Abstract
Background
The immune system plays a vital role in the pathological process of ischaemic stroke. However, the exact immune-related mechanism remains unclear. The current research aimed to ...identify immune-related key genes associated with ischaemic stroke.
Methods
CIBERSORT was utilized to reveal the immune cell infiltration pattern in ischaemic stroke patients. Meanwhile, a weighted gene coexpression network analysis (WGCNA) was utilized to identify meaningful modules significantly correlated with ischaemic stroke. The characteristic genes correlated with ischaemic stroke were identified by the following two machine learning methods: the support vector machine-recursive feature elimination (SVM-RFE) algorithm and least absolute shrinkage and selection operator (LASSO) logistic regression.
Results
The CIBERSORT results suggested that there was a decreased infiltration of naive CD4 T cells, CD8 T cells, resting mast cells and eosinophils and an increased infiltration of neutrophils, M0 macrophages and activated memory CD4 T cells in ischaemic stroke patients. Then, three significant modules (pink, brown and cyan) were identified to be significantly associated with ischaemic stroke. The gene enrichment analysis indicated that 519 genes in the above three modules were mainly involved in several inflammatory or immune-related signalling pathways and biological processes. Eight hub genes (
ADM
,
ANXA3
,
CARD6
,
CPQ
,
SLC22A4
,
UBE2S
,
VIM
and
ZFP36
) were revealed to be significantly correlated with ischaemic stroke by the LASSO logistic regression and SVM-RFE algorithm. The external validation combined with a RT‒qPCR analysis revealed that the expression levels of
ADM
,
ANXA3
,
SLC22A4
and
VIM
were significantly increased in ischaemic stroke patients and that these key genes were positively associated with neutrophils and M0 macrophages and negatively correlated with CD8 T cells. The mean AUC value of
ADM
,
ANXA3
,
SLC22A4
and
VIM
was 0.80, 0.87, 0.91 and 0.88 in the training set, 0.85, 0.77, 0.86 and 0.72 in the testing set and 0.87, 0.83, 0.88 and 0.91 in the validation samples, respectively.
Conclusions
These results suggest that the
ADM
,
ANXA3
,
SLC22A4
and
VIM
genes are reliable serum markers for the diagnosis of ischaemic stroke and that immune cell infiltration plays a crucial role in the occurrence and development of ischaemic stroke.
Accurate risk stratification for patients with stage II/III colon cancer is pivotal for postoperative treatment decisions. Here, we aimed to identify and validate a circRNA‐based signature that could ...improve postoperative prognostic stratification for these patients. In current retrospective analysis, we included 667 patients with R0 resected stage II/III colon cancer. Using RNA‐seq analysis of 20 paired frozen tissues collected postoperation, we profiled differential circRNA expression between patients with and without recurrence, followed by quantitative validation. With clinical information, we generated a four‐circRNA‐based cirScore to classify patients into high‐risk and low‐risk groups in the training cohort. The patients with high cirScores in the training cohort had a shorter disease‐free survival (DFS) and overall survival (OS) than patients with low cirScores. The prognostic capacity of the classifier was validated in the internal and external cohorts. Loss‐of‐function assays indicated that the selected circRNAs played functional roles in colon cancer progression. Overall, our four‐circRNA‐based classifier is a reliable prognostic tool for postoperative disease recurrence in patients with stage II/III colon cancer.
Synopsis
Novel molecular biomarkers allowing for better prognostic stratification of patients with stage II/III colon cancer are urgently needed. In this study, a circRNA‐based signature (cirScore) was identified and validated to improve postoperative risk‐stratification for these patients.
Dysregulated circRNAs showed strong classification capacities in distinguishing between recurrent and nonrecurrent colon cancer patients.
The proposed four‐cirRNA‐based cirScore can effectively classify patients with stage II/III colon cancer into groups with low and high risks of disease recurrence.
The loss‐of‐function assay indicated that the representative circRNAs plays functional roles in the sophisticated regulation of colon cancer progression.
Nomograms incorporating the cirScore with existing risk factors achieved excellent accuracy for predicting disease‐free and overall survival for patients with stage II/III colon cancer.
Novel molecular biomarkers allowing for better prognostic stratification of patients with stage II/III colon cancer are urgently needed. In this study, a circRNA‐based signature (cirScore) was identified and validated to improve postoperative risk‐stratification for these patients.
The long noncoding RNA H19 is overexpressed in many cancers and acts as an oncogene. Here, we explored the role of H19 in breast cancer cells, including the effect of H19 on proliferation, migration, ...and invasion of breast cancer cells. We also investigated the relation of H19 to microRNA miR‐93‐5p and signal transducers and activators of transcription 3 (STAT3), the target gene of miR‐93‐5p. Ectopic expression of H19 in MCF‐7 cells and knockdown of H19 in MDA‐MB‐231 cells showed that overexpression of H19 promoted proliferation, migration, and invasion, whereas knockdown of H19 reduced proliferation, migration, and invasion in vitro. Dual‐luciferase reporter assays and RNA‐binding protein immunoprecipitation assays proved that H19 was a target of miR‐93‐5p. In addition, H19 antagonized the downregulation of miR‐93‐5p on its target STAT3 and antagonized miR‐93‐5p‐mediated cell proliferation. Our study revealed a new network in the expression of STAT3 involving H19 and miR‐93‐5p, which may contribute to a better understanding of breast cancer pathogenesis and provide new insights into the treatment of this disease.
H19 antagonized the downregulation of miR‐93‐5p on its target signal transducers and activators of transcription 3 (STAT3) and inhibited miR‐93‐5p‐induced cell proliferation. Our study revealed a new network in the expression of STAT3 involving H19 and miR‐93‐5p, which may contribute to a better understanding of breast cancer pathogenesis and provide new insights into the treatment of this disease.
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► Lignin was used for selective production of 4-ethylphenolics via mild hydrogenolysis. ► 3.1% 4-Ethylphenol and 1.3% 4-ethylguaiacol based on lignin were obtained simultaneously. ► ...This new technique would be a promising method for the substitution of petrochemical route.
Selective production of 4-ethylphenolics from lignin via mild hydrogenolysis was reported in this short communication. The hydrogenolysis of lignin was carried out in an autoclave with 65 vol.% ethanol/water as solvent, with 5% Ru/C, Pd/C and Pt/C as catalysts. The influences of catalysts, lignin species, and reaction conditions including reaction temperature, reaction time, and initial H2 pressure on yield of target compounds were investigated. 3.1% 4-Ethylphenol and 1.3% 4-ethylguaiacol based on lignin could be obtained simultaneously from hydrogenolysis of corn stalk lignin, which is approximate to the yield obtained from petrochemical route. The results of this work showed that this novel method is a quite promising technique for the substitution of petrochemical route.
Assembly of microtubule-associated protein tau into filamentous inclusions underlies a range of neurodegenerative diseases. Tau filaments adopt different conformations in Alzheimer's and Pick's ...diseases. Here, we used cryo- and immuno- electron microscopy to characterise filaments that were assembled from recombinant full-length human tau with four (2N4R) or three (2N3R) microtubule-binding repeats in the presence of heparin. 2N4R tau assembles into multiple types of filaments, and the structures of three types reveal similar 'kinked hairpin' folds, in which the second and third repeats pack against each other. 2N3R tau filaments are structurally homogeneous, and adopt a dimeric core, where the third repeats of two tau molecules pack in a parallel manner. The heparin-induced tau filaments differ from those of Alzheimer's or Pick's disease, which have larger cores with different repeat compositions. Our results illustrate the structural versatility of amyloid filaments, and raise questions about the relevance of in vitro assembly.
Tumor cells metabolize more glucose to lactate in aerobic or hypoxic conditions than normal cells. Pyruvate kinase isoenzyme type M2 (PKM2) is crucial for tumor cell aerobic glycolysis. We ...established a role for let‐7a‐5p/Stat3/hnRNP‐A1/PKM2 signaling in breast cancer cell glucose metabolism. PKM2 depletion via small interfering RNA (siRNA) inhibits cell proliferation and aerobic glycolysis in breast cancer cells. Signal transducer and activator of transcription 3 (Stat3) promotes upregulation of heterogeneous nuclear ribonucleoprotein (hnRNP)‐A1 expression, hnRNP‐A1 binding to pyruvate kinase isoenzyme (PKM) pre messenger RNA, and the subsequent formation of PKM2. This pathway is downregulated by the microRNA let‐7a‐5p, which functionally targets Stat3, whereas hnRNP‐A1 blocks the biogenesis of let‐7a‐5p to counteract its ability to downregulate the Stat3/hnRNP‐A1/PKM2 signaling pathway. The downregulation of Stat3/hnRNP‐A1/PKM2 by let‐7a‐5p is verified using a breast cancer. These results suggest that let‐7a‐5p, Stat3, and hnRNP‐A1 form a feedback loop, thereby regulating PKM2 expression to modulate glucose metabolism of breast cancer cells. These findings elucidate a new pathway mediating aerobic glycolysis in breast cancers and provide an attractive potential target for breast cancer therapeutic intervention.
In this study, we explored the role of let‐7a‐5p and pyruvate kinase isoenzyme type M2 (PKM2) in the aerobic glycolysis of breast cancer cells. We found that let‐7a‐5p, signal transducer and activator of transcription 3 (Stat3), and heterogeneous nuclear ribonucleoprotein (hnRNP)‐A1 can form a feedback loop to regulate PKM2 expression, thereby regulating the glucose metabolism and growth of breast cancer cells. Thus, the let‐7a‐5p/Stat3/hnRNP‐A1/PKM2 signaling pathway may serve as a potential target for breast cancer treatment.
Friend leukemia integration 1 (FLI1) is an ETS transcription factor family member. Here, we identified cg11017065 as the most hyper‐methylated cytosine and guanine (CpG) in colorectal cancer (CRC), ...which belongs to the FLI1 gene. Moreover, integrated bioinformatics prediction and analysis of our cohort showed that FLI1 expression was downregulated and DNA methylation was elevated in CRC. Bioinformatics prediction also indicated that patients overexpressing FLI1 had higher survival rates than those with low FLI1 expression. CRC cells with ectopic expression of FLI1 had reduced invasion, migration, cloning ability and increased apoptosis. Furthermore, DNA‐methyltransferase 3b (DNMT3b) was found to be significantly overexpressed in CRC, and low DNMT3b expression predicted a prolonged survival. DNMT3b bound to the FLI1 promoter. Inhibition of DNMT3b increased FLI1 expression and inhibited the malignant phenotype of CRC cells. Inhibition of FLI1 reversed the phenotypic modulation by DNMT3b depletion in vitro and in vivo. In conclusion, our data indicate that DNMT3b potentiates CRC cell proliferation, migration, and invasion through downregulating FLI1.
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