ExpressVis: a biologist-oriented interactive web server for exploring multi-omics data.

In the era of life-omics, huge amounts of multi-omics data have been generated and widely used in biomedical research. It is challenging for biologists with limited programming skills to obtain biological insights from multi-omics data. Thus, a biologist-oriented platform containing visualization functions is needed to make complex omics data digestible. Here, we propose an easy-to-use, interactive web server named ExpressVis. In ExpressVis, users can prepare datasets; perform differential expression analysis, clustering analysis, and survival analysis; and integrate expression data with protein-protein interaction networks and pathway maps. These analyses are organized into six modules. Users can use each module independently or use several modules interactively. ExpressVis displays analysis results in interactive figures and tables, and provides comprehensive interactive operations in each figure and table, between figures or tables in each module, and among different modules. It is freely accessible at https://omicsmining.ncpsb.org.cn/ExpressVis and does not require login. To test the performance of ExpressVis for multi-omics studies of clinical cohorts, we re-analyzed a published hepatocellular carcinoma dataset and reproduced their main findings, suggesting that ExpressVis is convenient enough to analyze multi-omics data. Based on its complete analysis processes and unique interactive operations, ExpressVis provides an easy-to-use solution for exploring multi-omics data.

ABRO1 promotes NLRP3 inflammasome activation through regulation of NLRP3 deubiquitination.

Deubiquitination of NLRP3 has been suggested to contribute to inflammasome activation, but the roles and molecular mechanisms are still unclear. We here demonstrate that ABRO1, a subunit of the BRISC deubiquitinase complex, is necessary for optimal NLRP3-ASC complex formation, ASC oligomerization, caspase-1 activation, and IL-1ß and IL-18 production upon treatment with NLRP3 ligands after the priming step, indicating that efficient NLRP3 activation requires ABRO1. Moreover, we report that ABRO1 deficiency results in a remarkable attenuation in the syndrome severity of NLRP3-associated inflammatory diseases, including MSU- and Alum-induced peritonitis and LPS-induced sepsis in mice. Mechanistic studies reveal that LPS priming induces ABRO1 binding to NLRP3 in an S194 phosphorylation-dependent manner, subsequently recruiting the BRISC to remove K63-linked ubiquitin chains of NLRP3 upon stimulation with activators. Furthermore, deficiency of BRCC3, the catalytically active component of BRISC, displays similar phenotypes to ABRO1 knockout mice. Our findings reveal an ABRO1-mediated regulatory signaling system that controls activation of the NLRP3 inflammasome and provide novel potential targets for treating NLRP3-associated inflammatory diseases.

VPS37C facilitates erythroid differentiation by promoting EKLF stability.

The process of erythroid differentiation is orchestrated at the molecular level by a complex network of transcription factors. Erythroid Krüppel-like factor (EKLF/KLF1) is a master erythroid gene regulator that directly regulates most aspects of terminal erythroid differentiation. However, the underlying regulatory mechanisms of EKLF protein stability are still largely unknown. In this study, we identified Vacuolar protein sorting 37 C (VPS37C), a core subunit of the Endosomal sorting complex required for transport-I (ESCRT-I) complex, as an essential regulator of EKLF stability. Our study showed that VPS37C interacts with EKLF and prevents K48-linked polyubiquitination of EKLF and proteasome-mediated EKLF degradation, thus enhancing EKLF protein stability and transcriptional activity. VPS37C overexpression in murine erythroleukemia (MEL) cells promotes hexamethylene bisacetamide (HMBA)-induced erythroid differentiation manifested by up-regulating erythroid-specific EKLF target genes and increasing benzidine-positive cells. In contrast, VPS37C knockdown inhibits HMBA-induced MEL cell erythroid differentiation. Particularly, the restoration of EKLF expression in VPS37C-knockdown MEL cells reverses erythroid-specific gene expression and hemoglobin production. Collectively, our study demonstrated VPS37C is a novel regulator of EKLF ubiquitination and degradation, which plays a positive role in erythroid differentiation of MEL cells by enhancing EKLF protein stability.

Notoginsenoside R1 can inhibit the interaction between FGF1 and VEGFA to retard podocyte apoptosis.

BACKGROUND: Diabetic nephropathy (DN) is a chronic condition resulting from microangiopathy in a high-glucose environment. The evaluation of vascular injury in DN has primarily focused on active molecules of VEGF, namely VEGFA and VEGF2(F2R). Notoginsenoside R1 (NGR1), a traditional anti-inflammatory medication, exhibits vascular activity. Therefore, identifying classical drugs with vascular inflammatory protection for the treatment of DN is a valuable pursuit. METHODS: The "Limma" method was employed to analyze the glomerular transcriptome data, while the Spearman algorithm for Swiss target prediction was utilized to analyze the drug targets of NGR1. The molecular docking technique was employed to investigate the relationship between vascular active drug targets, and the COIP experiment was conducted to verify the interaction between fibroblast growth factor 1 (FGF1) and VEGFA in relation to NGR1 and drug targets. RESULTS: According to the Swiss target prediction, the LEU32(b) site of the Vascular Endothelial Growth Factor A (VEGFA) protein, as well as the Lys112(a), SER116(a), and HIS102(b) sites of the Fibroblast Growth Factor 1 (FGF1) protein, are potential binding sites for NGR1 through hydrogen bonding. Additionally, the Co-immunoprecipitation (COIP) results suggest that VEGFA and FGF1 proteins can interact with each other, and NGR1 can impede this interaction. Furthermore, NGR1 can suppress the expression of VEGFA and FGF1 in a high-glucose environment, thereby decelerating podocyte apoptosis. CONCLUSION: The inhibition of the interaction between FGF1 and VEGFA by NGR1 has been observed to decelerate podocyte apoptosis.

Knockdown of Dcr1 and Dcr2 limits the lethal effect of C-factor in Chilo suppressalis.

Dicer is a highly conserved ribonuclease in evolution. It belongs to the RNase III family and can specifically recognize and cleave double-stranded RNA (dsRNA). In this study, the genome and transcriptome of Chilo suppressalis were analyzed, and it was found that there were two members in the Dicer family, named Dcr1 and Dcr2. The dsRNAs of Dcr1 and Dcr2 genes were synthesized and fed to C. suppressalis larvae. The C-factor of C. suppressalis was selected as the marker gene. The results showed that both Dcr1 and Dcr2 genes were significantly knocked down. The larval mortality was significantly reduced by 43.50% (p < 0.05) after feeding on dsC-factor and dsDcr1. The transcription levels of C-factor genes were significantly increased by 33.95% (p < 0.05) and 32.94% (p < 0.05) when the larvae fed with dsDcr2 + dsC-factor for 72 h and 96 h, respectively. Furthermore, the mortality was significantly decreased by 79% (p < 0.05) after feeding dsC-factor and dsDcr2. These findings imply that Dcr1 can decrease the lethal effect of C-factor gene but cannot affect its RNAi efficiency and Dcr2 can decrease the lethal effect of C-factor gene by inhibiting RNAi efficiency.

The intellectual base and global trends in inflammation of diabetic kidney disease: a bibliometric analysis.

Diabetic kidney disease (DKD) is a severe complication of diabetes mellitus (DM). The literature on DKD inflammation research has experienced substantial growth. However, there is a lack of bibliometric analyses. This study aimed to examine the existing research on inflammation in DKD by analyzing articles published in the Web of Science Core Collection (WOSCC) over the past 30 years. We conducted a visualization analysis using several software, including CiteSpace and VOSviewer. We found that the literature on inflammation research in DKD has experienced substantial growth, indicating a rising interest in this developing area of study. In this field, Navarro-Gonzalez, JF is the most frequently cited author, Kidney International is the most frequently cited journal, China had the highest number of publications in the field of DKD inflammation, and Monash University emerged as the institution with the most published research. The research area on inflammation in DKD primarily centers around the investigation of 'Glycation end-products', 'chronic kidney disease', and 'diabetic nephropathy'. The emerging research trends in this field will focus on the 'Gut microbiota', 'NLRP3 inflammasome', 'autophagy', 'pyroptosis', 'sglt2 inhibitor', and 'therapeutic target'. Future research on DKD may focus on further exploring the inflammatory response, identifying specific therapeutic targets, studying biomarkers, investigating stem cell therapy and tissue engineering, and exploring gene therapy and gene editing. In summary, this study examines the main areas of study, frontiers, and trends in DKD inflammation, which have significant implications for future research.

Advances in the Biosynthesis of Terpenoids and Their Ecological Functions in Plant Resistance.

Secondary metabolism plays an important role in the adaptation of plants to their environments, particularly by mediating bio-interactions and protecting plants from herbivores, insects, and pathogens. Terpenoids form the largest group of plant secondary metabolites, and their biosynthesis and regulation are extremely complicated. Terpenoids are key players in the interactions and defense reactions between plants, microorganisms, and animals. Terpene compounds are of great significance both to plants themselves and the ecological environment. On the one hand, while protecting plants themselves, they can also have an impact on the environment, thereby affecting the evolution of plant communities and even ecosystems. On the other hand, their economic value is gradually becoming clear in various aspects of human life; their potential is enormous, and they have broad application prospects. Therefore, research on terpenoids is crucial for plants, especially crops. This review paper is mainly focused on the following six aspects: plant terpenes (especially terpene volatiles and plant defense); their ecological functions; their biosynthesis and transport; related synthesis genes and their regulation; terpene homologues; and research and application prospects. We will provide readers with a systematic introduction to terpenoids covering the above aspects.

Transcriptome Analysis Revealed the Dynamic and Rapid Transcriptional Reprogramming Involved in Cold Stress and Related Core Genes in the Rice Seedling Stage.

Cold damage is one of the most important environmental factors influencing crop growth, development, and production. In this study, we generated a pair of near-isogenic lines (NILs), Towada and ZL31, and Towada showed more cold sensitivity than ZL31 in the rice seedling stage. To explore the transcriptional regulation mechanism and the reason for phenotypic divergence of the two lines in response to cold stress, an in-depth comparative transcriptome study under cold stress was carried out. Our analysis uncovered that rapid and high-amplitude transcriptional reprogramming occurred in the early stage of cold treatment. GO enrichment and KEGG pathway analysis indicated that genes of the response to stress, environmental adaptation, signal transduction, metabolism, photosynthesis, and the MAPK signaling pathway might form the main part of the engine for transcriptional reprogramming in response to cold stress. Furthermore, we identified four core genes, OsWRKY24, OsCAT2, OsJAZ9, and OsRR6, that were potential candidates affecting the cold sensitivity of Towada and ZL31. Genome re-sequencing analysis between the two lines revealed that only OsWRKY24 contained sequence variations which may change its transcript abundance. Our study not only provides novel insights into the cold-related transcriptional reprogramming process, but also highlights the potential candidates involved in cold stress.

Relevance of the pyroptosis-related inflammasome drug targets in the Chuanxiong to improve diabetic nephropathy.

BACKGROUND: A chronic inflammatory disease caused by disturbances in metabolism, diabetic nephropathy (DN) is a chronic inflammatory disease. Pyroptosis is a novel form of programmed cell death in many inflammation-related diseases, including DN. Therefore, pyroptosis could be a promising target for DN therapy. METHODS: To get the components and pharmacodynamic targets of Chuanxiong, we identified by searching TCMID, TCMSP, ETCM and HERB databases. Then, from the Molecular Signatures Database (MSigDB) and Gene Ontology (GO) database, pyroptosis genes were collected. Identification of critical genes in DN by bioinformatics analysis and then using the ConsensusClusterPlus package to divide the express data of diff genes into some subgroups with different levels of pyroptosis; the WGCNA machine algorithm was used to simulate the mechanism Chuanxiong improving DN. RESULTS: In this study, we found DHCR24, ANXA1, HMOX1, CDH13, ALDH1A1, LTF, CHI3L1, CACNB2, and MTHFD2 interacted with the diff genes of DN. We used GSE96804 as a validation set to evaluate the changes of APIP, CASP6, CHMP2B, CYCS, DPP8, and TP53 in four different cell proapoptotic states. WGCNA analysis showed that DHCR24, CHI3L1, and CACNB2 had significant changes in different cell proapoptotic levels. In the experimental stage, we also confirmed that the active ingredients of Chuanxiong could improve the inflammatory state and the levels of pyroptosis under high glucose. CONCLUSION: The improvement of DN by Chuanxiong is related to the change of pyroptosis.

GPS2 promotes erythroid differentiation by control of the stability of EKLF protein.

Erythropoiesis is a complex multistage process that involves differentiation of early erythroid progenitors to enucleated mature red blood cells, in which lineage-specific transcription factors play essential roles. Erythroid Krüppel-like factor (EKLF/KLF1) is a pleiotropic erythroid transcription factor that is required for the proper maturation of the erythroid cells, whose expression and activation are tightly controlled in a temporal and differentiation stage-specific manner. Here, we uncover a novel role of G-protein pathway suppressor 2 (GPS2), a subunit of the nuclear receptor corepressor/silencing mediator of retinoic acid and thyroid hormone receptor corepressor complex, in erythrocyte differentiation. Our study demonstrates that knockdown of GPS2 significantly suppresses erythroid differentiation of human CD34+ cells cultured in vitro and xenotransplanted in nonobese diabetic/severe combined immunodeficiency/interleukin-2 receptor γ-chain null mice. Moreover, global deletion of GPS2 in mice causes impaired erythropoiesis in the fetal liver and leads to severe anemia. Flow cytometric analysis and Wright-Giemsa staining show a defective differentiation at late stages of erythropoiesis in Gps2-/- embryos. Mechanistically, GPS2 interacts with EKLF and prevents proteasome-mediated degradation of EKLF, thereby increasing EKLF stability and transcriptional activity. Moreover, we identify the amino acids 191-230 region in EKLF protein, responsible for GPS2 binding, that is highly conserved in mammals and essential for EKLF protein stability. Collectively, our study uncovers a previously unknown role of GPS2 as a posttranslational regulator that enhances the stability of EKLF protein and thereby promotes erythroid differentiation.

Hybrid Diterpenic Meroterpenoids from an Endophytic Penicillium sp. Induced by Chemical Epigenetic Manipulation.

Cultivation of an endophytic fungus Penicillium sp. KMU18029 with suberanilohydroxamic acid (SAHA), a histone deacetylase inhibitor, led to the isolation of two pairs of diterpenic meroterpenoids with a unique natural product framework combining features of pyripyropenes and decaturins/oxalicines, pyrandecarurins A (1) and B (2), pileotin A (3) and B (4), along with their potential precursor decaturenoid (5). Compounds 1, 2, 4, and 5 were new. The structures of 1-5 were elucidated by extensive spectroscopic analyses. The absolute configurations of 1-4 were determined by single-crystal X-ray diffraction, NOESY spectra, ECD calculations, and biogenetic considerations. The absolute configuration of compound 3 was confirmed for the first time. Compound 5 showed moderate activity against AChE with an IC50 value of 13.9 ± 1.1 µM.

Nursing Care of 26 Infants Born to Mothers With COVID-19.

BACKGROUND: Novel coronavirus disease (COVID-19) has spread throughout the world; yet, there are few reports of neonatal cases. Thus, information about related clinical care experience is scarce. CLINICAL FINDINGS: This case report includes 26 infants admitted to the neonatal intensive care unit (NICU) of Tongji Hospital in Wuhan City who were born to mothers with suspected/confirmed COVID-19. The nursing and medical staff implemented care of these infants in strict accordance with infection control measures. INTERVENTION: Emergency measures for the prevention and control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the NICU were developed, and neonatal isolation, observation, and treatment were performed. OUTCOMES: Vital signs of the 26 infants remained stable during isolation and treatment, and no complications occurred. During the study period, neither the infants nor the nursing and medical staff were infected with SARS-CoV-2. PRACTICE RECOMMENDATIONS: Based on our strict practices, infants born to mothers with suspected/confirmed COVID-19 should receive care in a single-patient room to support infection control and provide enhanced observation. During initial contact and nursing care, increased attention should be given to the protection of infants born to mothers with suspected/confirmed COVID-19.

Improvement of Rice Agronomic Traits by Editing Type-B Response Regulators.

Type-B response regulator proteins in rice contain a conserved receiver domain, followed by a GARP DNA binding domain and a longer C-terminus. Some type-B response regulators such as RR21, RR22 and RR23 are involved in the development of rice leaf, root, flower and trichome. In this study, to evaluate the application potential of type-B response regulators in rice genetic improvement, thirteen type-B response regulator genes in rice were respectively knocked out by using CRISPR/Cas9 genome editing technology. Two guide RNAs (gRNAs) were simultaneously expressed on a knockout vector to mutate one gene. T0 transformed plants were used to screen the plants with deletion of large DNA fragments through PCR with specific primers. The mutants of CRISPR/Cas9 gene editing were detected by Cas9 specific primer in the T1 generation, and homozygous mutants without Cas9 were screened, whose target regions were confirmed by sequencing. Mutant materials of 12 OsRRs were obtained, except for RR24. Preliminary phenotypic observation revealed variations of various important traits in different mutant materials, including plant height, tiller number, tillering angle, heading date, panicle length and yield. The osrr30 mutant in the T2 generation was then further examined. As a result, the heading date of the osrr30 mutant was delayed by about 18 d, while the yield was increased by about 30%, and the chalkiness was significantly reduced compared with those of the wild-type under field high temperature stress. These results indicated that osrr30 has great application value in rice breeding. Our findings suggest that it is feasible to perform genetic improvement of rice by editing the type-B response regulators.

[Determination of Dichloromethane in Blood with Headspace Gas Chromatography and Gas Chromatography-Mass Spectrometry].

Objective: To establish a method for qualitative determination of dichloromethane (DCM) in blood by gas chromatography-mass spectrometry (GC-MS) and quantitative determination of DCM in blood by headspace gas chromatography (HS-GC), and to provide reliable support for forensic examination and analysis of poisoning or deaths caused by DCM. Methods: 0.5 mL blood sample was collected, added into headspace vial with chloroform as the internal standard, and processed by heating at 65 °C and evacuation treatment. The intermediate gas in the headspace vial was analyzed by GC-MS for qualitative validation of the method and by HS-GC for quantitative validation of the method. The method was then applied in forensic case analysis. Results: Qualitative validation of the examination method by GC-MS found that the chromatographic peak and mass spectral characteristic ions were specific in samples added with DCM, and that no interference was observed in the blank negative samples. The limit of detection (LOD) was 5 µg/mL. Quantitative method validation by HS-GC found that the chromatographic peak of DCM was well separated from those of eight other volatile compounds, with the resolution>1.5 in all cases; the lower limit of quantification (LOQ) was 20 µg/mL and good linearity was shown within the range of 20 and 1000 µg/mL, R>0.999; the intra-day test precision and inter-day test precision were good (relative standard deviation, or RSD<15% for both) and test accuracy was high (relative error, or δ<15%). With the method established in the study, DCM was detected successfully in the blood of two fatal cases caused by DCM poisoning, with the blood concentration being 470 µg/mL and 915 µg/mL, respectively. Conclusion: This method is shown to be a rapid, stable and accurate approach to the qualitative and quantitative forensic and toxicological analysis of DCM in blood in DCM poisoning cases or deaths caused by DCM.

Transcriptional regulation of human abraxas brother protein 1 expression by yin yang 1.

Abraxas brother protein 1 (ABRO1) is a subunit of the deubiquitinating enzyme BRCC36-containing isopeptidase complex and plays important roles in cellular responses to stress by interacting with its binding partners, such as ubiquitin-specific peptidase 7, p53, activating transcription factor 4, THAP-domain containing 5, and serine hydroxymethyltransferase. However, the transcriptional regulation of ABRO1 remains unexplored. In this study, we identified and characterized the core regulatory elements of the human ABRO1 gene and mapped them to the ABRO1 promoter region. Additionally, 5' rapid amplification of cDNA ends revealed that the transcriptional start site (TSS) was located -13 bp upstream from the start codon. Reporter gene, chromatin immunoprecipitation, and electrophoretic mobility shift assays demonstrated that ABRO1 transcription was regulated through cis-acting elements located in the region -89 to -59 bp upstream of the ABRO1 TSS and that these elements were targeted by yin yang 1 transcription factor (YY1). Moreover, YY1 overexpression increased human ABRO1 mRNA and protein expression, and small-interfering RNA-mediated downregulation of YY1 attenuated ABRO1 expression. These results suggested that YY1 positively regulated human ABRO1 expression by binding to cis-acting elements located in the ABRO1 TSS.

Overexpression of the homoterpene synthase gene, OsCYP92C21, increases emissions of volatiles mediating tritrophic interactions in rice.

Plant defence homoterpenes can be used to attract pest natural enemies. However, the biosynthetic pathway of homoterpenes is still unknown in rice, and the practical application of such indirect defence systems suffers from inherent limitations due to their low emissions from plants. Here, we demonstrated that the protein OsCYP92C21 is responsible for homoterpene biosynthesis in rice. We also revealed that the ability of rice to produce homoterpenes is dependent on the subcellular precursor pools. By increasing the precursor pools through specifically subcellular targeting expression, genetic transformation and genetic introgression, we significantly enhanced homoterpene biosynthesis in rice. The final introgressed GM rice plants exhibited higher homoterpene emissions than the wild type rice and the highest homoterpene emission reported so far for such GM plants even without the induction of herbivore attack. As a result, these GM rice plants demonstrated strong attractiveness to the parasitic wasp Cotesia chilonis. This study discovered the homoterpene biosynthesis pathway in rice, and lays the foundation for the utilisation of plant indirect defence mechanism in the "push-pull" strategy of integrated pest management through increasing precursor pools in the subcellular compartments and overexpressing homoterpene synthase by genetic transformation.

EDAG mediates Hsp70 nuclear localization in erythroblasts and rescues dyserythropoiesis in myelodysplastic syndrome.

During human erythroid maturation, Hsp70 translocates into the nucleus and protects GATA-1 from caspase-3 cleavage. Failure of Hsp70 to localize to the nucleus was found in Myelodysplastic syndrome (MDS) erythroblasts and can induce dyserythropoiesis, with arrest of maturation and death of erythroblasts. However, the mechanism of the nuclear trafficking of Hsp70 in erythroblasts remains unknown. Here, we found the hematopoietic transcriptional regulator, EDAG, to be a novel binding partner of Hsp70 that forms a protein complex with Hsp70 and GATA-1 during human normal erythroid differentiation. EDAG overexpression blocked the cytoplasmic translocation of Hsp70 induced by EPO deprivation, inhibited GATA-1 degradation, thereby promoting erythroid maturation in an Hsp70-dependent manner. Furthermore, in myelodysplastic syndrome (MDS) patients with dyserythropoiesis, EDAG is dramatically down-regulated, and forced expression of EDAG has been found to restore the localization of Hsp70 in the nucleus and elevate the protein level of GATA-1 to a significant extent. In addition, EDAG rescued the dyserythropoiesis of MDS patients by increasing erythroid differentiation and decreasing cell apoptosis. This study demonstrates the molecular mechanism of Hsp70 nuclear sustaining during erythroid maturation and establishes that EDAG might be a suitable therapeutic target for dyserythropoiesis in MDS patients.

Chemical food contaminants during food processing: sources and control.

With the development in international food trade, there has been emerging risks in the food chain. Food contamination can be caused by several factors in a complex food chain. This articles provides a comprehensive review of known chemical contaminants from the production of raw materials to the consumption of food products as well as prevention and control measures. Specifically, this review discusses the following topics, raw material contamination caused by environmental pollution, endogenous food contamination caused by processing methods, and cold chain system challenges in food e-commerce.

Glycerol kinase enhances hepatic lipid metabolism by repressing nuclear receptor subfamily 4 group A1 in the nucleus.

Glycerol kinase (GYK) plays a critical role in hepatic metabolism by converting glycerol to glycerol 3-phosphate in an ATP-dependent reaction. GYK isoform b is the only glycerol kinase present in whole cells, and has a non-enzymatic moonlighting function in the nucleus. GYK isoform b acts as a co-regulator of nuclear receptor subfamily 4 group A1 (NR4A1) and participates in the regulation of hepatic glucose metabolism by protein-protein interaction with NR4A1. Herein, GYK expression was found to upregulate the expression of NR4A1-mediated lipid metabolism-related genes (SREBP1C, FASN, ACACA, and GPAM) in HEK293T and L02 cells, and in mouse in vivo studies. GYK expression increased blood levels of cholesterol, triglyceride, and high-density lipoprotein cholesterol, but not low-density lipoprotein cholesterol levels. It enhanced the transcriptional activity of Nr4a1 target genes by negatively cooperating with NR4A1 and its enzymatic activity or by other undefined moonlighting functions. This enhancement was observed in both normal and diabetic mice. We also found a feed-forward regulation loop between GYK and NR4A1, serving as part of a GYK-NR4A1 regulatory mechanism in hepatic metabolism. Thus, GYK regulates the effect of NR4A1 on hepatic lipid metabolism in normal and diabetic mice, partially through the cooperation of GYK and NR4A1.

NLRP3 is dispensable for d-galactosamine/lipopolysaccharide-induced acute liver failure.

The nucleotide-binding domain and leucine-rich repeat-containing family pyrin domain containing 3 (NLRP3) inflammasome is involved in various acute and chronic liver diseases, however, it is not clear whether NLRP3 contributes to d-Galactosamine (D-GalN) plus lipopolysaccharide (LPS)-induced acute liver failure (ALF). This study aims to investigate the role of NLRP3 inflammasome in D-GalN/LPS-induced fatal hepatitis. We found that Nlrp3-/- and WT mice showed similar mortality against a lethal dose of D-GalN/LPS treatment. Serum ALT and AST levels, as well as liver necrosis area and hepatocyte apoptosis, were not significantly different between Nlrp3-/- and WT mice at 6 h after D-GalN/LPS injection. Moreover, the numbers of intrahepatic F4/80+ cells and Ly6G+ cells were comparable in two genotype mice following D-GalN/LPS treatment. Besides, Nlrp3-/- mice had reduced IL-1ß levels but similar TNF-α, IL-6, and MCP-1 levels compared with WT mice upon D-GalN/LPS administration. Our findings revealed that NLRP3 ablation does not protect mice from D-GalN/LPS-induced fatal hepatitis and has a marginal effect on intrahepatic inflammatory response upon D-GalN/LPS treatment. This suggests that NLRP3 inflammasome does not appear to be a major contributor to D-GalN/LPS-induced ALF.