Garlic oil supplementation blocks inflammatory pyroptosis-related acute lung injury by suppressing the NF-κB/NLRP3 signaling pathway via H2S generation.

Acute lung injury (ALI) is a major cause of acute respiratory failure with a high morbidity and mortality rate, and effective therapeutic strategies for ALI remain limited. Inflammatory response is considered crucial for the pathogenesis of ALI. Garlic, a globally used cooking spice, reportedly exhibits excellent anti-inflammatory bioactivity. However, protective effects of garlic against ALI have never been reported. This study aimed to investigate the protective effects of garlic oil (GO) supplementation on lipopolysaccharide (LPS)-induced ALI models. Hematoxylin and eosin staining, pathology scores, lung myeloperoxidase (MPO) activity measurement, lung wet/dry (W/D) ratio detection, and bronchoalveolar lavage fluid (BALF) analysis were performed to investigate ALI histopathology. Real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay were conducted to evaluate the expression levels of inflammatory factors, nuclear factor-κB (NF-κB), NLRP3, pyroptosis-related proteins, and H2S-producing enzymes. GO attenuated LPS-induced pulmonary pathological changes, lung W/D ratio, MPO activity, and inflammatory cytokines in the lungs and BALF. Additionally, GO suppressed LPS-induced NF-κB activation, NLRP3 inflammasome expression, and inflammatory-related pyroptosis. Mechanistically, GO promoted increased H2S production in lung tissues by enhancing the conversion of GO-rich polysulfide compounds or by increasing the expression of H2S-producing enzymes in vivo. Inhibition of endogenous or exogenous H2S production reversed the protective effects of GO on ALI and eliminated the inhibitory effects of GO on NF-κB, NLRP3, and pyroptotic signaling pathways. Overall, these findings indicate that GO has a critical anti-inflammatory effect and protects against LPS-induced ALI by suppressing the NF-κB/NLRP3 signaling pathway via H2S generation.

Vanadium nitride@carbon nanofiber composite: Synthesis, cascade enzyme mimics and its sensitive and selective colorimetric sensing of superoxide anion.

Nanozymes featuring with favorable activity, good stability and easy scale-up production, are promising to replace natural enzymes for various applications. However, it remains a challenge to explore the cascade reactions of multi-enzyme mimics, aiming at synergistic catalysis for various applications. Herein, vanadium nitride nanoparticles deposited on carbon nanofibers (VN@CNFs) composite was facilely prepared by typical electrospinning route with subsequently ammonia reduction process. The nanocomposite showed excellent peroxidase (POD)-like and superoxide dismutase (SOD)-like activities. Additionally, their catalytic mechanisms were systematically researched. Coupling of SOD-like with POD-like as cascade enzyme, a selective and sensitive colorimetric detection of superoxide anion (O2•-) was explored, which has two linear parts, 0.05-30 µM and 30-250 µM O2•- with the LOD of 0.0167 µM (S/N = 3). The as-proposed method was applicable to practical samples detection with satisfactory accuracy and recovery. Therefore, the VN@CNFs composite shows great prospect in biosensing, superoxide anion removal and biocatalysis.

The combination of nicotinamide mononucleotide and lycopene prevents cognitive impairment and attenuates oxidative damage in D-galactose induced aging models via Keap1-Nrf2 signaling.

Aging is referred to progressive dysfunction of body organs, including the brain. This study aims to explore the anti-aging effect of combing nicotinamide mononucleotide (NMN) and lycopene (Lyco) (NMN + Lyco) on aging rats and senescent PC12 cells. Both in vivo and in vitro aging models were established using D-galactose (D-gal). The combination showed a trend to superiority over monotherapy in preventing aging in vivo and in vitro. Morris water maze test showed that NMN + Lyco effectively improved the ability of spatial location learning and memory of aging model rats. NMN + Lyco mitigated the oxidative stress of rat brains, livers, and PC12 cells by elevating the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), GSH, as well as total antioxidant capacity (T-AOC), and reducing malondialdehyde (MDA) content. CCK-8 assay, senescence-associated ß-galactosidase staining, and flow cytometer confirmed the cellular senescence of PC12 cells after exposing D-gal, and indicated the anti-senescence effect of NMN + Lyco in vitro. Moreover, NMN + Lyco effectively down-regulated the expressions of p53, p21, and p16 (senescence-related genes), and activated Keap1-Nrf2 signaling in both in vivo and in vitro aging models. In total, NMN + Lyco protected rats and PC12 cells from cognitive impairment and cellular senescence induced by D-gal, of which effects might be linked to the reduction of oxidative stress and the activation of Keap1-Nrf2 signaling.

Comparative transcriptome analysis uncovers different heat stress responses in heat-resistant and heat-sensitive jujube cultivars.

Jujube (Ziziphus jujuba Mill.) is an economically and agriculturally significant fruit crop and is widely cultivated throughout the world. Heat stress has recently become a primary abiotic stressor limiting the productivity and growth of jujube, as well as other crops. There are few studies, however, that have performed transcriptome profiling of jujube when it is exposed to heat stress. In this study, we observed the physiochemical changes and analyzed gene expression profiles in resistant jujube cultivar 'HR' and sensitive cultivar 'HS' subjected to heat stress for 0, 1, 3, and 5d. Twenty-four cDNA libraries from 'HR' and 'HS' leaves were built with a transcriptome assay. A total of 6887 and 5077 differentially expressed genes were identified in 'HR' and 'HS' after 1d, 3d, and 5d of heat stress compared with the control treatment, GO and KEGG enrichment analysis revealed that some of the genes were highly enriched in oxidation-reduction process, response to stress, response to water deprivation, response to heat, carbon metabolism, protein processing in endoplasmic reticulum, and plant hormone signal transduction and may play vital roles in the heat stress response in jujube plants. Differentially expressed genes were identified in the two cultivars, including heat shock proteins, transcriptional factors, and ubiquitin-protein ligase genes. And the expression pattern of nine genes was also validated by qRT-PCR. These results will provide useful information for elucidating the molecular mechanism underlying heat stress in different jujube cultivars.

Arabidopsis PEAPODs function with LIKE HETEROCHROMATIN PROTEIN1 to regulate lateral organ growth.

In higher plants, lateral organs are usually of determinate growth. It remains largely elusive how the determinate growth is achieved and maintained. Previous reports have shown that Arabidopsis PEAPOD (PPD) proteins suppress proliferation of dispersed meristematic cells partly through a TOPLESS corepressor complex. Here, we identified a new PPD-interacting partner, LIKE HETEROCHROMATIN PROTEIN1 (LHP1), using the yeast two-hybrid system, and their interaction is mediated by the chromo shadow domain and the Jas domain in LHP1 and PPD2, respectively. Our genetic data demonstrate that the phenotype of ppd2 lhp1 is more similar to lhp1 than to ppd2, indicating epistasis of lhp1 to ppd2. Microarray analysis reveals that PPD2 and LHP1 can regulate expression of a common set of genes directly or indirectly. Consistently, chromatin immunoprecipitation results confirm that PPD2 and LHP1 are coenriched at the promoter region of their targets such as D3-TYPE CYCLINS and HIGH MOBILITY GROUP A, which are upregulated in ppd2, lhp1 and ppd2 lhp1 mutants, and that PPDs mediate repressive histone 3 lysine-27 trimethylation at these loci. Taken together, our data provide evidence that PPD and LHP1 form a corepressor complex that regulates lateral organ growth.

Study on the homology of the genomes of tetraploid Asiatic lilies (Lilium) using FISH.

Asiatic lily cultivars, bred by hybridization and (or) chromosome doubling of species of section Sinomartagon of Lilium, are diploid, triploid, or tetraploid, but the homology of the genomes among species of section Sinomartagon and Asiatic lilies remains unclear. In the present research, two tetraploid Asiatic cultivars were analyzed, using 45S rDNA as probe, for their FISH karyotypes and their chromosomal association, anaphase I, telophase II, and pollen viability were surveyed to assess the multivalent segregation. Chromosomal assortment of six progenies of the two tetraploid cultivars were also investigated. The results showed that the tetraploid cultivars had similar FISH karyotypes, they predominantly formed multivalents, and these were equally separated because their anaphase I, telophase II, and pollen viability were similar to those of diploid species. Apart from minor variations, FISH karyotypes of progenies were similar to each other and to their parents. Based on these results and considering the high crossability among species of section Sinomartagon and (or) Asiatic lilies, we concluded that species of section Sinomartagon and their resulting cultivars share a common genome; thus, polyploidy Asiatic lilies are autopolyploid.

Global analysis of cis-natural antisense transcripts and their heat-responsive nat-siRNAs in Brassica rapa.

BACKGROUND: Brassica rapa includes several important leaf vegetable crops whose production is often damaged by high temperature. Cis-natural antisense transcripts (cis-NATs) and cis-NATs-derived small interfering RNAs (nat-siRNAs) play important roles in plant development and stress responses. However, genome-wide cis-NATs in B. rapa are not known. The NATs and nat-siRNAs that respond to heat stress have never been well studied in B. rapa. Here, we took advantage of RNA-seq and small RNA (sRNA) deep sequencing technology to identify cis-NATs and heat responsive nat-siRNAs in B. rapa. RESULTS: Analyses of four RNA sequencing datasets revealed 1031 cis-NATs B. rapa ssp. chinensis cv Wut and B. rapa ssp. pekinensis cv. Bre. Based on sequence homology between Arabidopsis thaliana and B. rapa, 303 conserved cis-NATs in B. rapa were found to correspond to 280 cis-NATs in Arabidopsis; the remaining 728 novel cis-NATs were identified as Brassica-specific ones. Using six sRNA libraries, 4846 nat-siRNAs derived from 150 cis-NATs were detected. Differential expression analysis revealed that nat-siRNAs derived from 12 cis-NATs were responsive to heat stress, and most of them showed strand bias. Real-time PCR indicated that most of the transcripts generating heat-responsive nat-siRNAs were upregulated under heat stress, while the transcripts from the opposite strands of the same loci were downregulated. CONCLUSIONS: Our results provide the first subsets of genome-wide cis-NATs and heat-responsive nat-siRNAs in B. rapa; these sRNAs are potentially useful for the genetic improvement of heat tolerance in B. rapa and other crops.

A genome-wide siRNA screen reveals multiple mTORC1 independent signaling pathways regulating autophagy under normal nutritional conditions.

Autophagy is a cellular catabolic mechanism that plays an essential function in protecting multicellular eukaryotes from neurodegeneration, cancer, and other diseases. However, we still know very little about mechanisms regulating autophagy under normal homeostatic conditions when nutrients are not limiting. In a genome-wide human siRNA screen, we demonstrate that under normal nutrient conditions upregulation of autophagy requires the type III PI3 kinase, but not inhibition of mTORC1, the essential negative regulator of starvation-induced autophagy. We show that a group of growth factors and cytokines inhibit the type III PI3 kinase through multiple pathways, including the MAPK-ERK1/2, Stat3, Akt/Foxo3, and CXCR4/GPCR, which are all known to positively regulate cell growth and proliferation. Our study suggests that the type III PI3 kinase integrates diverse signals to regulate cellular levels of autophagy, and that autophagy and cell proliferation may represent two alternative cell fates that are regulated in a mutually exclusive manner.

[Expression of nm23 H(1) gene in childhood acute lymphoblastic leukemia and the relationship between nm23 H(1) expression and immunophenotype].

OBJECTIVE: To study the expression of nm23-H(1) gene in children with acute lymphoblastic leukemia (ALL) and the relationship between nm23-H(1) expression and immunophenotype. METHODS: nm23-H(1) expression was measured by semiquantitative RT-PCR in children with ALL (newly diagnosed, n = 40; remission, n = 32; relapse, n = 16; refractory, n = 3). Twenty normal children served as the control group. The relationship between nm23-H(1) expression and immunophenotype was evaluated. RESULTS: The expression of nm23-H(1) in the newly diagnosed ALL group was significantly higher than that in the control (p<0.01) and the remission groups (p<0.01). There was no difference in the nm23-H(1) expression between the remission and the control groups. The expression of nm23-H(1) in the relapse group was significantly higher than that in the control (p<0.01) and the remission groups (p<0.01), and similar to that in the newly diagnosed ALL group. The three children with refractory ALL had higher nm23-H(1) expression. Both the positive rate and expression of nm23-H(1) in children with T-lineage ALL were higher than in children with B-lineage ALL (p<0.05). CONCLUSIONS: The expression level of nm23-H(1) varies with the stages of ALL. Newly diagnosed, relapsed and refractory ALL children have higher nm23-H(1) expression. High nm23-H(1) expression may be associated with a poor prognosis and relapse. A higher expression of nm23-H(1) in children with T-ALL may be contributed to a low remission rate and a poor prognosis.