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Vascular endothelial cell senescence is a leading cause of age-associated diseases and cardiovascular diseases. Interventions and therapies targeting endothelial cell senescence and dysfunction would have important clinical implications. This study evaluated the effect of 10 resveratrol analogues, including pterostilbene (Pts) and its derivatives, against endothelial senescence and dysfunction. All the tested compounds at the concentrations from 10−9 M to 10−6 M did not show cytotoxicity in endothelial cells by MTT assay. Among the 10 resveratrol analogues, Pts and Pts nicotinate attenuated the expression of senescence-associated β-galactosidase, downregulated p21 and p53, and increased the production of nitric oxide (NO) in both angiotensin II – and hydrogen peroxide – induced endothelial senescence models. In addition, Pts and Pts nicotinate elicited endothelium-dependent relaxations, which were attenuated in the presence of endothelial NO synthase (eNOS) inhibitor L-NAME or sirtuin 1 (SIRT1) inhibitor sirtinol. Pts and Pts nicotinate did not alter SIRT1 expression but enhanced its activity. Both Pts and Pts nicotinate have high binding activities with SIRT1, according to surface plasmon resonance results and the molecular docking analysis. Inhibition of SIRT1 by sirtinol reversed the anti-senescent effects of Pts and Pts nicotinate. Moreover, Pts and Pts nicotinate shared similar ADME (absorption, distribution, metabolism, excretion) profiles and physiochemical properties. This study suggests that the Pts and Pts nicotinate ameliorate vascular endothelial senescence and elicit endothelium-dependent relaxations via activation of SIRT1. These two compounds may be potential drugs for the treatment of cardiovascular diseases related to endothelial senescence and dysfunction.

Potato virus X (PVX) is a widely distributed viral pathogen that causes significant losses in potato production by co-infecting with potato virus Y or potato virus A. In this study, the resistance of 23 potato cultivars to PVX was dissected in detail using a PVX infectious clone containing a yellow fluorescent protein (YFP). Among them, four potato cultivars (Longshu-3, Eugene, Atlantic and Waiyin-2) were found to carry an Rx gene that confers extreme resistance to PVX; one cultivar (Waiyin-1) displayed partial resistance and was able to delay PVX infection by ~ 5 days; while the rest eighteen potato cultivars were susceptible to PVX. Moreover, we found that the replication but not cell-to-cell or long-distance movement of PVX was inhibited in Waiyin-1. Finally, we determined that the expression of pathogenesis-related (PR) genes in Waiyin-1 was not triggered by PVX infection at early infection stage, whereas they were triggered in the Rx-carrying cultivar Atlantic during this period of time. In conclusion, our results confirm that Rx is a major type of resistance gene in potato cultivars in the Northeast part of China. Furthermore, the possible mechanism underlying Waiyin-1 resistance to PVX is discussed.

Hynobius amjiensis was considered as one of the 29 most threatened amphibian in China. To effectively conserve, manage and recover the population of this critically endangered species, 33 single nucleotide polymorphism (SNP) markers were developed using double digest restriction-site associated DNA (ddRAD) sequencing. The minor allele frequency per locus ranged from 0.0161 to 0.5000. The observed heterozygosity and expected heterozygosity varied from 0.0323 to 0.6667 (average 0.3303) and from 0.0317 to 0.5000 (average 0.2772), respectively. The inbreeding coefficient value ranged between − 0.3315 and 0.0000. No significant deviation from Hardy-Weinberg equlibrium (P > 0.05) were found in all loci. These novel SNPs will be helpful for the population genetic assessment and conservation of H. amjiensis.

Plant endophytic bacteria colonize the internal tissues of plants and interact with plants closely. The past two decades have witnessed the increasing application of next-generation 16S rRNA gene sequencing in the investigation of bacterial communities. However, deciphering plant endo-bacterial communities by this method is difficult because of the co-amplification of massive plant organellar DNAs with bacterial 16S. Here, we designed polymerase chain reaction (PCR) primer sets, including 799F/1107R, 322F/796R, and 322F-Dr/796Rs (primer pair 322F/796R with a penultimate-base substitution in 322F), that can specifically amplify bacterial 16S from plant total DNAs. We computationally and experimentally evaluated the specificity, coverage, and accuracy of the newly designed primer sets. Both 799F/1107R and 322F-Dr/796Rs produced plant DNA-free 16S amplicon libraries or reduced plant DNA contamination to lower than 5% for the plant materials with extremely-low-abundance bacterial communities. The primer set 322F-A/796R was used through absolute quantitative PCR to quantitate the population size of rice leaf or root endo-bacteriome, which revealed 106–107 and 109–1010 bacteria per gram fresh weight, respectively. These 16S primer sets and amplification methods enable the simple and inexpensive next-generation sequencing and quantification of plant endo-bacteriome, which will significantly advance studies on the plant-related microbiome.

Along with the rapid development of nanotechnology, the bio-safety assessment of nanotechnology products, including nanomaterials, becomes more and more important. Nematode Caenorhabditis elegans (C. elegans) is a valuable model organism that has been widely used in the field of biology because of their excellent advantages, including low cost, small size, short life span, and highly conservative genomes with vertebral animals. In recent years, the number of nanotoxicological researches using C. elegans is persistently growing. According to these available studies, this review classified the adverse effects of nanomaterials in C. elegans into systematic, cellular and molecular toxicity, and focused on summarizing and analyzing the underlying mechanisms of metal, metal oxide and non-metallic nanomaterials causing toxic effects in C. elegans. The findings in this review provided an insight in further studies on assessing bio-safety of nanomaterials in the ecosystem using C. elegans. This article is protected by copyright. All rights reserved.

Background The serine carboxypeptidase-like protein (SCPL) family plays a vital role in stress response, growth, development and pathogen defense. However, the identification and functional analysis of SCPL gene family members have not yet been performed in wheat. Results In this study, we identified a total of 210 candidate genes encoding SCPL proteins in wheat. According to their structural characteristics, it is possible to divide these members into three subfamilies: CPI, CPII and CPIII. We uncovered a total of 209 TaSCPL genes unevenly distributed across 21 wheat chromosomes, of which 65.7% are present in triads. Gene duplication analysis showed that ~ 10.5% and ~ 64.8% of the TaSCPL genes are derived from tandem and segmental duplication events, respectively. Moreover, the Ka/Ks ratios between duplicated TaSCPL gene pairs were lower than 0.6, which suggests the action of strong purifying selection. Gene structure analysis showed that most of the TaSCPL genes contain multiple introns and that the motifs present in each subfamily are relatively conserved. Our analysis on cis-acting elements showed that the promoter sequences of TaSCPL genes are enriched in drought-, ABA- and MeJA-responsive elements. In addition, we studied the expression profiles of TaSCPL genes in different tissues at different developmental stages. We then evaluated the expression levels of four TaSCPL genes by qRT-PCR, and selected TaSCPL184-6D for further downstream analysis. The results showed an enhanced drought and salt tolerance among TaSCPL184-6D transgenic Arabidopsis plants, and that the overexpression of the gene increased proline and decreased malondialdehyde levels, which might help plants adapting to adverse environments. Our results provide comprehensive analyses of wheat SCPL genes that might work as a reference for future studies aimed at improving drought and salt tolerance in wheat. Conclusions We conducte a comprehensive bioinformatic analysis of the TaSCPL gene family in wheat, which revealing the potential roles of TaSCPL genes in abiotic stress. Our analysis also provides useful resources for improving the resistance of wheat.

Stabilized fertilizers that contain nitrification inhibitors and/or urease inhibitors are widely used in China. A pot experiment was conducted to analyze soil enzymatic characteristics related to carbon and nitrogen turnover and metabolism under the use of rice straw and stabilized fertilizer. Results showed that stabilized fertilizer exhibited the highest yield production, panicle numbers, and above-ground biomass. Compared with urea treatment with straw, adding inhibitors reduced soil organic carbon and the enzyme activity related to acquisition of carbon, but increased soil organic carbon accumulation, rice yield, and above-ground biomass. Stabilized fertilizer increased protease activity; however, it decreased N-acetyl-β-glucosaminide. Addition of straw significantly increased dissolved organic and microbial biomass carbon or nitrogen, as well as the enzyme activities of α-D-glucosidase, β-D-glucosidase, β-N-acetyl-glucosidase, and cellulase at the seedling and tillering stages. The principal components analysis showed that the synthesis of extracellular enzyme related to carbon and nitrogen acquiring act as a proxy for straw decomposing under nitrogen conditions. The combination delayed the release of ammonia, which affected the carbon and nitrogen coupling by microbial organisms. These results demonstrated a relationship between soil carbon and nitrogen dynamics and soil enzymes in different fertilization management.

Numerous studies of relationship between epigenomic features have focused on their strong correlation across the genome, likely because such relationship can be easily identified by many established methods for correlation analysis. However, two features with little correlation may still colocalize at many genomic sites to implement important functions. There is no bioinformatic tool for researchers to specifically identify such feature pairs. Here, we develop a method to identify feature pairs in which two features have maximal colocalization minimal correlation (MACMIC) across the genome. By MACMIC analysis of 3306 feature pairs in 16 human cell types, we reveal a dual role of CCCTC-binding factor (CTCF) in epigenetic regulation of cell identity genes. Although super-enhancers are associated with activation of target genes, only a subset of super-enhancers colocalized with CTCF regulate cell identity genes. At super-enhancers colocalized with CTCF, CTCF is required for the active marker H3K27ac in cell types requiring the activation, and also required for the repressive marker H3K27me3 in other cell types requiring repression. Our work demonstrates the biological utility of the MACMIC analysis and reveals a key role for CTCF in epigenetic regulation of cell identity. The code for MACMIC is available at https://github.com/bxia888/MACMIC.

Upon infection with insect-borne microbial pathogens, plants are exposed to two types of damage simultaneously. Over the past decade, numerous molecular studies have been conducted to understand how plants respond to pathogens or herbivores. However, investigations of host responses typically focus on a single stress and are performed under static laboratory conditions. In this review, we highlight research that sheds light on how plants deploy broad-spectrum mechanisms against both vector-borne pathogens and insect vectors. Among the host genes involved in multistress resistance, many are involved in innate immunity and phytohormone signaling (especially jasmonate and salicylic acid). The potential for genome editing or chemical modulators to fine-tune crop defensive signaling, to develop sustainable methods to control insect-borne diseases, is discussed.

Pigeon paramyxovirus type 1 (PPMV-1) is a globally distributed, virulent member of the avian paramyxovirus type-1. The PPMV-1–associated disease poses a great threat to the pigeon industry. The innate immune response is crucial for antiviral infections and revealing the pathogenic mechanisms of PPMV-1. In this study, we evaluated the pathogenicity of a PPMV-1 strain LHLJ/110822 in one-month-old domestic pigeons, as well as the host immune responses in PPMV-1–infected pigeons. We observed typically clinical sign in infected pigeons by 3 dpi. The morbidity rate and the mortality in pigeons inoculated with the PPMV-1 strain were up to 100% and 30%, respectively. The virus could replicate in all of the examined tissues, namely trachea, lung, liver, spleen, and bursa of Fabricius. In addition, the infected pigeons had developed anti-PPMV-1 antibodies as early as 8 dpi; and the antibody level increased over the time in this study. The expression level of toll-like receptor (TLR) 2, TLR3 TLR15, IFN-γ, and IL-6 were significantly upregulated by the PPMV-1 infection in some tissues of pigeons. By contrast, PPMV-1 infection results in downregulation of IL-18 expression in most of investigated tissues except for bursa of Fabricius in this study. The current results confirmed that this virus could replicate in pigeons and induce host immune responses, then leading to produce serum antibody titers. Meanwhile, the PPMV-1 infection induces strong innate immune responses and intense inflammatory responses at early stage in pigeon which may associate with the viral pathogenesis.

The occurrence of high-level tigecycline resistance tet(X) variant genes represents a new transferable resistance crisis to food safety and human health. Here, we investigated the abundance of tet(X)-variant genes [tet(X), tet(X1) to tet(X6)] in 33 samples collected from layer manures, manured/un-manured soils, and corresponding lettuce from three provinces in China. The results showed the occurrence of tet(X)/(X2), tet(X3), and tet(X4) in 24 samples. The detection rate of tet(X)/(X2) (23/24) is higher than that of tet(X3) (7/24) and tet(X4) (2/24), and tet(X)/tet(X2) and tet(X3) were found to be enriched and more abundant in most manured soil and several lettuce samples from manured soils than that from manure samples. Twenty six tigecycline-resistant bacteria were isolated, and tet(X)-variant genes were found to be disseminated not only by bacterial clone spreading but also via multidrug resistance plasmids. The total concentrations of tet(X)-variant genes showed significantly positive correlations (R = 0.683, p < 0.001) with ISCR2. Two veterinary tetracyclines (tetracycline and oxytetracycline) and other classes of antimicrobials (enrofloxacin, azithromycin, thiamphenicol, and florfenicol) showed significant correlations with the total concentrations of tet(X)-variant genes (R = 0.35-0.516, p < 0.05). The findings indicate the transmission of tet(X)-variant genes from layer manures to their receiving environmental soils and lettuce and highlight the contribution of veterinary antimicrobials to the spread of tet(X)-variant genes.

Purpose: In this study, we have undertaken the whole proteomic analysis and got a better understanding of biological processes involved in the development and progression of ccRCC. We hope promising biomarkers can be uncovered to facilitate early diagnosis, predict the prognosis and progression, more importantly, to be applied as potential therapeutic targets. Experimental design: Fresh frozen tissue samples were surgically resected from patients with local or locally advanced ccRCC. Trypsin digested proteins were analyzed using TMT-based LC-MS/MS proteomic approach, followed by bioinformatic analysis. A potential prognostic marker FMNL1 was chosen to be validated in TCGA_KIRC datasets (n=525 and 72), further validation sets (n=10 and 10) and expanded validation sets (n=81 and 16). The effects of FMNL1 on proliferation, migration and invasion were determined by colony formation, wound healing, and transwell assays in 786-O and Caki-1 cells in vitro study. Results: A total of 657 differentially expressed proteins were identified and quantified between ccRCC and adjacent normal tissues (p-value2 or

A pot experiment was used to explore the distribution of fertilizer N and agronomic effects in a paddy soil-rice (Oryza sativa L.) system. Five treatments were set: without nitrogen, straw and inhibitor (C), urea (U), urea + straw (US), urea + urease + nitrification inhibitor (UI) and urea + urease + nitrification inhibitor + straw (UIS). Soil and urea-derived microbial biomass N increased significantly in US and UIS compared with straw-free treatments at seedling and tillering, indicating that biotic process play an important role in the retention of fertilizer N with straw addition. About 10% urea-N was recovered as fixed ammonium (FA) at seedling stage, subsequently released at tillering and maturation regardless of treatments, which emphasizes the importance of FA in the retention and supply of fertilizer N in paddy soils. Compared with U, rice yield and N uptake in US decreased by 7.8% and 25.2% respectively, while inhibitors (UIS) alleviated the reduction by 16.4% and 31.6%. The current research indicated UIS is recommended as the most appropriate management strategy in paddy soils of Northeast China based on N dynamics. But the economic effect as well as the field-scale validation need to be further evaluated.

Shigella spp. are water-borne pathogens responsible for mild to severe cases bacilli dysentery all around the world known as Shigellosis. The progressively increasing of antibiotic resistance among Shigella calls for developing and establishing novel alternative therapeutic methods. The present study aimed to evaluate a novel phage cocktail of lytic phages against extended spectrum beta lactamase isolates of Shigella species in an aquatic environment. The phage cocktail containing six novel Shigella specific phages showed a broad host spectrum. The cocktail was very stable in aquatic environment. The cocktail resulted in about 99% decrease in the bacterial counts in the contaminated water by several species and strains of Shigella such as Shigella sonnei, Shigella flexneri and Shigella dysenteriae. Achieving such a high efficiency in this in-vitro study demonstrates a high potential for in-vivo and in-situ application of this phage cocktail as a bio-controlling agent against Shigella spp. contamination and infections.

The present experiment was conducted to evaluate the effect of enzymatically treated Artemisia annua L. (EA) on intestinal digestive function and immune capacity in weaned pigs. Firstly, a total of 300 21-day-old piglets were randomly allotted to five groups, including CON, EA1, EA2, EA3, and EA4 groups (basal diet supplemented with 0, 0.5, 1, 2, 4 g/kg EA, respectively). At 50 days of age, the results showed that pigs in the EA3 group presented significant improvements (p

Rice stripe virus (RSV) is the causative agent of rice stripe disease and is completely dependent on insect vectors for its plant-to-plant transmission. Laodelphax striatellus is the major insect vector for RSV. In this study, we explored the interactions between RSV infection and L. striatellus autophagy, a potential intrinsic antiviral mechanism in insects. We found that L. striatellus autophagic activity did not affect RSV infection; however, the autophagy-related-8 (Atg8) gene significantly enhanced virus infection. During RSV initial infection within the L. striatellus midgut, silencing of Atg8 expression significantly decreased the phosphorylation of c-Jun N-terminal kinase (p-JNK); however, when RSV infection is absent, silencing of Atg8 did not alter p-JNK levels. These results indicated that Atg8 might activate the JNK machinery by allowing more virus infection into cells. We further revealed that Atg8-deficiency significantly decreased RSV accumulation on the surface of the insect midgut epithelial cells, suggesting a receptor trafficking function of the γ-aminobutyric acid receptor-associated protein family. Using the RSV ovary entry as a model, in which vitellogenin receptor (VgR) mediates RSV cell entry, we clarified that Atg8-deficiency decreased the abundance of VgR localizing on the cytomembrane and disturbed the attachment of RSV in the germarium zones. Collectively, these results revealed an autophagy-independent function of L. striatellus Atg8 that enhances RSV initial infection by increasing virus attachment on the infection sites.

Zinc finger protein 143 (ZNF143) belongs to the zinc finger protein family and possesses transcription factor activity by binding sequence-specific DNA. The exact biological role of ZNF143 in hepatocellular carcinoma (HCC) has not been investigated. Here we report that ZNF143 is overexpressed in HCC tissues and its overexpression correlates with poor prognosis. Gain- and loss-of-function experiments showed that ZNF143 promoted HCC cell proliferation, colony formation, and tumor growth in vitro and in vivo. ZNF143 accelerated HCC cell-cycle progression by activating cell division cycle 6 (CDC6). Mechanistically, ZNF143 promoted expression of CDC6 by directly activating transcription of histone demethylase mineral dust–induced gene (MDIG), which in turn reduced H3K9me3 enrichment in the CDC6 promoter region. Consistently, ZNF143 expression correlated significantly with MDIG and CDC6 expression in HCC. Collectively, we propose a model for a ZNF143–MDIG–CDC6 oncoprotein axis that provides novel insight into ZNF143, which may serve as a therapeutic target in HCC. Significance: These findings describe the mechanism by which ZNF143 promotes HCC proliferation and provide important clues for exploring new targets and strategies for clinical treatment of human liver cancer.

At present, anti-CD20 monoclonal antibody treatments targeting systemic lupus erythematosus (SLE) are complex, variable, and often have disappointing outcomes. High levels of programmed cell death-1 (PD-1) and its ligands (PD-L1, PD-L2) or CD80/CD86 on B cell surfaces are markers of increased B cell activity. However, their expression levels on CD19+CD20+/− B cells and their clinical significance for SLE dynamics have not been carefully investigated. Flow cytometry was used to detect the expression levels of PD-1, PD-L1, PD-L2, CD80, and CD86 on CD19+CD20+/− B cells in peripheral blood from SLE patients and healthy controls (HCs). The amount of anti-dsDNA and immunoglobin G (IgG) secreted by CD19+CD20+/− B cells was measured by enzyme-linked immunosorbent assay. CD19+CD20− B cell frequency was significantly higher in SLE patients than in HCs (P

Deposition of hyperphosphorylated and aggregated tau protein in the central nervous system is characteristic of Alzheimer disease and other tauopathies. Tau is subject to O-linked N-acetylglucosamine (O-GlcNAc) modification, and O-GlcNAcylation of tau has been shown to influence tau phosphorylation and aggregation. Inhibition of O-GlcNAcase (OGA), the enzyme that removes O-GlcNAc moieties, is a novel strategy to attenuate the formation of pathologic tau. Here we described the in vitro and in vivo pharmacological properties of a novel and selective OGA inhibitor, MK-8719. In vitro, this compound is a potent inhibitor of the human OGA enzyme with comparable activity against the corresponding enzymes from mouse, rat, and dog. In vivo, oral administration of MK-8719 elevates brain and peripheral blood mononuclear cell O-GlcNAc levels in a dose-dependent manner. In addition, positron emission tomography imaging studies demonstrate robust target engagement of MK-8719 in the brains of rats and rTg4510 mice. In the rTg4510 mouse model of human tauopathy, MK-8719 significantly increases brain O-GlcNAc levels and reduces pathologic tau. The reduction in tau pathology in rTg4510 mice is accompanied by attenuation of brain atrophy, including reduction of forebrain volume loss as revealed by volumetric magnetic resonance imaging analysis. These findings suggest that OGA inhibition may reduce tau pathology in tauopathies. However, since hundreds of O-GlcNAcylated proteins may be influenced by OGA inhibition, it will be critical to understand the physiologic and toxicological consequences of chronic O-GlcNAc elevation in vivo. SIGNIFICANCE STATEMENT: MK-8719 is a novel, selective, and potent O-linked N-acetylglucosamine (O-GlcNAc)-ase (OGA) inhibitor that inhibits OGA enzyme activity across multiple species with comparable in vitro potency. In vivo, MK-8719 elevates brain O-GlcNAc levels, reduces pathological tau, and ameliorates brain atrophy in the rTg4510 mouse model of tauopathy. These findings indicate that OGA inhibition may be a promising therapeutic strategy for the treatment of Alzheimer disease and other tauopathies.

Conversion between cell types, e.g., by induced expression of master transcription factors, holds great promise for cellular therapy. Our ability to manipulate cell identity is constrained by incomplete information on cell identity genes (CIGs) and their expression regulation. Here, we develop CEFCIG, an artificial intelligent framework to uncover CIGs and further define their master regulators. On the basis of machine learning, CEFCIG reveals unique histone codes for transcriptional regulation of reported CIGs, and utilizes these codes to predict CIGs and their master regulators with high accuracy. Applying CEFCIG to 1,005 epigenetic profiles, our analysis uncovers the landscape of regulation network for identity genes in individual cell or tissue types. Together, this work provides insights into cell identity regulation, and delivers a powerful technique to facilitate regenerative medicine., Identification of genes that determine and regulate cell identity remains challenging. Here, the authors use machine learning to identify cell identity genes and master regulator transcription factors based on gene expression profiles and histone modifications.

The milk fat globule membrane (MFGM) is a complex, highly conserved structure surrounding fat droplets secreted into mammalian milk. This study evaluated the impact of MFGM on Lactobacillus rhamnosus GG (LGG). MFGM-10 (2.5 g/L, 5 g/L, and 10 g/L) did not affect LGG growth in MRS medium but enhanced the ability of LGG to survive in the presence of 0.5% porcine bile. In the presence of MFGM-10 (5 g/L) and bile (0.5%), there were less complex polysaccharides in the media and less capsular polysaccharides associated with the LGG cells compared to the bile exposure alone (p < 0.05). The expression of four EPS genes was modulated by bile stress and MFGM. Biofilm thickness was increased (p < 0.05) during bile stress with MFGM compared to other treatments. Furthermore, MFGM increased LGG survival during transit in the murine GI tract. Future experiments will determine the impact of MFGM on LGG probiotic functionality.

Lateral branches (LBs) pruning is performed frequently to keep the tomato plants in optimal growth conditions. However, the suitable pruning length of LBs, as well as the physiological and molecular mechanisms of pruning length on plant growth regulation remains elusive in tomato. The effects of pruning length of LBs from 0 to 20 cm on vegetative growth, reproductive growth, labor costs, hormone metabolism and genes transcripts were evaluated in an indeterminate type tomato cultivar. By comprehensive analysis, we provided evidence that pruning length of LBs at about 6–7 cm was suitable for plant growth, high yield, and low labor costs in tomato production. For mechanisms, appropriate extension of pruning length of LBs increased indole acetic acid (IAA) concentrations in root, which promoted the biosynthesis and upward transport of inactive cytokinins (CKs), as well as root development. Meanwhile, existence of LBs inhibited the auxin outflow of the lower flower stalks by regulating transcripts of AUX1 and PIN. Then, the enhanced concentrations of IAA and CKs in ovary could promote fruit swelling. Additionally, pruning length of LBs also influenced the leaf senescence to control photosynthesis. Taken together, we highlight that pruning length of LBs influence auxin and cytokinins homeostasis in relation to growth and yield in tomato plants.

Background Alzheimer’s disease (AD) is a neurodegenerative disease that primarily manifests as progressive memory loss and cognitive impairment. Traditional herbal medicines may be helpful in the discovery of new anti-AD drugs. Studies have shown that Ferula assafoetida has neuroprotective and memory-enhancing effects, which may be beneficial for the treatment of AD. However, the combination of active ingredients and their mechanisms remain unclear. Therefore, we aimed to identify potential active ingredients in F. assafoetida and their mechanisms of action against AD by using network pharmacology. Methods In our study, an integrated network pharmacological approach, that included adsorption, distribution, metabolism and excretion screening, target identification, network construction, topological analysis, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and molecular docking, was used to predict the pharmacological material basis and potential mechanisms through which these ingredients may treat and prevent AD. Results The results indicated that 12 key active ingredients, obtained by topological analysis (including farnesiferol a, conferol, farnesiferol b, ferulic acid, etc.), may be the primary pharmacological components that may ameliorate AD. The 2 key significant pathways identified are the cholinergic synapse signaling pathway (critical targets include ACHE, CHRM1, CHRM2, MAPK1, PIK3CA, PIK3CB, PIK3CD, and PIK3CG) and the AD signaling pathway (critical targets include APP, BACE1, GSK3B, MAPK1, NCSTN, NOS1, PSEN1). These critical targets are closely related to the regulation of three typical pathological features of AD [central nervous system (CNS) cholinergic hypofunction, amyloid-β (Aβ) plaques, and hyperphosphorylated tau proteins]. Finally, 14 critical targets in the 2 key significant pathways were validated by molecular docking analysis. Conclusion F. assafoetida may be effective for alleviating AD symptoms, through multi-component, multi-target, and multi-pathway synergistic effects, associated with the multiple pathogenesis hypotheses of AD. Our study may provide certain clues for the further development and utilization of this natural herbal medicine.

The immunomodulatory activity of a few Lactobacillus exopolysaccharides (EPS) has been reported. However, whether Lactobacillus EPS can promote the differentiation of CD4 T lymphocytes (CD4+T) cells into T-helper 17 cells (Th17 cells) in the Peyer's Patches (PPs) of mice has not been addressed. In this study, we found the molecular weight (Mw) of the purified EPS from L. casei ranged from 2.7 × 106 Da to 1.7 × 107 Da, and the average Mw was approximately 8.4 × 106 Da. In healthy BALB/c mice, EPS elevated the numbers of Th17 cells and levels of Th17-related cytokines. In vitro, EPS induced BMDCs to stimulate the differentiation of CD4+T cells of PPs into Th17 cells and the related cytokine secretions. Results suggest that L. casei EPS can effectively induce and promote the differentiation of CD4+T cells of PPs into Th17 cells in healthy mice and has the potential ability to improve intestinal mucosa immunity.

Aroma style is a complex but critical sensory indicator of flue-cured tobacco. Near infrared spectroscopy was used to investigate the aroma style of flue-cured tobacco. A model screening-sensory validation strategy is herein proposed to overcome obstacles such as the subjectivity of sensory evaluation. Samples with exemplary styles and consistent opinion from a panel were selected as typical samples. Only typical samples were used for modeling. Other samples (atypical samples) were predicted through the proposed model. With references to sensory evaluation, the predictive accuracy reached to 100 and 79.0% for typical and atypical samples, respectively. This method provided a new perspective to evaluate the aroma styles of flue-cured tobacco by a combination of sensory evaluation and chemical analysis.

Intrauterine growth retardation (IUGR) is a serious reproductive problem in humans. The objective of this study was to investigate the effects of daily maternal curcumin supplementation during pregnancy on placental function and fetal growth in a mouse model of IUGR fed the low-protein (LP) diet. Pregnant mice were divided into four groups: (1) normal protein (19% protein) diet (NP); (2) LP (8% protein) diet; (3) LP diet + 100 mg/kg curcumin (LPL); (4) LP diet +400 mg/kg curcumin (LPH). The results showed that the LP group decreased fetal weight, placental weight, placental efficiency, serum progesterone level, placental glutathione peroxidase activity activity, blood sinusoids area, and antioxidant gene expression of placenta. In addition, in comparison with the NP group, LP diet increased serum corticosterone level, placental malondialdehyde content, and apoptotic index. Daily curcumin administration decreased the placental apoptosis, while it increased placental efficiency, placental redox balance, blood sinusoids area, and antioxidant-related protein expression in fetal liver. The antioxidant gene expression of placenta and fetal liver was normalized to the NP level after curcumin administration. In conclusion, daily curcumin supplementation could improve maternal placental function and fetal growth in mice with IUGR.

Cervical cancer, induced by persistent HPV infection, has a high mortality rate. The E3 ubiquitin ligase Cullin 2 (CUL2) is critical for HPV16 E7-mediated degradation of retinoblastoma protein (pRb). Dysregulation of microRNAs (miRNAs) is induced during tumorigenesis; however, the association between miRNA networks and CUL2, specific to cervical cancer, remains unknown. Herein, we determined miRNA profiles in cervical cancer tissues using an Affymetrix miRNA array. We found that miR-154-5p was downregulated during cancer progression using real-time quantitative reverse transcription PCR in 130 biopsy specimens. Bioinformatics analysis and dual-luciferase reporter assays indicated that miR-154-5p directly targets the CUL2 3'UTR. To determine the functional consequences of modulating miR-154-5p and CUL2 levels, HPV16-positive cervical cancer cell line (SiHa) was transfected with miR-154-5p mimic, miR-154-5p inhibitor, or CUL2 siRNA. The proliferation, migration, and invasion of transfected cells were evaluated using CCK8 cell counting kit, wound-healing assay, and Transwell invasion assay. Increased miR-154-5p expression promoted significantly reduced SiHa cell proliferation, migration, and invasion, whereas the miR-154-5p inhibitor had the opposite effect. CUL2 silencing had similar effects to those of the miR-154-5p mimic. Consistent with the inverse correlation between miR-154-5p and CUL2 levels, CUL2 silencing also increased pRb expression. To our knowledge, this is the first study to demonstrate that miR-154-5p regulates pRb expression by targeting CUL2 3'UTR, thereby playing a tumor-suppressive role in HPV16 E7-induced cervical carcinogenesis.

Taste is one of the main chicken soup characteristic quality factors as it affects palatability as well as consumer acceptability. Metabolomics coupled with sensory analysis method were applied to explore the differences of taste-chemical compositions in chicken carcasses and their correlation to the sensory qualities. Results showed that organic acid were the main taste compounds contained in the five kinds of chicken soup samples. The umami taste intensity of chicken breast meat soup was significantly higher than that of the other four parts (p 1).

Acute myocardial infarction (AMI) is a complication of atherosclerosis that takes place in coronary arteries. Cardiac endothelial cells play a significant role in the pathogenesis of AMI. Oxygen-glucose deprivation/reperfusion (OGD/R) is widely used as a model to simulate AMI in vitro. Recently, antidiabetic GLP-1 receptor agonists have been shown to exert pleiotropic effects that modulate cardiovascular complications. In this study, we investigated the vascular effect of lixisenatide. We show that pre-treatment of endothelial cells with lixisenatide protected them from OGD/R-induced cytotoxicity and improved their viability. Pre-treatment with lixisenatide ameliorated OGD/R-induced ROS accumulation and disturbed endothelial tube formation. At the molecular level, lixisenatide mitigated OGD/R-induced reduced eNOS expression and NO production but further promoted the expression of the anti-oxidant regulators Nrf2 and HO-1. Mechanistically, we confirmed that the PI3K/Akt pathway is essential for mediating the effects of lixisenatide, and blockage of PI3K/Akt using the inhibitor LY294002 abolished the ameliorative effect of lixisenatide on ROS production and impaired tube formation. These data indicate that lixisenatide possesses a beneficial effect on the vasculature in a model of ischemia-induced endothelial injury. We conclude that the GLP-1 receptor agonist lixisenatide has pleiotropic properties that can modulate vascular function independent of its anti-glycemic effect.

The amino acid/auxin permease (AAAP) gene family plays a significant role in the long-distance amino acid transport and is involved in plant stress responses and various developmental processes. The functions of the AAAP family have been extensively discussed in multiple organisms, whereas detailed information of this family in strawberry (Fragaria vesca) has not been reported yet. In this study, we identified 45 AAAP genes in the strawberry genome. Phylogenetic analysis indicated that AAAPs from strawberry and Arabidopsis were clustered into eight groups. Expression analysis of the AAAP family showed that AAAP genes were expressed differentially in different developmental stages of flower and fruit, and were significantly induced after Colletotrichum gloeosporioides infection. Our study provides a comprehensive understanding of the strawberry AAAP family and demonstrates their potential roles in disease resistance, providing more reference for further research.

Background Chimeric antigen receptors redirect T cells (CAR-T) to target cancer cells. There are limited data characterizing cardiac toxicity and cardiovascular (CV) events among adults treated with CAR-T. Objectives The purpose of this study was to evaluate the possible cardiac toxicities of CAR-T. Methods The registry included 137 patients who received CAR-T. Covariates included the occurrence and grade of cytokine release syndrome (CRS) and the administration of tocilizumab for CRS. Cardiac toxicity was defined as a decrease in the left ventricular ejection fraction or an increase in serum troponin. Cardiovascular events were a composite of arrhythmias, decompensated heart failure, and CV death. Results The median age was 62 years (interquartile range [IQR]: 54 to 70 years), 67% were male, 88% had lymphoma, and 8% had myeloma. Approximately 50% were treated with commercial CAR-T (Yescarta or Kymriah), and the remainder received noncommercial products. CRS, occurring a median of 5 days (IQR: 2 to 7 days) after CAR-T, occurred in 59%, and 39% were grade ≥2. Tocilizumab was administered to 56 patients (41%) with CRS, at a median of 27 h (IQR: 16 to 48 h) after onset. An elevated troponin occurred in 29 of 53 tested patients (54%), and a decreased left ventricular ejection fraction in 8 of 29 (28%); each occurred only in patients with grade ≥2 CRS. There were 17 CV events (12%, 6 CV deaths, 6 decompensated heart failure, and 5 arrhythmias; median time to event of 21 days), all occurred with grade ≥2 CRS (31% patients with grade ≥2 CRS), and 95% of events occurred after an elevated troponin. The duration between CRS onset and tocilizumab administration was associated with CV events, where the risk increased 1.7-fold with each 12-h delay to tocilizumab. Conclusions Among adults, cardiac injury and CV events are common post–CAR-T. There was a graded relationship among CRS, elevated troponin, and CV events, and a shorter time from CRS onset to tocilizumab was associated with a lower rate of CV events.

This experiment was undertaken to investigate the effects of dietary trans-anethole (TA) at 5 levels (0, 200, 400, 600, and 800 mg/kg of diet) on the growth performance, apparent nutrient digestibility and intestinal barrier function in broilers. Three hundred twenty 1-day-old Arbor Acres broilers were randomly divided into the 5 dietary treatments with 8 replicates each for 42 d. Dietary TA supplementation increased (P < 0.05) average daily feed intake (ADFI), but had no effects (P > 0.05) on average daily gain (ADG), feed/gain (F/G), and body weight (BW) of broilers throughout the entire experimental period. The apparent metabolizable energy (AME) and nitrogen-corrected apparent metabolizable energy (AMEn), the apparent total tract digestibility of dry matter (DM), crude protein (CP), organic matter (OM), and gross energy (GE) showed a quadratic increase (P < 0.05) with the increasing TA concentration in the diet. The apparent ileal digestibility of Lys, Met, Leu, Thr, Ala, Tyr, and Pro were higher (P < 0.05) in birds fed TA diets compared with control group. Dietary supplementation of 400 mg/kg of TA increased (P < 0.05) mRNA levels of jejunal and ileal Na+/glucose co-transporter (SGLT1) on d 21 and d 42, oligopeptide transporter 1 (PepT1) on d 42, and ileal mRNA expressions of occludin (OCLN), claudin-1 (CLDN-1), and mucin 2 (MUC2), villus height (VH), crypt depth (CD), and VH:CD on d 21, as well as jejunal zonula-occludens-1 (ZO-1) and ileal mucin 2 on d 42. Linear or quadratic responses of the jejunal CD and villus VH:CD ratio occurred (P < 0.01) with increasing dietary TA concentration on d 42. The inclusion of 400 mg/kg TA decreased (P < 0.05) cecal Escherichia coli population on d 21 and d 42, but increased (P < 0.05) Bifidobacterium population on d 21 and ileal Bifidobacterium on d 42. In conclusion, 400 mg/kg of TA is the optimum concentration for increasing nutrient utilization and intestinal barrier function of broilers.

A novel Streptomyces strain, designated TRM 75549T, was separated from a sample of sand in Pimo, Taklimakan desert, Xinjiang, North-West China. Phylogenetic analyses of the 16S rRNA gene sequences placed strain TRM75549T within the genus Streptomyces with the highest similarities to Streptomyces flavoviridis NBRC 12772T (98.76%). The whole-genome average nucleotide identity (ANI) value between strain TRM75549T and S. flavoviridis NBRC 12772T is 88.20%. Digital DNA-DNA hybridization (dDDH) value between strain TRM75549T and S. flavoviridis NBRC 12772T is 44.10%. They are well below the recommended 95-96% and 70% cut-off points for designated species respectively. A multi-locus sequence analysis of five house-keeping genes (atpD, gyrB, recA, rpoB and trpB) and phylogenomic analysis also illustrated that strain TRM75549T should be assigned to the genus Streptomyces. Strain TRM75549T contained MK-9 (H6) and MK-9 (H8) as predominant menaquinones. The diagnostic diamino acid of cell walls was identified as LL-diaminopimelic acid and Meso-diaminopimelic. The whole-cell sugar pattern of strain TRM 75549T consisted of mannose and glucose. The major fatty acids (>5%) were iso-C14:0, iso-C15:0, anteiso-C15:0, iso-C16:1H, iso-C16:0. The polar lipids were diphosphatidylglycerol, lysophosphatidylglycerol, phosphatidylethanolamine, phospholipids, phosphatidylglycerol, phosphatidylinositol, phosphatiylinositol mannosides and unidentified phospholipids. Strain TRM75549T could be differentiated from S. flavoviridis NBRC 12772T, based on physiological and biochemical characteristics. Based on the data from this polyphasic study presented above, strain TRM75549T is represent ative of a novel species of the genus Streptomyces, for which the name Streptomyces pimoensis sp. nov. is proposed. The type strain is TRM75549T (=CCTCC AA 2020054T=LMG 32221T ).

Long interspersed element 1 (LINE-1 or L1) is the only active autonomous retrotransposon in the human genome that can serve as an endogenous upstream activator of cytoplasmic nucleic acid sensing pathways to elicit an antiviral immune response. In this study, we investigated the influence of enteroviral infection on L1 mobility. The results showed that infection with different enteroviruses, both EV-D68 and EV-A71, blocked L1 transposition. We screened diverse viral accessory proteins for L1 activity and identified EV-D68 2A, 3A, 3C, and EV-A71 ORF2p proteins as viral L1 inhibitors. EV-D68 2A suppressed L1 mobility by expression suppression of L1 proteins. Viral proteins 3A and 3C restricted ORF2p-mediated L1 reverse transcription in isolated L1 ribonucleoproteins. The newly identified enteroviral protein ORF2p inhibited the expression of L1 ORF1p. Altogether, our findings shed light on the strict modulation of L1 retrotransposons during enterovirus replication.

The integration of HBV DNA into the human genome can disrupt its structure in hepatocellular carcinoma (HCC), but the complexity of HBV genomic integration remains elusive. Here we applied long-read sequencing to precisely elucidate the HBV integration pattern in the human hepatocellular genome. The DNA library was sequenced using the long-read sequencing on GridION and PacBio Sequel II, respectively. The DNA and mRNA were sequenced using next-generation sequencing on Illumina NextSeq. BLAST (Basic Local Alignment Search Tool) and local scripts were used to analyze HBV integration patterns. We established an analytical strategy based on the long-read sequences, and analyzed the complexity of HBV DNA integration into the hepatocellular genome. A total of 88 integrated breakpoints were identified. HBV DNA integration into human genomic DNA was mainly fragmented with different orientations, rarely with a complete genome. The same HBV integration breakpoints were identified among the three platforms. Most breakpoints were observed at P, X, and S genes in the HBV genome, and observed at introns, intergenic sequences, and exons in the human genome. Tumor tissue harbored a much higher integrated number than the adjacent tissue, and the distribution of HBV integrated into human chromosomes was more concentrated. HBV integration shows different patterns between cancer cells and adjacent normal cells. We for the first time obtained the entire HBV integration pattern through long-read sequencing and demonstrated the value of long-read sequencing in detecting the genomic integration structures of viruses in host cells.

Next-generation sequencing and pool sequencing have been widely used in SNP (single-nucleotide polymorphism) detection and population genetics research, however, there are few reports on SNPs related to the growth of Penaeus vannamei. The purpose of this study was to call SNPs from rapid-growing (RG) and slow-growing (SG) individuals’ transcriptomes and use DNA pool sequencing to assess the reliability of SNPs. Two parameters were applied to detect SNPs. One parameter was the p-values generated using Fisher’s exact test, which were used to calculate the significance of allele frequency differences between RG and SG. The other one was the AFI (minor allele frequency imbalance), which was defined to highlight the fold changes in MAF (minor allele frequency) values between RG and SG. There were 216,015 hypothetical SNPs, which were obtained based on the transcriptome data. Finally, 104 high-quality SNPs and 96,819 low-quality SNPs were predicted. Then, 18 high-quality SNPs and 17 low-quality SNPs were selected to assess the reliability of the detection process. Here, 72.22% (13/18) accuracy was achieved for high-quality SNPs, while only 52.94% (9/17) accuracy was achieved for low-quality SNPs. These SNPs enrich the data for population genetics studies of P. vannamei and may play a role in the development of SNP markers for future breeding studies.

The present study used intrauterine growth restriction (IUGR) piglets as an animal model to determine the effect of Bacillus subtilis on intestinal integrity, antioxidant capacity, and microbiota in the jejunum of suckling piglets. In total, 8 normal birth weight (NBW) newborn piglets (1.62 ± 0.10 kg) and 16 newborn IUGR piglets (0.90 ± 0.08 kg) were selected and assigned to three groups. Piglets were orally gavaged with 10-mL sterile saline (NBW and IUGR groups), and IUGR piglets were orally gavaged with 10-mL/d bacterial fluid (B. subtilis diluted in sterile saline, gavage in the dose of 2 × 109 colony-forming units per kg of body weight; IBS group; n = 8). IUGR induced jejunal barrier dysfunction and redox status imbalance of piglets, and changed the abundances of bacteria in the jejunum. Treatment with B. subtilis increased (P < 0.05) the ratio of villus height to crypt depth (VH/CD) in the jejunum, decreased (P < 0.05) the plasma diamine oxidase (DAO) activity, and enhanced (P < 0.05) the gene expressions of zonula occludens-1 (ZO-1), occludin, and claudin-1 in the jejunum of IUGR piglets. Treatment with B. subtilis decreased (P < 0.05) the concentration of protein carbonyl (PC) and increased (P < 0.05) the activities of catalase (CAT) and total superoxide dismutase (T-SOD) in the jejunum of IUGR piglets. Treatment with B. subtilis also increased (P < 0.05) gene expressions of superoxide dismutase 1 (SOD1), CAT, and nuclear factor erythroid 2-related factor (Nrf2), as well as the protein expressions of heme oxygenase-1 (HO-1), SOD1, and Nrf2 in the jejunum of IUGR piglets. Treatment with B. subtilis also improved the abundances and the community structure of bacteria in the jejunum of IUGR piglets. These results suggested that IUGR damaged the jejunal barrier function and antioxidant capacity of suckling piglets, and altered the abundances of bacteria in the jejunum. Treatment with B. subtilis improved the intestinal integrity and antioxidant capacity while also improved the abundances and structure of bacteria in the jejunum of suckling piglets.

Plants are continuously exposed to beneficial and pathogenic microbes, but how plants recognize and respond to friends versus foes remains poorly understood. Here, we compared the molecular response of Arabidopsis thaliana independently challenged with a Fusarium oxysporum endophyte Fo47 versus a pathogen Fo5176. These two Fusarium oxysporum strains share a core genome of about 46 Mb, in addition to unique 1,229 and 5,415 accessory genes. Metatranscriptomic data reveal a shared pattern of expression for most plant genes (∼80%) in responding to both fungal inoculums at all time points from 12 to 96 h post inoculation (HPI). However, the distinct responding genes depict transcriptional plasticity, as the pathogenic interaction activates plant stress responses and suppresses plant growth/development related functions, while the endophytic interaction attenuates host immunity but activates plant nitrogen assimilation. The differences in reprogramming of the plant transcriptome are most obvious in 12 HPI, the earliest time point sampled and are linked to accessory genes in both fungal genomes. Collectively, our results indicate that the A. thaliana and F. oxysporum interaction displays both transcriptome conservation and plasticity in the early stages of infection, providing insights into the fine-tuning of gene regulation underlying plant differential responses to fungal endophytes and pathogens.One-sentence summaryMultiomics analysis reveals the regulatory plasticity of plants in response to beneficial and antagonistic microbes, resulting in distinct phenotypes and rewired transcriptional networks.

Background The Gouqi-wentang formula (GQWTF) is a herbal formula used by Academician Xiao-lin Tong for the clinical treatment of T2DM. GQWTF is beneficial to qi, nourishes Yin, clears heat, and promotes fluid production, but the effective components and their mechanism of action remain unclear. Methods The main components of GQWTF were detected by LC–MS, and the multi-target mechanisms of GQWTF in T2DM were elucidated using network pharmacology analysis, including target prediction, protein–protein interaction network construction and analysis, Gene Ontology (GO) terms, Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway annotation, and other network construction. Finally, the efficacy of the GQWTF was verified using biological experiments. Results First, the “herb-channel tropism” network suggested that GQWTF focuses more on treating diseases by recuperating the liver, which is considered as an important insulin-sensitive organ. Subsequently, a total of 16 active ingredients in GQWTF were detected and screened, and their biological targets were predicted. Then, “compound-target” network was constructed, where enrichment analysis of GQWTF targets reflected its potential pharmacological activities. After T2DM-related target identification, 39 cross targets of GQWTF and T2DM were obtained, and 30 key targets highly responsible for the beneficial effect of GQWTF on T2DM were identified by PPI analysis. GO analysis of these key targets showed that many biological processes of GQWTF in treating T2DM are key in the occurrence and development of T2DM, including components related to inflammatory/immune response, insulin, and metabolism. KEGG analysis revealed the regulation of multiple signalling pathways, such as insulin resistance, PPAR signalling pathway, FoxO signalling pathway, Fc epsilon RI signalling pathway, and pathways that influence diabetes primarily by regulating metabolism as well as other T2DM directly related pathways. Furthermore, a “formula-compound-pathway-symptom” network was constructed to represent a global view of GQWTF in the treatment of T2DM. Conclusions This study explored the mechanism of action of GQWTF in T2DM by multi-component and multi-target multi pathways, which could provide a theoretical basis for the development and clinical application of GQWTF.

The microbial composition of sour porridge at different fermentation times was analyzed through high-throughput sequencing, and a pure culture fermentation process was established to optimize production process and improve the edible quality of the porridge. In natural fermentation, Firmicutes and Proteobacteria were abundant throughout the process. Specifically, Aeromonas, Acinetobacter, and Klebsiella were dominant on fermentation days 1–5 (groups NF-1, NF-3, and NF-5), while Lactobacillus and Acetobacter gradually became the dominant bacteria on fermentation day 7 (group NF-7). Further, we isolated one strain of acid-producing bacteria from sour porridge, identified as Lacticaseibacillus paracasei by 16SrRNA sequencing and annotated as strain SZ02. Pure culture fermentation using this strain significantly increased the relative starch and amylose contents of the porridge, while decreasing the lipid, protein, and ash contents (P < 0.05). These findings suggest that sour porridge produced using strain SZ02 has superior edible qualities and this strategy may be exploited for its industrial production.

Bone marrow mesenchymal stem cells (BMSCs) are a type of adult stem cells that originate from the mesoderm and have important roles in the body because of their self-renewal and multidirectional differentiation potential. Now it has been proved that BMSCs are closely related to the development of osteoporosis (OP). There is growing evidence that lncRNAs are involved in regulating the pyroptosis of BMSCs. And advanced glycation end-products (AGEs) have been recognized as NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome activators. In this study, we aimed to explore the role of lncRNA ORLNC1 (NONMMUT016106.2) on the pyroptosis of BMSCs under CML (Ne-(carboxymethyl) lysine, the most common AGEs) treatment and its specific molecular mechanisms. Our study revealed that CML treatment promoted pyroptosis of BMSCs and upregulated ORLNC1 expression. As a competing endogenous RNA (ceRNA) of miR-200b-3p, the level of ORLNC1 was negatively correlated with miR-200b-3p. Foxo3 was a target of miR-200b-3p and ORLNC1 promoted BMSCs pyroptosis induced by CML through targeting miR-200b-3p/Foxo3 pathway.

Cardiovascular diseases (CVDs) are major causes of mortality and morbidity in the modern society. The rupture of atherosclerotic plaque can induce thrombus formation, which is the main cause of acute cardiovascular events. Recently, many studies have demonstrated that there are some relationships between microbiota and atherosclerosis. In this review, we will focus on the effect of the microbiota and the microbe-derived metabolites, including trimethylamine-N-oxide (TMAO), short-chain fatty acids (SCFAs), and lipopolysaccharide (LPS), on the stability of atherosclerotic plaque. Finally, we will conclude with some therapies based on the microbiota and its metabolites.

The body color of Neocaridina denticulate sinensis is a compelling phenotypic trait, in which a cascade of carotenoid metabolic processes plays an important role. The study was conducted to compare the transcriptome of cephalothoraxes among three pigmentation phenotypes (red, blue, and chocolate) of N. denticulate sinensis. The purpose of this study was to explore the candidate genes associated with different colors of N. denticulate sinensis. Nine cDNA libraries in three groups were constructed from the cephalothoraxes of shrimps. After assembly, 75022 unigenes were obtained in total with an average length of 1026 bp and N50 length of 1876 bp. There were 45977, 25284, 23605, 21913 unigenes annotated in the Nr, Swissprot, KOG, and KEGG databases, respectively. Differential expression analysis revealed that there were 829, 554, and 3194 differentially expressed genes (DEGs) in RD vs BL, RD vs CH, and BL vs CH, respectively. These DEGs may play roles in the absorption, transport, and metabolism of carotenoids. We also emphasized that electron transfer across the inner mitochondrial membrane (IMM) was a key process in pigment metabolism. In addition, a total of 6328 simple sequence repeats (SSRs) were also detected in N. denticulate sinensis. The results laid a solid foundation for further research on the molecular mechanism of integument pigmentation in the crustacean and contributed to developing more attractive aquatic animals.

A Gram-stain-negative, aerobic, rod-shaped bacterium, designated strain TRM85114T, was isolated from Jincaotan in Pamir, PR China. We found it has the ability to degrading 1-naphthylamine. Strain TRM85114T grows at 4-40 °C (optimum, 30 °C), at pH 6.0-9.0 (optimum, pH 6.0-7.0) and with 3%-15% (w/v) NaCl (optimum, 3%-6%). Phylogenetic analysis of 16S rRNA gene sequences revealed that strain TRM85114T is affiliated with the genus Halomonas, sharing high sequence similarity (97.3%) with the type strain of Halomonas korlensis CGMCC 1.6981T. The major fatty acids of strain TRM85114T are C12:0 3-OH, C16:0, C17:0 cyclo, C19:0 cyclo ω8c, summed feature 3 (C16:1 ω7c and/or C16:1 ω6c) and summed feature 8 (C18:1 ω6c and/or C18:1 ω7c). The predominant respiratory quinone is Q-7. The genomic DNA G + C content of strain TRM85114T was determined to be 61.6 mol%. Calculating the average nucleotide identities and the digital DNA-DNA hybridization values between strain TRM85114T and the related type Halomonas strains further revealed that TRM85114T represented a novel species of the genus Halomonas. The name Halomonas jincaotanensis sp. nov. is proposed. The type strain is TRM85114T (CCTCC AB 2021006T =LMG 32311T).

ObjectivesPost-implantation survival and timely vascularization of stem-cell based constructs are critical factors in achieving successful outcomes in tissue regeneration approaches. Hypoxia inducible factor-1α (HIF-1α) is known to mediate adaptive functions to ischemic stress in many different cell types. The current study aimed to explore the role of HIF-1α in post-implantation survival and angio-/vasculogenesis of stem cells from human exfoliated deciduous teeth (SHED).MethodsHIF-1α in SHED was suppressed using siRNA or chemical inhibitor (YC-1) and used in Matrigel plug assay conducted on severe combined immunodeficient mice. The plugs were retrieved on day 3 or 7 post-injection and analyzed for hypoxia status, ki67 expression, DNA fragmentation (TUNEL), cellularity, and vascularization by histology and immunohistochemistry for CD31, HIF-1α, pyruvate dehydrogenase kinase-1 (PDK1), hexokinase 2 (HK2), and glucose transporter 1 (Glut1). Cell viability of HIF-1α silenced SHED under different stress conditions (hypoxia, H2O2, and low glucose) in vitro was measured by CCK-8 assay. CM-H2DCFDA and MitoSOX Red were used to detect cellular and mitochondrial reactive oxygen species (ROS) levels, respectively. PDK1, HK2, and Glut1 expression were measured by western blotting and immunofluorescence. Secretory protein levels of vascular endothelial growth factor (VEGF) and the respective paracrine effects on endothelial cell proliferation and migration were detected by ELISA, CCK-8 assay, and trans-well assay, respectively.ResultsHistological analysis of Matrigel plugs showed significantly reduced cell survival in HIF-1α silenced or chemically inhibited SHED groups, which could be attributed to diminished metabolic adaptations as shown by decreased PDK1, HK2, and Glut1 expression. HIF-1α inhibition in SHED also resulted in significantly low blood vessel formation as observed by a low number of perfused and non-perfused vessels of human or mouse CD31 origin. The viability of HIF-1α silenced SHED was significantly affected under hypoxia, H2O2, and low-glucose conditions in vitro, which was reflected in increased cytoplasmic and mitochondrial ROS levels. Significantly reduced levels of VEGF in HIF-1α silenced SHED resulted in decreased paracrine angiogenic effects as shown by low proliferation and migration of endothelial cells.ConclusionHIF-1α plays an indispensable role in post-implantation survival and angio-/vasculogenic properties of SHED by maintaining ROS homeostasis, inducing metabolic adaptations, and VEGF secretion.

Valproic acid (VPA) is widely used as a eutherapeutic and safe anticonvulsant drug, but the mechanism is not well elucidated. Histone deacetylases (HDACs) were first identified as direct targets of VPA. Many loss-of function mutants in S. pombe have been shown to be VPA sensitive but not sensitive to other HDAC inhibitors, such as sodium butyrate or trichostatin A (TSA). This difference suggests that there are multiple VPA target genes. In the current study, we isolated a VPA-sensitive (vas) mutant, vas4-1, and cloned the VPA target gene vas4+/vrg4+ by performing complementation experiments. The vas4+/vrg4+ gene encodes a putative Golgi GDP-mannose transporter, Vrg4, which is highly homologous with ScVrg4p. Physiological experiments indicated that SpVrg4p is involved in maintaining cell wall integrity (CWI) under high- or low-temperature stress. The results of a coimmunoprecipitation assay suggested that SpVrg4p may be transferred from the ER to the Golgi through SpGot1p loaded COPII vesicles, and both single and double mutations (S263C and A271V) in SpVrg4p compromised this transfer. Our results suggested that CWI in S. pombe is compromised under temperature stress by the VPA-sensitive vas4 mutant.

Even though transcriptional repressors are studied with ever-increasing molecular resolution, the temporal aspects of gene repression remain poorly understood. Here, we address the dynamics of transcriptional repression by Capicua (Cic), which is essential for normal development and is commonly mutated in human cancers and neurodegenerative diseases.(1,2) We report the speed limit for Cic-dependent gene repression based on live imaging and optogenetic perturbations in the early Drosophila embryo, where Cic was originally discovered.(3) Our measurements of Cic concentration and intranuclear mobility, along with real-time monitoring of the activity of Cic target genes, reveal remarkably fast transcriptional repression within minutes of removing an optogenetic de-repressive signal. In parallel, quantitative analyses of transcriptional bursting of Cic target genes support a repression mechanism providing a fast-acting brake on burst generation. This work sets quantitative constraints on potential mechanisms for gene regulation by Cic.

Background and aims Insulin receptor (IR) transduces cell surface signal through phosphoinositide 3-kinase (PI3K)-AKT pathways or translocates to the nucleus and binds to the promoters to regulate genes associated with insulin actions, including de novo lipogenesis (DNL). Chronic activation of IR signaling drives malignant transformation, but the underlying mechanisms remain poorly defined. Down-regulation of fructose-1,6-bisphosphate aldolase (ALDO) B in hepatocellular carcinoma (HCC) is correlated with poor prognosis. We aim to study whether and how ALDOB is involved in IR signaling in HCC. Approach and results Global or liver-specific ALDOB knockout (L-ALDOB-/- ) mice were used in N-diethylnitrosamine (DEN)-induced HCC models, whereas restoration of ALDOB expression was achieved in L-ALDOB-/- mice by adeno-associated virus (AAV). 13 C6 -glucose was employed in metabolic flux analysis to track the de novo fatty acid synthesis from glucose, and nontargeted lipidomics and targeted fatty acid analysis using mass spectrometry were performed. We found that ALDOB physically interacts with IR and attenuates IR signaling through down-regulating PI3K-AKT pathways and suppressing IR nuclear translocation. ALDOB depletion or disruption of IR/ALDOB interaction in ALDOB mutants promotes DNL and tumorigenesis, which is significantly attenuated with ALDOB restoration in L-ALDOB-/- mice. Notably, attenuated IR/ALDOB interaction in ALDOB-R46A mutant exhibits more significant tumorigenesis than releasing ALDOB/AKT interaction in ALDOB-R43A, whereas knockdown IR sufficiently diminishes tumor-promoting effects in both mutants. Furthermore, inhibiting phosphorylated AKT or fatty acid synthase significantly attenuates HCC in L-ALDOB-/- mice. Consistently, ALDOB down-regulation is correlated with up-regulation of IR signaling and DNL in human HCC tumor tissues. Conclusions Our study reports a mechanism by which loss of ALDOB activates IR signaling primarily through releasing IR/ALDOB interaction to promote DNL and HCC, highlighting a potential therapeutic strategy in HCC.

Few studies have focused on the role of dimethylglycine sodium salt (DMG-Na) in protecting the redox status of skeletal muscle, although it is reported to be beneficial in animal husbandry. This study investigated the beneficial effects of DMG-Na on the growth performance, longissimus dorsi muscle (LM) redox status, and mitochondrial function in weaning piglets that were intrauterine growth restricted (IUGR). Ten normal birth weight (NBW) newborn piglets (1.53 ± 0.04 kg) and 20 IUGR newborn piglets (0.76 ± 0.06 kg) from ten sows were obtained. All piglets were weaned at 21 days of age and allocated to three groups with ten replicates per group: NBW-weaned piglets fed a common basal diet (N); IUGR weaned piglets fed a common basal diet (I); IUGR weaned piglets fed a common basal diet supplemented with 0.1% DMG-Na (ID). They were slaughtered at 49 days of age to collect the serum and LM samples. Compared with the N group, the growth performance, LM structure, serum, and, within the LM, mitochondrial redox status, mitochondrial respiratory chain complex activity, energy metabolites, redox status-related, cell adhesion-related, and mitochondrial function-related gene expression, and protein expression deteriorated in group I (P < 0.05). The ID group showed improved growth performance, LM structure, serum, and, within the LM, mitochondrial redox status, mitochondrial respiratory chain complex activity, energy metabolites, redox status-related, cell adhesion-related, and mitochondrial function-related gene expression, and protein expression compared with those in the I group (P < 0.05). The above results indicated that the DMG-Na treatment could improve the LM redox status and mitochondrial function in IUGR weaned piglets via the Nuclear factor erythroid 2-related factor 2 (Nrf2)/ Sirtuin 1 (SIRT1)/ Peroxisome proliferator-activated receptorγcoactivator-1α (PGC1α) network, thus improving their growth performance.