Pseudomonas protegens volatile organic compounds inhibited brown rot of postharvest peach fruit by repressing the pathogenesis-related genes in Monilinia fructicola.

Brown rot, caused by Monilinia fructicola, is considered one of the devasting diseases of pre-harvest and post-harvest peach fruits, restricting the yield and quality of peach fruits and causing great economic losses to the peach industry every year. Presently, the management of the disease relies heavily on chemical control. In the study, we demonstrated that the volatile organic compounds (VOCs) of endophyte bacterial Pseudomonas protegens QNF1 inhibited the mycelial growth of M. fructicola by 95.35% compared to the control, thereby reducing the brown rot on postharvest fruits by 98.76%. Additionally, QNF1 VOCs severely damaged the mycelia of M. fructicola. RNA-seq analysis revealed that QNF1 VOCs significantly repressed the expressions of most of the genes related to pathogenesis (GO:0009405) and integral component of plasma membrane (GO:0005887), and further analysis revealed that QNF1 VOCs significantly altered the expressions of the genes involved in various metabolism pathways including Amino acid metabolism, Carbohydrate metabolism, and Lipid metabolism. The findings of the study indicated that QNF1 VOCs displayed substantial control efficacy by disrupting the mycelial morphology of M. fructicola, weakening its pathogenesis, and causing its metabolic disorders. The study provided a potential way and theoretical support for the management of the brown rot of peach fruits.

Bio-availability of potential trace elements in urban dust, soil, and plants in arid northwest China.

Potential trace elements pollution in cities poses a threat to the environment and human health. Bio-availability affects toxicity levels of potential trace elementss on organisms. This study focused on exploring the relationship between soil, plant, and atmospheric dust pollution in Urumqi, a typical city in western China. It aims to help reduce pollution and protect residents' health. The following conclusions were drawn: 1) potential trace elementss like Cr, Pb, As, and Ni are more prevalent in atmospheric dust and soil than in plants. Chromium was in the first group, Cadmium and Mercury were in the second, and Plumb, Arsenic, and Nickel were in the third. Atmospheric dust and soil exhibit a significantly higher heavy metal content than plants. For example, The atmospheric dust summary Chromium content was up to 88 mg/kg. 2) Soil, atmospheric dust, and plants have the highest amount of residual form. Residual form had the highest percentage average of 53.3%, whereas Organic matter bound form had the lowest percentage of just 7.7%. The plants contained less residual heavy metal than the soil and atmospheric dust. 3) The correlation coefficient between the carbonated form content of Cd of soil and atmospheric dust is 0.95, which is closely related. Other potential trace elements show similar correlations in their bio-available contents in soil, plants, and atmospheric dust.This study suggests that in urban area, the focus should be on converting potential trace elements into residual form instead of increasing plants' absorption of potential trace elements.

The current research in China primarily examines heavy metal pollution in the atmosphere, soil, and plants individually. Although there is significant international research on heavy metal bio-availability in the environment, few studies have focused on the presence of heavy metals in soil, vegetation, and atmospheric dust.Therefore, this study focused on Urumqi, the capital of Xinjiang, a typical oasis city in the arid region. To understand the bio-availability and morphological characteristics of heavy metals (Cd, Pb, Hg, Cr, As, Ni) in the soil-plant-atmosphere of its urban expressway.This study aims to establish a theoretical basis for understanding the pollution hazards caused by heavy metals in oasis cities. It will have practical significance in maintaining urban ecology, promoting sustainable development, and safeguarding citizens' health.

Environmental Hormone Effects and Bioaccumulation of Propiconazole and Difenoconazole in Procypris merus.

Studying the bioaccumulation behavior and toxicity of triazole fungicides is a crucial part of comprehensively evaluating the environmental fate and aquatic toxicity.The current research aimed to reveal the toxic effects of propiconazole and difenoconazole on fish through acute toxicity test, bioaccumulation test and oxidase system activity determination. Here, the propiconazole and difenoconazole concentrations were 11.3 mg/L and 31.2 mg/L for LC50-96 h, both having low toxicity. LC-MS/MS was used to determine the propiconazole and difenoconazole concentrations in five organs (muscle, gill, liver, intestine, and kidney) of Procypris meru. The findings indicate that the bioconcentration coefficients of propiconazole and difenoconazole in grass flower carp were 0.66-27.08 and 2.43-22.72, which belonged to medium enrichment pesticides. The bioconcentration coefficients decreased with the increase of exposure concentration. The two fungicides could induce oxidative stress in fish liver, and the activities of three antioxidant enzymes were inhibited in varying degrees (p < 0.05). The results showed that the content of T3 increased, and T4 decreased when exposed to one-tenth LC50 for 7 days. This study shows that triazole pesticides have bioaccumulation risks on aquatic organisms and clear environmental hormonal effects.

Total Synthesis of (-)-Indoxamycins†A and B.

The concise total syntheses of (-)-indoxamycins A and B is reported. The chemistry features a seven-step preparation of a highly congested [5.5.6] tricyclic advanced common intermediate from a readily available R-carvone derivative. Key steps involve a Pauson-Khand reaction for the rapid construction of a basic scaffold bearing a quaternary carbon, a copper-catalyzed Michael addition for the introduction of another adjacent all-carbon quaternary stereocenter, and a tandem retro-oxa-Michael addition/1,2-addition/oxa-Michael addition for the installation of a trisubstituted olefin side chain. This synthetic strategy allows for easy access to both enantiomers of this family of natural products and their analogues from cost-effective starting material through straightforward chemical transformations.

Molecular binding behaviors and thermodynamics of ferrocenyl dimethylaminium derivatives by anionic pillar[5]arene.

A novel anionic water-soluble pillar[5]arene (4C-WP5A) was synthesized via a convenient synthetic strategy of the direct cyclization of a functionalized hydroquinone monomer. The alkyl chain dependent affinities of ferrocenyl aminiums (FCn(+), n: carbon number) with 4C-WP5A are driven by hydrophobic interactions and desolvations with assisted C-H···π interactions and electrostatic interactions.

LY294002 enhances inhibitory effect of gemcitabine on proliferation of human pancreatic carcinoma PANC-1 cells.

Phosphatidylinositide 3-kinase (PI3K)/protein kinase B (PKB, Akt) pathway plays a major role in proliferation and survival of many types of cells. The inhibitory effect of LY294002, widely applied as an inhibitor of PI3K, in combination with gemcitabine on proliferation of PANC-1 cells was investigated. The expression of PI3K, phosphorylated Akt (p-Akt) and multidrug-resistance like protein (MRP) in normal pancreas tissues, chronic pancreatitis tissues and pancreatic carcinoma tissues was detected. The effects of LY294002 combined with gemcitabine on proliferation of PANC-1 cells and protein levels of p-Akt and MRP were detected. The results showed that the positive expression rate of PI3K, p-Akt and MRP in pancreatic carcinoma tissues was significantly higher than that in normal pancreas tissues and chronic pancreatitis tissues (P<0.01 and P<0.05 respectively). LY294002 could effectively enhance the inhibitory effect of gemcitabine on proliferation of PANC-1 cells. Furthermore, Western blotting revealed that LY294002 combined with gemcitabine reduced the protein levels of p-Akt and MRP, which contributed to the inhibition of proliferation. It is concluded that LY294002 in combination with gemcitabine may represent an alternative therapy for pancreatic carcinoma.

Chick chorioallantoic membrane model to investigate role of migrasome in angiogenensis.

The development of the vascular system is essential for embryonic development, including processes such as angiogenesis. Angiogenesis plays a critical role in many normal physiological and pathological processes. It is driven by a set of angiogenic proteins, including angiogenic growth factors, chemokines, and extracellular matrix proteins. Among various animal model systems, the chorioallantoic membrane (CAM), a specialized and highly vascularized tissue of the avian embryo, has proven to be a valuable tool for analyzing the angiogenic potential of candidate cells or factors. In this protocol, we provide detailed procedures for establishing the CAM model to evaluate the function and mechanism of migrasomes in embryonic angiogenesis. This includes the CAM nylon mesh assay and CAM ex vivo sprouting assay to assess CAM angiogenesis, as well as the observation, purification, and delivery of migrasomes. Additionally, we describe the generation of T4-KO-mCherry-KI embryos using the CRISPR system within the CAM tissue to investigate the role of migrasomes in angiogenesis.

Nonsynonymous C1653T Mutation of Hepatitis B Virus X Gene Enhances Malignancy of Hepatocellular Carcinoma Cells.

Purpose: Functional analysis was performed to elucidate the mechanism by which hepatocellular carcinoma (HCC) outcome-associated mutation in the hepatitis B virus X (HBx) gene modifies the HCC process. Methods: Proliferation, invasion, migration, and apoptosis assays were performed, and changes in fibrosis, intracellular reactive oxygen species (ROS), and cytokine levels were measured. The differences between variables were evaluated by Student's t-test. Results: The influence of two previously identified nonsynonymous mutation, C1653T and T1753C, on HCC cells was assessed. With regard to HBX-induced promotion of proliferation (p < 0.01), invasion (p < 0.01) and migration (p < 0.01), the C1653T mutation displayed a significant additive effect in these assays (P < 0.05). The subsequent apoptosis assay indicated that HBX could inhibit apoptosis (P < 0.01), whereas the C1653T mutation markedly amplified this effect in HCC cells (P < 0.01). Furthermore, the tumor growth-promoting effect of HBX was confirmed in a mouse xenograft model of HCC (P < 0.05), and the C1653T mutation was observed to amplify this effect (P < 0.05). To further investigate the mechanism by which the C1653T mutation enhances malignancy in HCC cells, fibrosis, intracellular ROS, and cytokine levels were measured. The C1653T mutant increased fibrosis and intracellular ROS level, and altered monocyte chemotactic protein-1 and interleukin-18 expression in HepG2 cells. Drug sensitivity test revealed that the C1653T mutation is sensitive to apatinib treatment and that overexpression of vascular endothelial growth factor might be involved in this process. Conclusion: Our data indicate that the C1653T mutation of HBx promotes HCC malignancy by altering the levels of fibrosis, ROS, and some cytokines. This mutation could serve as a potential biomarker for screening HCC patients to determine apatinib treatment efficacy.

Analytical method for sequential determination of persistent herbicides and their metabolites in fish tissues by UPLC-MS/MS.

A novel and accurate liquid chromatography-tandem mass spectrometry method was developed to sequentially determine three persistent herbicides (atrazine (ATZ), acetochlor (ACE), and metolachlor (MET)) and seven characteristic metabolites (desethylatrazine (DEA), deisopropylatrazine (DIA), diaminochlorotriazine (DACT), MET-oxanilic acid (MET-OA), MET-ethanesulfonic acid (MET-ESA), ACE-ESA, and ACE-OA) in fresh fish tissues from six fish species. A modified QuEChERS method was conducted to extract the target compounds from fish tissues. Matrix-matched calibrations of the target analytes were carried out at spiking levels of 1, 10, 100, and 1000 ng g-1. The method was validated in accordance with Codex guidelines (CAC/GL 71-2009). Recoveries for the target analytes were 67-120% with relative standard deviations below 20%, and the matrix effects ranged from -58.7% to 59.3%. The limits of detection and quantitation were 0.01-1.90 and 0.02-6.35 ng g-1, respectively. Moreover, the method was successfully applied to analyze the concentrations of the target chemicals in fresh tissue samples of six fish species (n = 67) collected from four markets in Nanning City, Guangxi Province, China. The concentrations in all samples were 1.1-140.5 ng g-1. Interestingly, this study was the first to measure DEA and DIA in fish liver, and their highest concentrations were 10.7 and 14.2 ng g-1, respectively. This method provides a basis for studying the pathways of biotransformation, bioaccumulation, detoxification, and exposure patterns of ACE, ATZ, MET, and their metabolites in aquatic environments.

Monocytes deposit migrasomes to promote embryonic angiogenesis.

Pro-angiogenic factors are key regulators of angiogenesis. Here we report that highly migratory cells patrol the area of capillary formation in chick embryo chorioallantoic membrane. These cells deposit migrasomes on their migration tracks, creating migrasome-enriched areas. Single-cell sequencing identified these cells as monocytes. Depletion of monocytes impairs capillary formation. Quantitative mass spectrometry analysis reveals that monocyte migrasomes are enriched with pro-angiogenic factors. Purified migrasomes promote capillary formation and monocyte recruitment in vivo, and endothelial cell tube formation and monocyte chemotaxis in vitro. Knockdown or knockout of TSPAN4 reduces migrasome formation and impairs capillary formation and monocyte recruitment. Mechanistically, monocytes promote angiogenesis via VEGFA and CXCL12 in migrasomes. In summary, monocytes deposit migrasomes enriched in pro-angiogenic factors to promote angiogenesis.

FHA domain of AGGF1 is essential for its nucleocytoplasmic transport and angiogenesis.

Angiogenic factor with G-patch and FHA domains 1 (AGGF1) exhibits a dynamic distribution from the nucleus to the cytoplasm in endothelial cells during angiogenesis, but the biological significance and underlying mechanism of this nucleocytoplasmic transport remains unknown. Here, we demonstrate that the dynamic distribution is essential for AGGF1 to execute its angiogenic function. To search the structural bases for this nucleocytoplasmic transport, we characterized three potential nuclear localization regions, one potential nuclear export region, forkhead-associated (FHA), and G-patch domains to determine their effects on nucleocytoplasmic transport and angiogenesis, and we show that AGGF1 remains intact during the dynamic subcellular distribution and the region from 260 to 288 amino acids acts as a signal for its nuclear localization. The distribution of AGGF1 in cytoplasm needs both FHA domain and 14-3-3α/ß. Binding of AGGF1 via FHA domain to 14-3-3α/ß is required to complete the transport. Thus, we for the first time established structural bases for the nucleocytoplasmic transport of AGGF1 and revealed that the FHA domain of AGGF1 is essential for its nucleocytoplasmic transport and angiogenesis.

Down-regulated RGS5 by genetic variants impairs endothelial cell function and contributes to coronary artery disease.

AIMS: Genetic contribution to coronary artery disease (CAD) remains largely unillustrated. Although transcriptomic profiles have identified dozens of genes that are differentially expressed in normal and atherosclerotic vessels, whether those genes are genetically associated with CAD remains to be determined. Here, we combined genetic association studies, transcriptome profiles and in vitro and in vivo functional experiments to identify novel susceptibility genes for CAD. METHODS AND RESULTS: Through an integrative analysis of transcriptome profiles with genome-wide association studies for CAD, we obtained 18 candidate genes and selected one representative single nucleotide polymorphism (SNP) for each gene for multi-centred validations. We identified an intragenic SNP, rs1056515 in RGS5 gene (odds ratio = 1.17, 95% confidence interval =1.10-1.24, P = 3.72 × 10-8) associated with CAD at genome-wide significance. Rare genetic variants in linkage disequilibrium with rs1056515 were identified in CAD patients leading to a decreased expression of RGS5. The decreased expression was also observed in atherosclerotic vessels and endothelial cells treated by various cardiovascular risk factors. Through siRNA knockdown and adenoviral overexpression, we further showed that RGS5 regulated endothelial inflammation, vascular remodelling, as well as canonical NF-κB signalling activation. Moreover, CXCL12, a specific downstream target of the non-canonical NF-κB pathway, was strongly affected by RGS5. However, the p100 processing, a well-documented marker for non-canonical NF-κB pathway activation, was not altered, suggesting an existence of a novel mechanism by which RGS5 regulates CXCL12. CONCLUSIONS: We identified RGS5 as a novel susceptibility gene for CAD and showed that the decreased expression of RGS5 impaired endothelial cell function and functionally contributed to atherosclerosis through a variety of molecular mechanisms. How RGS5 regulates the expression of CXCL12 needs further studies.

Mild Friedel-Crafts Reactions Enable a Robust Synthesis of Roseophilin.

An 11-step total synthesis of either enantiomer of roseophilin has been developed. The chemistry features effective production of a challenging carbocation on a macrocyclic segment 25 and a highly efficient intermolecular Friedel-Crafts alkylation reaction to integrate a complex furan-pyrrole unit 5 regioselectively with this carbocation under very mild reaction conditions.

Hydrolysis and photolysis of bentazone in aqueous abiotic solutions and identification of its degradation products using quadrupole time-of-flight mass spectrometry.

Hydrolysis and photolysis of bentazone in abiotic aqueous solutions were examined under laboratory conditions. Hydrolysis was studied in different buffer solutions (pH 4.0 ± 0.1, 7.0 ± 0.1, and 9.0 ± 0.1), at different temperatures (15 °C ± 2 °C, 25 °C ± 2 °C, 35 °C ± 2 °C, and 45 °C ± 2 °C), and at different Fe3+ concentrations (1, 5, and 10 mg/L). Photolysis was assessed in different buffer solutions and at different solvent (methanol and ethyl acetate) concentrations (10%, 20%, and 30%) or Fe3+ (1, 5, and 10 mg/L) concentrations and under mercury or xenon light irradiation. Hydrolysis half-lives ranged 46-99 days at three different conditions. Photolysis half-lives ranged 2.3-7.5 h in three different conditions under mercury and xenon irradiation. Hydrolysis and photolysis of bentazone were accelerated by both alkaline conditions and elevated temperatures, and solvents and Fe3+ strongly enhanced bentazone degradation. Photodecomposition was much faster under a mercury lamp than under a xenon lamp. N-methyl bentazone and 6-OH bentazone/8-OH bentazone were identified as degradation products using UPLC-Q-TOF-MS. The data generated from this study could be useful for risk assessment of pesticides in the environment.

Simultaneous determination of neonicotinoid insecticides and insect growth regulators residues in honey using LC-MS/MS with anion exchanger-disposable pipette extraction.

In this study, we developed an anion exchanger-disposable pipette extraction (DPX) method to detect the residual concentrations of eight neonicotinoid insecticides (dinotefuran, acetamiprid, clothianidin, thiacloprid, imidachloprid, imidaclothiz, nitenpyram, and thiamethoxam) and eight insect growth regulators (IGRs; triflumuron, cyromazine, buprofezin, methoxyfenozide, tebufenozide, chromafenozide, fenoxycarb, and RH 5849) in Chinese honey samples collected from different floral sources and different geographical regions using liquid chromatography tandem mass spectrometry (LC-MS/MS). QAE Sephadex A-25 was used as the anion exchanger in the DPX column for the purification and cleanup of honey samples. Analytes were eluted with a mixture of acetonitrile and 0.1 M HCl, and the elution was subjected to LC analysis. This method was thoroughly validated for its reproducibility, linearity, trueness, and recovery. Satisfactory recovery of pesticides was obtained ranging from 72% to 111% with intraday RSDs (n = 5) of 1%-10%. High linearity (R2 ≥ 0.9987) was observed for all 16 pesticides. Limits of detection and quantification for all 16 compounds ranged from 0.3 to 3 µg/kg and from 1 to 10 µg/kg, respectively. Pesticide residues (9-113 µg/kg) were found in Chinese honey samples. The anion exchanger-DPX method was effective for removing sugars and retaining target analytes. Moreover, this method was highly reliable and sensitive for detecting neonicotinoids and IGRs in different floral sources of honey and will be applicable to matrixes with high sugar content.

Size Switchable Supramolecular Nanoparticle Based on Azobenzene Derivative within Anionic Pillar[5]arene.

A photo/thermal-switchable supramolecular nanoparticles assembly has been constructed based on an inclusion complex between anionic pillar[5]arene 2C-WP5A and azobenzene derivative Azo-py-OMe (G). The novel anionic pillar[5]arene-based host-guest inclusion complexation was investigated by the 1H NMR titration, 2D ROESY and isothermal titration microcalorimetry (ITC) showing high association constant (Ka) of (2.60 ± 0.06) × 104 M-1 with 1:1 binding stoichiometry. Furthermore, the supramolecular nanoparticles assembly can be conveniently obtained from G and a small amount of 2C-WP5A in aqueous solution, which was so-called "host induced aggregating (HIA)". The size and morphology of the supramolecular nanoparticles assembly were characterized by TEM and DLS. As a result of the photo/thermal-isomerization of G included in the cavity of 2C-WP5A, the size of these nanoparticles could reversibly change from ~800 nm to ~250 nm, which could switch the solution of this assembly from turbid to clear.

Mutational and functional analysis of the BVES gene coding region in Chinese patients with non-syndromic tetralogy of Fallot.

Tetralogy of Fallot (TOF) is a common congenital heart defect (CHD). However, the genetic causes are largely unknown. Blood vessel epicardial substance (BVES) is postulated to play a role in embryonic development, and we previously found that the expression of BVES is upregulation in patients with congenital septal defect and that BVES participates in cardiocyte differentiation. We hypothesized that BVES is a candidate gene of TOF. In the present study, the entire coding sequence and splice junctions of BVES were sequenced in 114 unrelated patients with TOF and 400 unrelated healthy individuals used as controls. The functional effects of the exon mutant BVES were characterized in contrast to its wild-type counterpart using a luciferase reporter assay system. Four novel BVES mutations (c.166T>C, c.909C>T, c.540-80C>T, c.958+30A>G) were identified in patients with TOF but not in the 400 controls. Functional analysis indicated that the c.166T>C mutation of BVES was associated with an increased transcriptional activity. This finding suggests that BVES as a novel TOF gene may provide further insight into the molecular mechanisms involved in TOF.