Content analysis and drug safety evaluation of four furanocoumarins in six pomelos produced in China

The content of 4 6',7'-dihydroxybergamottin (DHB), bergamottin, isoimperatorin and epoxybergamottin of six pomelos produced in China were detected by High-performance liquid chromatography-diode array detection and their safety of related medicines was evaluated by inhibition of medium concentration (IC50) of cytochrome oxidases CYP450-like. The results showed that the total content of the four furanocoumarins in these pomelo juices from high to low in order was Guanximi pomelo > Liangping pomelo > Pinghemi pomelo > grapefruit > Huyou > Shatian pomelo. The concentration of isoimperatorin in grapefruit, DHB, bergamottinand and isoimperatorin in Liangping, bergamottin and epoxybergamottin in Pinghemi and all the four furanocoumarins in Guanximi were exceeded the corresponding IC50; although Huyou and Shatian contained some furanocoumarins, they did not exceed IC50. Therefore, when taking drugs metabolised by CYP450-like enzymes, Guanximi, Liangping, Pinghemi, and grapefruit should be avoided to consume, but it is relatively safe to eat Huyou and Shatian.</p

Table_2_Comparative Extracellular Proteomics of Aeromonas hydrophila Reveals Iron-Regulated Secreted Proteins as Potential Vaccine Candidates.DOC

In our previous study, several iron-related outer membrane proteins in Aeromonas hydrophila, a serious pathogen of farmed fish, conferred high immunoprotectivity to fish, and were proposed as potential vaccine candidates. However, the protective efficacy of these extracellular proteins against A. hydrophila remains largely unknown. Here, we identified secreted proteins that were differentially expressed in A. hydrophila LP-2 in response to iron starvation using an iTRAQ-based quantitative proteomics method. We identified 341 proteins, of which 9 were upregulated in response to iron starvation and 24 were downregulated. Many of the differently expressed proteins were associated with protease activity. We confirmed our proteomics results with Western blotting and qPCR. We constructed three mutants by knocking out three genes encoding differentially expressed proteins (Δorf01830, Δorf01609, and Δorf03641). The physiological characteristics of these mutants were investigated. In all these mutant strains, protease activity decreased, and Δorf01609, and Δorf01830 were less virulent in zebrafish. This indicated that the proteins encoded by these genes may play important roles in bacterial infection. We next evaluated the immune response provoked by the six iron-related recombinant proteins (ORF01609, ORF01830, ORF01839, ORF02943, ORF03355, and ORF03641) in zebrafish as well as the immunization efficacy of these proteins. Immunization with these proteins significantly increased the zebrafish immune response. In addition, the relative percent survival (RPS) of the immunized zebrafish was 50–80% when challenged with three virulent A. hydrophila strains, respectively. Thus, these extracellular secreted proteins might be effective vaccine candidates against A. hydrophila infection in fish.</p

Table_3_Comparative Extracellular Proteomics of Aeromonas hydrophila Reveals Iron-Regulated Secreted Proteins as Potential Vaccine Candidates.DOC

In our previous study, several iron-related outer membrane proteins in Aeromonas hydrophila, a serious pathogen of farmed fish, conferred high immunoprotectivity to fish, and were proposed as potential vaccine candidates. However, the protective efficacy of these extracellular proteins against A. hydrophila remains largely unknown. Here, we identified secreted proteins that were differentially expressed in A. hydrophila LP-2 in response to iron starvation using an iTRAQ-based quantitative proteomics method. We identified 341 proteins, of which 9 were upregulated in response to iron starvation and 24 were downregulated. Many of the differently expressed proteins were associated with protease activity. We confirmed our proteomics results with Western blotting and qPCR. We constructed three mutants by knocking out three genes encoding differentially expressed proteins (Δorf01830, Δorf01609, and Δorf03641). The physiological characteristics of these mutants were investigated. In all these mutant strains, protease activity decreased, and Δorf01609, and Δorf01830 were less virulent in zebrafish. This indicated that the proteins encoded by these genes may play important roles in bacterial infection. We next evaluated the immune response provoked by the six iron-related recombinant proteins (ORF01609, ORF01830, ORF01839, ORF02943, ORF03355, and ORF03641) in zebrafish as well as the immunization efficacy of these proteins. Immunization with these proteins significantly increased the zebrafish immune response. In addition, the relative percent survival (RPS) of the immunized zebrafish was 50–80% when challenged with three virulent A. hydrophila strains, respectively. Thus, these extracellular secreted proteins might be effective vaccine candidates against A. hydrophila infection in fish.</p

Table_1_Comparative Extracellular Proteomics of Aeromonas hydrophila Reveals Iron-Regulated Secreted Proteins as Potential Vaccine Candidates.DOCX

In our previous study, several iron-related outer membrane proteins in Aeromonas hydrophila, a serious pathogen of farmed fish, conferred high immunoprotectivity to fish, and were proposed as potential vaccine candidates. However, the protective efficacy of these extracellular proteins against A. hydrophila remains largely unknown. Here, we identified secreted proteins that were differentially expressed in A. hydrophila LP-2 in response to iron starvation using an iTRAQ-based quantitative proteomics method. We identified 341 proteins, of which 9 were upregulated in response to iron starvation and 24 were downregulated. Many of the differently expressed proteins were associated with protease activity. We confirmed our proteomics results with Western blotting and qPCR. We constructed three mutants by knocking out three genes encoding differentially expressed proteins (Δorf01830, Δorf01609, and Δorf03641). The physiological characteristics of these mutants were investigated. In all these mutant strains, protease activity decreased, and Δorf01609, and Δorf01830 were less virulent in zebrafish. This indicated that the proteins encoded by these genes may play important roles in bacterial infection. We next evaluated the immune response provoked by the six iron-related recombinant proteins (ORF01609, ORF01830, ORF01839, ORF02943, ORF03355, and ORF03641) in zebrafish as well as the immunization efficacy of these proteins. Immunization with these proteins significantly increased the zebrafish immune response. In addition, the relative percent survival (RPS) of the immunized zebrafish was 50–80% when challenged with three virulent A. hydrophila strains, respectively. Thus, these extracellular secreted proteins might be effective vaccine candidates against A. hydrophila infection in fish.</p

Data_Sheet_1_Comparative Extracellular Proteomics of Aeromonas hydrophila Reveals Iron-Regulated Secreted Proteins as Potential Vaccine Candidates.doc

In our previous study, several iron-related outer membrane proteins in Aeromonas hydrophila, a serious pathogen of farmed fish, conferred high immunoprotectivity to fish, and were proposed as potential vaccine candidates. However, the protective efficacy of these extracellular proteins against A. hydrophila remains largely unknown. Here, we identified secreted proteins that were differentially expressed in A. hydrophila LP-2 in response to iron starvation using an iTRAQ-based quantitative proteomics method. We identified 341 proteins, of which 9 were upregulated in response to iron starvation and 24 were downregulated. Many of the differently expressed proteins were associated with protease activity. We confirmed our proteomics results with Western blotting and qPCR. We constructed three mutants by knocking out three genes encoding differentially expressed proteins (Δorf01830, Δorf01609, and Δorf03641). The physiological characteristics of these mutants were investigated. In all these mutant strains, protease activity decreased, and Δorf01609, and Δorf01830 were less virulent in zebrafish. This indicated that the proteins encoded by these genes may play important roles in bacterial infection. We next evaluated the immune response provoked by the six iron-related recombinant proteins (ORF01609, ORF01830, ORF01839, ORF02943, ORF03355, and ORF03641) in zebrafish as well as the immunization efficacy of these proteins. Immunization with these proteins significantly increased the zebrafish immune response. In addition, the relative percent survival (RPS) of the immunized zebrafish was 50–80% when challenged with three virulent A. hydrophila strains, respectively. Thus, these extracellular secreted proteins might be effective vaccine candidates against A. hydrophila infection in fish.</p

Table_4_Comparative Extracellular Proteomics of Aeromonas hydrophila Reveals Iron-Regulated Secreted Proteins as Potential Vaccine Candidates.XLSX

In our previous study, several iron-related outer membrane proteins in Aeromonas hydrophila, a serious pathogen of farmed fish, conferred high immunoprotectivity to fish, and were proposed as potential vaccine candidates. However, the protective efficacy of these extracellular proteins against A. hydrophila remains largely unknown. Here, we identified secreted proteins that were differentially expressed in A. hydrophila LP-2 in response to iron starvation using an iTRAQ-based quantitative proteomics method. We identified 341 proteins, of which 9 were upregulated in response to iron starvation and 24 were downregulated. Many of the differently expressed proteins were associated with protease activity. We confirmed our proteomics results with Western blotting and qPCR. We constructed three mutants by knocking out three genes encoding differentially expressed proteins (Δorf01830, Δorf01609, and Δorf03641). The physiological characteristics of these mutants were investigated. In all these mutant strains, protease activity decreased, and Δorf01609, and Δorf01830 were less virulent in zebrafish. This indicated that the proteins encoded by these genes may play important roles in bacterial infection. We next evaluated the immune response provoked by the six iron-related recombinant proteins (ORF01609, ORF01830, ORF01839, ORF02943, ORF03355, and ORF03641) in zebrafish as well as the immunization efficacy of these proteins. Immunization with these proteins significantly increased the zebrafish immune response. In addition, the relative percent survival (RPS) of the immunized zebrafish was 50–80% when challenged with three virulent A. hydrophila strains, respectively. Thus, these extracellular secreted proteins might be effective vaccine candidates against A. hydrophila infection in fish.</p

Integrated Computational and Experimental Framework for Inverse Screening of Candidate Antibacterial Nanomedicine

Nanomedicine is promising for disease prevention and treatment, but there are still many challenges that hinder its rapid development. A major challenge is to efficiently seek candidates with the desired therapeutic functions from tremendously available materials. Here, we report an integrated computational and experimental framework to seek alloy nanoparticles from the Materials Project library for antibacterial applications, aiming to learn the inverse screening concept from traditional medicine for nanomedicine. Because strong peroxidase-like catalytic activity and weak toxicity to normal cells are the desired material properties for antibacterial usage, computational screening implementing theoretical prediction models of catalytic activity and cytotoxicity is first conducted to select the candidates. Then, experimental screening based on scanning probe block copolymer lithography is used to verify and refine the computational screening results. Finally, the best candidate AuCu3 is synthesized in solution and its antibacterial performance over other nanoparticles against S. aureus and E. coli. is experimentally confirmed. The results show the power of inverse screening in accelerating the research and development of antibacterial nanomedicine, which may inspire similar strategies for other nanomedicines in the future

Table1_Three-stage hydrocarbon accumulations in the Middle Permian in the Central Sichuan Basin.pdf

The Middle Permain Maokou Formation (P2m) is a new region of natural gas exploration in the Sichuan Basin, is characterized by bioclastic limestone with localized dolomitization, and karst fractured-vuggy reservoirs. Currently, on the gas source, hydrocarbon accumulation process and control factors in the Sichuan Basin during the Permian are lacking. To bridge this gap, herein, we identified the filling sequence minerals inside the pores/vugs, along with the oil charge of the Maokou Formation using drill cores, thin sections, oil inclusion analysis, and U-Pb dating of calcite cements. The results showed that the reservoir space of the Maokou Formation was predominated by the residual dissolved pores/vugs, fractures, and dissolved fractures. The pores/vugs underwent four stages of mineral filling by very fine-fine (-crystalline, CC1) calcite → fine-medium calcite (CC2: from 256.4 ± 1.7 to 244.1 ± 6.3 Ma) → fibrous calcite (FC; ∼183.9 ± 8.2 Ma) → coarse-macro calcite (CC3; ∼171.5 ± 5.3 Ma). Combined with the homogenization temperature and salty of fluid inclusion, we considered that three stages of oil charge were present in the Maokou Formation reservoirs. The first stage involved the formation of paleo-oil reservoirs during the Late Permian to Early Triassic, corresponding to the high-maturity aqueous inclusions in CC2, with a homogenization temperature of 106.7°C–137.8°C. At that time, the oil generation from the Lower Cambrian Qiongzhusi Formation rocks peaked, and the generated hydrocarbons migrated upward into the Maokou Formation through the strike-slip faults in the basin center. The second stage involved the formation of paleo-oil reservoirs during the Early Jurassic. The Permian source rocks reached the oil generation window with hydrocarbon expulsion, which was consistent with the oil inclusions in FC. The third stage involved the formation of paleo-gas reservoirs during the Middle Jurassic to Early Cretaceous, corresponding to the high-density methane inclusions and bitumen inclusions occurring in CC3, with the homogenization temperature peaking at 151.9°C–178°C. The natural gas in the Middle Permian of the Central Sichuan Basin is predominantly sourced from the Lower Cambrian Qiongzhusi Formation mudstone and partially from the source rocks of the Middle Permian, indicating a significant source-reservoir conduit of the strike-slip faults in the basin center. The findings provide considerable baseline data to advance further research in the Sichuan Basin.</p

Drivers of High Concentrations of Secondary Organic Aerosols in Northern China during the COVID-19 Lockdowns

During the COVID-19 lockdown in early 2020, observations in Beijing indicate that secondary organic aerosol (SOA) concentrations increased despite substantial emission reduction, but the reasons are not fully explained. Here, we integrate the two-dimensional volatility basis set into a state-of-the-art chemical transport model, which unprecedentedly reproduces organic aerosol (OA) components resolved by the positive matrix factorization based on aerosol mass spectrometer observations. The model shows that, for Beijing, the emission reduction during the lockdown lowered primary organic aerosol (POA)/SOA concentrations by 50%/18%, while deteriorated meteorological conditions increased them by 30%/119%, resulting in a net decrease in the POA concentration and a net increase in the SOA concentration. Emission reduction and meteorological changes both led to an increased OH concentration, which accounts for their distinct effects on POA and SOA. SOA from anthropogenic volatile organic compounds and organics with lower volatility contributed 28 and 62%, respectively, to the net SOA increase. Different from Beijing, the SOA concentration decreased in southern Hebei during the lockdown because of more favorable meteorology. Our findings confirm the effectiveness of organic emission reductions and meanwhile reveal the challenge in controlling SOA pollution that calls for large organic precursor emission reductions to rival the adverse impact of OH increase

Fostering a Holistic Understanding of the Full Volatility Spectrum of Organic Compounds from Benzene Series Precursors through Mechanistic Modeling

A comprehensive understanding of the full volatility spectrum of organic oxidation products from the benzene series precursors is important to quantify the air quality and climate effects of secondary organic aerosol (SOA) and new particle formation (NPF). However, current models fail to capture the full volatility spectrum due to the absence of important reaction pathways. Here, we develop a novel unified model framework, the integrated two-dimensional volatility basis set (I2D-VBS), to simulate the full volatility spectrum of products from benzene series precursors by simultaneously representing first-generational oxidation, multigenerational aging, autoxidation, dimerization, nitrate formation, etc. The model successfully reproduces the volatility and O/C distributions of oxygenated organic molecules (OOMs) as well as the concentrations and the O/C of SOA over wide-ranging experimental conditions. In typical urban environments, autoxidation and multigenerational oxidation are the two main pathways for the formation of OOMs and SOA with similar contributions, but autoxidation contributes more to low-volatility products. NOx can reduce about two-thirds of OOMs and SOA, and most of the extremely low-volatility products compared to clean conditions, by suppressing dimerization and autoxidation. The I2D-VBS facilitates a holistic understanding of full volatility product formation, which helps fill the large gap in the predictions of organic NPF, particle growth, and SOA formation