Abstract Studying the carbon effect of land use in watersheds is important for mitigating global warming, promoting coordinated emission reduction in different regions within the watersheds, and ...realizing high-quality development of the watersheds. Although a number of scholars have carried out relevant studies in the past, they mainly focused on carbon emissions, rarely involved the carbon balance formed by carbon sources and sinks, and lacked relevant studies on the development of low-carbon economy sub-region. Based on this, this study takes the Yellow River Basin as an example, explores the spatial and temporal evolution of carbon emissions from land use in counties in the Yellow River Basin from 1980 to 2020, and predicts the spatial pattern of carbon income and expenditure from land use under natural conditions in 2030 and 2060 using the PLUS model; and then superimposes on the main functional area planning, divides 735 counties in the Yellow River Basin into six low-carbon economic development subregions, and analyzes their economic development The model of their economic development is analyzed. The results show that: (1) the spatial and temporal differentiation of land use carbon balance in the Yellow River Basin has changed greatly over the past 40 years, (2) the spatial distribution pattern of land use carbon balance in the natural context in 2030 and 2060 is more similar to that in 1990, (3) the carbon emission reduction potentials and pattern optimization of the different low-carbon economic development subregions differ greatly, and they have different low-carbon economic development patterns. The results of this study provide a theoretical basis for scientifically and rationally formulating economic policies for low-carbon development in the counties of the Yellow River Basin, and also provide an important reference for related studies in other similar basins or regions in the world.
Sophora flavescens are widely used for their pharmacological effects. As its main pharmacological components, alkaloids and flavonoids are distributed in the root tissues wherein molecular mechanisms ...remain elusive. In this study, metabolite profiles are analyzed using metabolomes to obtain biomarkers detected in different root tissues. These biomarkers include alkaloids, phenylpropanoids, and flavonoids. The high-performance liquid chromatography analysis results indicate the differences in principal component contents. Oxymatrine, sophoridine, and matrine contents are the highest in the phloem, whereas trifolirhizin, maackiain, and kushenol I contents are the highest in the xylem. The transcript expression profiles also show tissue specificity in the roots. A total of 52 and 39 transcripts involved in alkaloid and flavonoid syntheses are found, respectively. Among them, the expression levels of LYSA1, LYSA2, AO2, AO6, PMT1, PMT17, PMT34, and PMT35 transcripts are highly and positively correlated with alkaloids contents. The expression levels of 4CL1, 4CL3, 4CL12, CHI5, CHI7, and CHI9 transcripts are markedly and positively correlated with flavonoids contents. Moreover, the quantitative profiles of alkaloids and flavonoids are provided, and the pivotal genes regulating their distribution in S. flavescens are determined. These results contribute to the existing data for the genetic improvement and target breeding of S. flavescens.
Background
The programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) pathway has been shown to be involved in trauma-induced immunosuppression and to influence CD4
+
T cell ...differentiation. MicroRNA (miR)-21 is a critical player in immune responses. However, it remains largely unknown whether miR-21 is regulated by PD-1 and influences CD4
+
T-cell lineage choice after gastric cancer resection.
Methods
In the present study, we analyzed the percentages of T-helper (Th)-17/regulatory T (Treg) cells and PD-1/PD-L1 expression on peripheral blood mononuclear cells (PBMCs) during the perioperative period. We also detected the secretion of interleukin (IL)-17 and transforming growth factor (TGF)-β1 using enzyme-linked immunosorbent assays (ELISAs). Furthermore, PBMCs isolated from patients were transfected with or without adenovirus-short hairpin-PD-1 (Ad-sh-PD1), pre-miR-21 or adenovirus–green fluorescent protein (Ad-GFP), and the percentages of Th17/Treg cells and related transcription factors were measured.
Results
In patients who underwent gastric cancer resection, the number of Th17 cells decreased, whereas the number of Treg cells increased, accompanied by an increased expression of PD-1/PD-L1. In addition, the expression of RORγt and IL-17 decreased, whereas the expression of Foxp3 and TGF-β1 increased. In vitro, silencing PD-1 via Ad-sh-PD1 promoted the expression of miR-21 and increased the percentage of Th17 cells, but decreased the percentage of Treg cells. The overexpression of miR-21 increased the percentage of Th17 cells but decreased the percentage of Treg cells.
Conclusions
Our study demonstrated that gastric cancer resection altered the balance of Th17/Treg cells and increased PD-1/PD-L1 expression. In the in vitro experiments, the transfection of Ad-sh-PD1 ameliorated Th17/Treg cell imbalance partially by increasing the expression of miR-21.
Hydroxypyridinones (HOPOs) have been used in the chelation therapy of iron and actinide metals. Their application in metal-based radiopharmaceuticals has also been increasing in recent years. This ...review article focuses on how multidentate HOPOs can be used in targeted radiometal-based diagnostic and therapeutic radiopharmaceuticals. The general structure of radiometal-based targeted radiopharmaceuticals, a brief description of siderophores, the basic structure and properties of bidentate HOPO, some representative HOPO multidentate chelating agents, radiopharmaceuticals based on HOPO multidentate bifunctional chelators for gallium-68, thorium-227 and zirconium-89, as well as the future prospects of HOPO multidentate bifunctional chelators in other metal-based radiopharmaceuticals are described and discussed in turn. The HOPO metal-based radiopharmaceuticals that have shown good prospects in clinical and preclinical studies are gallium-68, thorium-227 and zirconium-89 radiopharmaceuticals. We expect HOPO multidentate bifunctional chelators to be a very promising platform for building novel targeted radiometal-based diagnostic and therapeutic radiopharmaceuticals.
Heavy metal contamination in herbal medicines is a global threat to human beings especially at levels above known threshold concentrations. The concentrations of five heavy metals cadmium (Cd), lead ...(Pb), arsenic (As), mercury (Hg) and copper (Cu) were investigated using Inductively Coupled Plasma Optical Mass Spectrometry (ICP-MS) with 1773 samples around the world. According to Chinese Pharmacopoeia, 30.51% (541) samples were detected with at least one over-limit metal. The over-limit ratio for Pb was 5.75% (102), Cd at 4.96% (88), As at 4.17% (74), Hg at 3.78% (67), and of Cu, 1.75% (31). For exposure assessment, Pb, Cd, As, and Hg have resulted in higher than acceptable risks in 25 kinds of herbs. The maximal Estimated Daily Intake of Pb in seven herbs, of Cd in five, of Hg in four, and As in three exceeded their corresponding Provisional Tolerable Daily Intakes. In total 25 kinds of herbs present an unacceptable risk as assessed with the Hazard Quotient or Hazard Index. Additionally, the carcinogenic risks were all under acceptable limits. Notably, As posed the highest risk in all indicators including Estimated Daily Intake, Hazard Index, and carcinogenic risks. Therefore further study on enrichment effect of different states of As and special attention to monitoring shall be placed on As related contamination.
Greenhouse vegetable cultivation with substantive manure and fertilizer input on soils with an elevated geochemical background can accumulate trace metals in soils and plants leading to human health ...risks. Studies on trace metal accumulation over a land use shift duration in an elevated geochemical background scenario are lacking. Accumulation characteristics of seven trace metals in greenhouse soil and edible plants were evaluated along with an assessment of the health risk to the consumers. A total of 118 greenhouse surface soils (0–20cm) and 30 vegetables were collected from Kunming City, Yunnan Province, southwestern China, and analyzed for total Cd, Pb, Cu, Zn, As, Hg, and Cr content by ICP-MS and AFS. The trace metals were ordered Cu>Cd>Hg>Zn>Pb>As>Cr in greenhouse soils accumulation level, and the geo-accumulation index suggested the soil more severely polluted with Cd, Cu, Hg and Zn. The greenhouse and open-field soils had significant difference in Cd, Cr and Zn. The duration of shift from paddy to greenhouse land-use significantly influenced trace metal accumulation with a dramatic change during five to ten year greenhouse land-use, and continuous increase of Cd and Hg. A spatial pattern from north to south for Cd and Hg and a zonal pattern for Cu and Zn were found. An anthropogenic source primarily caused trace metal accumulation, where the principal component analysis/multiple linear regression indicated a contribution 61.2%. While the assessment showed no potential risk for children and adults, the hazard health risks index was greater than one for adolescents. The extended duration of land use as greenhouses caused the trace metal accumulation, rotation in land use should be promoted to reduce the health risks.
•Cd, Cu, Hg and Zn were significantly accumulated in greenhouse vegetable soils.•An anthropogenic source primarily caused the trace metal accumulation.•The extended greenhouse planting duration affected the trace metal accumulation.•The elevated geochemical background less influenced the trace metal accumulation.•Adolescents experienced from the potential health risks of vegetable consumption.
•Acrolein induced pyroptosis and suppressed migration in HUVECs.•Acrolein-induced pyroptosis was dependent on the activation of NLRP3 inflammsome.•Acrolein-suppressed cell migration was involved in ...NLRP3 inflammsome and pyroptosis.•ROS-dependent autophagy signal pathway was the main way.•Collapse of ΔΨm was autophagy dependent and damaged mitochondrion accentuated NLRP3 inflammsome and pyroptosis.
Acrolein is a common environmental pollutant that has been linked to cardiovascular diseases, such as atherosclerosis (AS). Increasing evidence demonstrates that acrolein impairs the cardiovascular system by targeting vascular endothelial cells, but the underlying mechanisms haven’t been completely elucidated. In human umbilical vein endothelial cells (HUVECs), we observed that acrolein treatment induced cell reactive oxygen species (ROS) generation, autophagy, pyroptosis and reduced cell migration. In addition, exposure to acrolein resulted in NLRP3 inflammasome activation as evidenced by cleavage of caspase-1 and downstream mature interleukin (IL)-1β and IL-18 secretion. Knockdown of NLRP3 by small interfering RNA remarkably suppressed acrolein-induced pyroptosis and increased cell migration. Moreover, the scavenging ROS relieved the autophagy, NLRP3 inflammasome activation and pyroptosis. Furthermore, the role of autophagy in the acrolein-medicated pyroptosis and cell migration was investigated. In our study, 3-methyladenine (3-MA), an autophagy inhibitor, aggravated NLRP3 inflammasome activation, pyroptosis and decreased cell migration, rapamycin (Rapa), an autophagy inducer, alleviated aforementioned phenomenon under acrolein stress. Besides, we found damaged mitochondrion accentuated NLRP3 inflammasome and pyroptosis in acrolein-treated cells. In conclusion, it is possible that acrolein induced cell pyroptosis and suppressed cell migration via ROS-dependent autophagy. What’s more, NLRP3 inflammasome activation plays a key role in this process.
Nannochloropsis sp. (a kind of green microalga) residue was pyrolyzed without catalyst or with different amount of HZSM-5 catalyst in a fixed bed reactor in nitrogen flow. The effects of pyrolysis ...parameters such as temperature and catalyst-to-material ratio on product yields were studied. The bio-oils obtained were analyzed by elemental, GC–MS and FTIR analysis. The results indicated that the bio-oils from catalytic pyrolysis of Nannochloropsis sp. residue (BOCP) had lower oxygen content (19.5wt.%) and higher heating-value (32.7MJkg−1) than those obtained from direct pyrolysis (BODP) which had an oxygen content of 30.1wt.% and heating-value of 24.6MJkg−1. The BODP mainly consisted of long carbon chain compounds with various terminal groups (LCTG), while the BOCP mainly consisted of aromatic hydrocarbons. These properties of bio-oils demonstrated that the Nannochloropsis sp. residue can be used as a renewable energy resource and chemical feedstock.
Lauric acid is a bioactive root exudate component in crown daisy. Mi-flp-18 is a pivotal gene regualting nematode chemotaxis and infection. Lauric acid regulates the nematode chemotaxis and disrupts ...the Mi-flp-18 expression in a concentration-dependent manner
A sensitive and specific bioanalytical method was required to measure the exposure of a LAGA-mutated surrogate mouse IgG2a monoclonal antibody in mouse plasma, but the lack of highly specific ...reagents for the LAGA mutant hindered the development of a ligand-binding assay. Equally problematic is that no sensitive unique tryptic peptides suitable for quantitative mass spectrometric analysis could be identified in the mIgG2a complementarity-determining regions. To overcome these challenges, a trypsin alternative pepsin, an aspartic protease, was systematically investigated for its use in digesting the mutated mIgG2a antibody to allow generation of signature peptides for the bioanalytical quantification purpose. After a series of evaluations, a rapid one-hour pepsin digestion protocol was established for the mutated Fc backbone. Consequently, a new pepsin digestion-based liquid chromatography-tandem mass spectrometry (LC/MS/MS) method was successfully developed to support the mouse pharmacokinetic (PK) sample analysis. In brief, robust and reproducible C-terminal cleavage of both leucine and phenylalanine near the double mutation site of the mutated mIgG2a was accomplished at pH ≤2 and 37°C. Combined with a commercially available rat anti-mIgG2a heavy-chain antibody, the established immunoaffinity LC/MS/MS assay achieved a limit of quantitation of 20 ng/mL in the dynamic range of interest with satisfactory assay precision and accuracy. The successful implementation of this novel approach in discovery PK studies eliminates the need for tedious and costly generation of specific immunocapturing reagents for the LAGA mutants. The approach should be widely applicable for developing popular LAGA mutant-based biological therapeutics.A sensitive and specific bioanalytical method was required to measure the exposure of a LAGA-mutated surrogate mouse IgG2a monoclonal antibody in mouse plasma, but the lack of highly specific reagents for the LAGA mutant hindered the development of a ligand-binding assay. Equally problematic is that no sensitive unique tryptic peptides suitable for quantitative mass spectrometric analysis could be identified in the mIgG2a complementarity-determining regions. To overcome these challenges, a trypsin alternative pepsin, an aspartic protease, was systematically investigated for its use in digesting the mutated mIgG2a antibody to allow generation of signature peptides for the bioanalytical quantification purpose. After a series of evaluations, a rapid one-hour pepsin digestion protocol was established for the mutated Fc backbone. Consequently, a new pepsin digestion-based liquid chromatography-tandem mass spectrometry (LC/MS/MS) method was successfully developed to support the mouse pharmacokinetic (PK) sample analysis. In brief, robust and reproducible C-terminal cleavage of both leucine and phenylalanine near the double mutation site of the mutated mIgG2a was accomplished at pH ≤2 and 37°C. Combined with a commercially available rat anti-mIgG2a heavy-chain antibody, the established immunoaffinity LC/MS/MS assay achieved a limit of quantitation of 20 ng/mL in the dynamic range of interest with satisfactory assay precision and accuracy. The successful implementation of this novel approach in discovery PK studies eliminates the need for tedious and costly generation of specific immunocapturing reagents for the LAGA mutants. The approach should be widely applicable for developing popular LAGA mutant-based biological therapeutics.