RESUMO
The heterogeneity of idiopathic pulmonary fibrosis (IPF) limits its diagnosis and treatment. The association between the pathophysiological features and the serum protein signatures of IPF currently remains unclear. The present study analyzed the specific proteins and patterns associated with the clinical parameters of IPF based on a serum proteomic dataset by data-independent acquisition using MS. Differentiated proteins in sera distinguished patients with IPF into three subgroups in signal pathways and overall survival. Aging-associated signatures by weighted gene correlation network analysis coincidently provided clear and direct evidence that aging is a critical risk factor for IPF rather than a single biomarker. Expression of LDHA and CCT6A, which was associated with glucose metabolic reprogramming, was correlated with high serum lactic acid content in patients with IPF. Cross-model analysis and machine learning showed that a combinatorial biomarker accurately distinguished patients with IPF from healthy individuals with an area under the curve of 0.848 (95% CI = 0.684-0.941) and validated from another cohort and ELISA assay. This serum proteomic profile provides rigorous evidence that enables an understanding of the heterogeneity of IPF and protein alterations that could help in its diagnosis and treatment decisions.
Assuntos
Fibrose Pulmonar Idiopática , Proteômica , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/metabolismo , Fibrose Pulmonar Idiopática/patologia , Proteínas Sanguíneas , Biomarcadores , Chaperonina com TCP-1RESUMO
Idiopathic pulmonary fibrosis (IPF) is a progressive fatal interstitial lung disease without an effective cure. Herein, we explore the role of 3,5,3'-triiodothyronine (T3) administration on lung alveolar regeneration and fibrosis at the single-cell level. T3 supplementation significantly altered the gene expression in fibrotic lung tissues. Immune cells were rapidly recruited into the lung after the injury; there were much more M2 macrophages than M1 macrophages in the lungs of bleomycin-treated mice; and M1 macrophages increased slightly, whereas M2 macrophages were significantly reduced after T3 treatment. T3 enhanced the resolution of pulmonary fibrosis by promoting the differentiation of Krt8+ transitional alveolar type II epithelial cells into alveolar type I epithelial cells and inhibiting fibroblast activation and extracellular matrix production potentially by regulation of Nr2f2. In addition, T3 regulated the crosstalk of macrophages with fibroblasts, and the Pros1-Axl signaling axis significantly facilitated the attenuation of fibrosis. The findings demonstrate that administration of a thyroid hormone promotes alveolar regeneration and resolves fibrosis mainly by regulation of the cellular state and cell-cell communication of alveolar epithelial cells, macrophages, and fibroblasts in mouse lungs in comprehensive ways.
Assuntos
Fibrose Pulmonar Idiopática , Camundongos , Animais , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/metabolismo , Pulmão/patologia , Fibrose , Bleomicina/farmacologia , Fibroblastos/metabolismo , Hormônios Tireóideos/metabolismo , Análise de Sequência de RNARESUMO
The pathological features of pulmonary fibrosis (PF) are the abnormal activation and proliferation of myofibroblasts and the extraordinary deposition of the extracellular matrix (ECM). However, the pathogenesis of PF is still indistinct. In recent years, many researchers have realized that endothelial cells had a crucial role in the development of PF. Studies have demonstrated that about 16% of the fibroblasts in the lung tissue of fibrotic mice were derived from endothelial cells. Endothelial cells transdifferentiated into mesenchymal cells via the endothelial-mesenchymal transition (E(nd)MT), leading to the excessive proliferation of endothelial-derived mesenchymal cells and the accumulation of fibroblasts and ECM. This suggested that endothelial cells, a significant component of the vascular barrier, played an essential role in PF. Herein, this review discusses E(nd)MT and its contribution to the activation of other cells in PF, which could provide new ideas for further understanding the source and activation mechanism of fibroblasts and the pathogenesis of PF.
Assuntos
Fibrose Pulmonar , Camundongos , Animais , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/patologia , Células Endoteliais/patologia , Fibrose , Fibroblastos/patologia , Miofibroblastos/patologia , Fatores de RiscoRESUMO
Networks of organic chemical reactions are important in life and probably played a central part in its origin. Network dynamics regulate cell division, circadian rhythms, nerve impulses and chemotaxis, and guide the development of organisms. Although out-of-equilibrium networks of chemical reactions have the potential to display emergent network dynamics such as spontaneous pattern formation, bistability and periodic oscillations, the principles that enable networks of organic reactions to develop complex behaviours are incompletely understood. Here we describe a network of biologically relevant organic reactions (amide formation, thiolate-thioester exchange, thiolate-disulfide interchange and conjugate addition) that displays bistability and oscillations in the concentrations of organic thiols and amides. Oscillations arise from the interaction between three subcomponents of the network: an autocatalytic cycle that generates thiols and amides from thioesters and dialkyl disulfides; a trigger that controls autocatalytic growth; and inhibitory processes that remove activating thiol species that are produced during the autocatalytic cycle. In contrast to previous studies that have demonstrated oscillations and bistability using highly evolved biomolecules (enzymes and DNA) or inorganic molecules of questionable biochemical relevance (for example, those used in Belousov-Zhabotinskii-type reactions), the organic molecules we use are relevant to metabolism and similar to those that might have existed on the early Earth. By using small organic molecules to build a network of organic reactions with autocatalytic, bistable and oscillatory behaviour, we identify principles that explain the ways in which dynamic networks relevant to life could have developed. Modifications of this network will clarify the influence of molecular structure on the dynamics of reaction networks, and may enable the design of biomimetic networks and of synthetic self-regulating and evolving chemical systems.
Assuntos
Amidas/síntese química , Modelos Químicos , Origem da Vida , Compostos de Sulfidrila/síntese química , Amidas/química , Biomimética , Catálise , Dissulfetos/química , Ésteres/química , Evolução Química , Cinética , Estrutura Molecular , Compostos de Sulfidrila/químicaRESUMO
Isolation and analysis of circulating tumor cells (CTCs) from the blood of patients at risk of metastatic cancers is a promising approach to improving cancer treatment. However, CTC isolation is difficult due to low CTC abundance and heterogeneity. Previously, we reported an ensemble-decision aliquot ranking (eDAR) platform for the rare cell and CTC isolation with high throughput, greater than 90% recovery, and high sensitivity, allowing detection of low surface antigen-expressing cells linked to metastasis. Here we demonstrate a sequential eDAR platform capable of isolating rare cells from whole blood with high purity. This improvement in purity is achieved by using a sequential sorting and flow stretching design in which whole blood is sorted and fluid elements are stretched using herringbone features and the parabolic flow profile being sorted a second time. This platform can be used to collect single CTCs in a multiwell plate for downstream analysis.
Assuntos
Células Sanguíneas , Separação Celular/métodos , Células Neoplásicas Circulantes , Humanos , Dispositivos Lab-On-A-Chip , Células MCF-7 , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodosRESUMO
Protein tyrosine phosphatases (PTPs) contribute to a striking variety of human diseases, yet they remain vexingly difficult to inhibit with uncharged, cell-permeable molecules; no inhibitors of PTPs have been approved for clinical use. This study uses a broad set of biophysical analyses to evaluate the use of abietane-type diterpenoids, a biologically active class of phytometabolites with largely nonpolar structures, for the development of pharmaceutically relevant PTP inhibitors. Results of nuclear magnetic resonance analyses, mutational studies, and molecular dynamics simulations indicate that abietic acid can inhibit protein tyrosine phosphatase 1B, a negative regulator of insulin signaling and an elusive drug target, by binding to its active site in a non-substrate-like manner that stabilizes the catalytically essential WPD loop in an inactive conformation; detailed kinetic studies, in turn, show that minor changes in the structures of abietane-type diterpenoids (e.g., the addition of hydrogens) can improve potency (i.e., lower IC50) by 7-fold. These findings elucidate a previously uncharacterized mechanism of diterpenoid-mediated inhibition and suggest, more broadly, that abietane-type diterpenoids are a promising source of structurally diverse-and, intriguingly, microbially synthesizable-molecules on which to base the design of new PTP-inhibiting therapeutics.
Assuntos
Abietanos/química , Modelos Moleculares , Simulação de Dinâmica Molecular , Inibidores de Proteínas Quinases/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Proteína Tirosina Fosfatase não Receptora Tipo 1/química , Humanos , Ressonância Magnética Nuclear Biomolecular , Domínios Proteicos , Dobramento de ProteínaRESUMO
This paper describes the design and fabrication of a "pop-up" electrochemical paper-based analytical device (pop-up-EPAD) to measure beta-hydroxybutyrate (BHB)-a biomarker for diabetic ketoacidosis-using a commercial combination BHB/glucometer. Pop-up-EPADs are inspired by pop-up greeting cards and children's books. They are made from a single sheet of paper folded into a three-dimensional (3D) device that changes shape, and fluidic and electrical connectivity, by simply folding and unfolding the structure. The reconfigurable 3D structure makes it possible to change the fluidic path and to control timing; it also provides mechanical support for the folded and unfolded structures that enables good registration and repeatability on folding. A pop-up-EPAD designed to detect BHB shows performance comparable to commercially available plastic test strips over the clinically relevant range of BHB in blood when used with a commercial glucometer that integrates the ability to measure glucose and BHB (combination BHB/glucometer). With simple modifications of the electrode and the design of the fluidic path, the pop-up-EPAD also detects BHB in buffer using a simple glucometer-a device that is more available than the combination BHB/glucometer. Strategies that use a "3D pop-up"-that is, large-scale changes in 3D structure and fluidic paths-by folding/unfolding add functionality to EPADs (e.g., controlled timing, fluidic handling and path programming, control over complex sequences of steps, and alterations in electrical connectivity) and should enable the development of new classes of paper-based diagnostic devices.
Assuntos
Ácido 3-Hidroxibutírico/sangue , Técnicas Eletroquímicas/métodos , Papel , Ácido 3-Hidroxibutírico/química , Biomarcadores/sangue , Cetoacidose Diabética/diagnóstico , Técnicas Eletroquímicas/instrumentação , Eletrodos , Humanos , Limite de Detecção , NAD/química , Sistemas Automatizados de Assistência Junto ao LeitoRESUMO
Several technologies recently have been developed for separating and counting circulating tumor cells (CTCs) in the human blood. CTCs play an important role in the metastasis of cancer. Most of the current applications are focused on the enumeration of CTCs; however, analysis of the enumerated CTCs has been proven to be increasingly important. Ensemble-decision aliquot ranking (eDAR) is a high-throughput method that allows the isolation of the CTCs from the whole blood with high recovery and a zero false-positive rate. Coupling a CTC separation and capturing method, such as eDAR, with a downstream immunostaining test provides information about the cell's expression of certain protein biomarkers. In this article, we introduce a semi-automated system for sequential immunolabeling and photobleaching on the eDAR platform. With our new technique, we were able to evaluate the expression of eight different biomarkers on isolated CTCs.
Assuntos
Biomarcadores Tumorais/análise , Células Neoplásicas Circulantes/química , Antígenos CD/análise , Antígenos CD/imunologia , Antígenos de Neoplasias/análise , Antígenos de Neoplasias/imunologia , Automação Laboratorial , Neoplasias da Mama/química , Moléculas de Adesão Celular/análise , Moléculas de Adesão Celular/imunologia , Moléculas de Adesão Celular Neuronais/análise , Moléculas de Adesão Celular Neuronais/imunologia , Separação Celular/métodos , Molécula de Adesão da Célula Epitelial , Receptores ErbB/análise , Receptores ErbB/imunologia , Feminino , Proteínas Fetais/análise , Proteínas Fetais/imunologia , Humanos , Queratinas/análise , Queratinas/imunologia , Células-Tronco Mesenquimais/química , Fotodegradação , Análise de Célula Única/métodos , Coloração e RotulagemRESUMO
Lung cancer is a major public health issue and heavy burden in China and worldwide due to its high incidence and mortality without effective treatment. It's imperative to develop new treatments to overcome drug resistance. Natural products from food source, given their wide-ranging and long-term benefits, have been increasingly used in tumor prevention and treatment. This study revealed that Hibiscus manihot L. flower extract (HML) suppressed the proliferation and migration of A549 cells in a dose and time dependent manner and disrupting cell cycle progression. HML markedly enhanced the accumulation of ROS, stimulated the dissipation of mitochondrial membrane potential (MMP) and that facilitated mitophagy through the loss of mitochondrial function. In addition, HML induced apoptosis by activation of the PTEN-P53 pathway and inhibition of ATG5/7-dependent autophagy induced by PINK1-mediated mitophagy in A549 cells. Moreover, HML exert anticancer effects together with 5-FU through synergistic effect. Taken together, HML may serve as a potential tumor prevention and adjuvant treatment for its functional attributes.
Assuntos
Hibiscus , Neoplasias Pulmonares , Manihot , Humanos , Células A549 , Hibiscus/metabolismo , Manihot/metabolismo , Autofagia , Neoplasias Pulmonares/patologia , Flores/metabolismo , Apoptose , Espécies Reativas de Oxigênio/metabolismoRESUMO
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease of unknown etiology. The emerging evidence demonstrates that metabolic homeostatic imbalance caused by repetitive injuries of the alveolar epithelium is the potential pathogenesis of IPF. Proteomic analysis identified that Acetyl-CoA synthetase short chain family member 3 (ACSS3) expression was decreased in IPF patients and mice with bleomycin-induced fibrosis. ACSS3 participated in lipid and carbohydrate metabolism. Increased expression of ACSS3 downregulated carnitine palmitoyltransferase 1A (CPT-1A) and resulted in the accumulation of lipid droplets, while enhanced glycolysis which led to an increase in extracellular lactic acid levels in A549 cells. ACSS3 increases the production of succinyl-CoA through propionic acid metabolism, and decreases the generation of acetyl-CoA and ATP in alveolar epithelial cells. Overexpression of Acss3 inhibited the excessive deposition of ECM and attenuated the ground-glass opacity which determined by micro-CT in vivo. In a nutshell, our findings demonstrate that ACSS3 decreased the fatty acid oxidation through CPT1A deficiency and enhanced anaerobic glycolysis, this metabolic reprogramming deactivate the alveolar epithelial cells by lessen mitochondrial fission and fusion, increase of ROS production, suppression of mitophagy, promotion of apoptosis, suggesting that ACSS3 might be potential therapeutic target in pulmonary fibrosis.
Assuntos
Fibrose Pulmonar , Animais , Humanos , Camundongos , Acetilcoenzima A , Células Epiteliais/metabolismo , Homeostase , Proteômica , Fibrose Pulmonar/metabolismo , Acetato-CoA Ligase/metabolismoRESUMO
High-sensitivity flow cytometers have been developed for multi-parameter characterization of single extracellular vesicles (EVs), but performance varies among instruments and calibration methods. Here we compare the characterization of identical (split) EV samples derived from human colorectal cancer (DiFi) cells by three high-sensitivity flow cytometers, two commercial instruments, CytoFLEX/CellStream, and a custom single-molecule flow cytometer (SMFC). DiFi EVs were stained with the membrane dye di-8-ANEPPS and with PE-conjugated anti-EGFR or anti-tetraspanin (CD9/CD63/CD81) antibodies for estimation of EV size and surface protein copy numbers. The limits of detection (LODs) for immunofluorescence and vesicle size based on calibration using cross-calibrated, hard-dyed beads were â¼10 PE/â¼80 nm EV diameter for CytoFLEX and â¼10 PEs/â¼67 nm for CellStream. For the SMFC, the LOD for immunofluorescence was 1 PE and ≤ 35 nm for size. The population of EVs detected by each system (di-8-ANEPPS+/PE+ particles) differed widely depending on the LOD of the system; for example, CellStream/CytoFLEX detected only 5.7% and 1.5% of the tetraspanin-labelled EVs detected by SMFC, respectively, and median EV diameter and antibody copy numbers were much larger for CellStream/CytoFLEX than for SMFC as measured and validated using super-resolution/single-molecule TIRF microscopy. To obtain a dataset representing a common EV population analysed by all three platforms, we filtered out SMFC and CellStream measurements for EVs below the CytoFLEX LODs as determined by bead calibration (10 PE/80 nm). The inter-platform agreement using this filtered dataset was significantly better than for the unfiltered dataset, but even better concordance between results was obtained by applying higher cutoffs (21 PE/120 nm) determined by threshold analysis using the SMFC data. The results demonstrate the impact of specifying LODs to define the EV population analysed on inter-instrument reproducibility in EV flow cytometry studies, and the utility of threshold analysis of SMFC data for providing semi-quantitative LOD values for other flow cytometers.
Assuntos
Vesículas Extracelulares , Citometria de Fluxo , Citometria de Fluxo/métodos , Citometria de Fluxo/instrumentação , Humanos , Vesículas Extracelulares/metabolismo , Neoplasias Colorretais/diagnóstico , Linhagem Celular Tumoral , Imagem Individual de Molécula/métodos , Imagem Individual de Molécula/instrumentaçãoRESUMO
Enumeration of circulating tumor cells (CTCs) has proved valuable for early detection and prognosis in cancer treatment. This paper describes an automated high-throughput counting method for CTCs based on microfluidics and line-confocal microscopy. Peripheral blood was directly labeled with multiple antibodies, each conjugated with a different fluorophore, pneumatically pumped through a microfluidic channel, and interrogated by a line-confocal microscope. On the basis of the fluorescence signals and labeling schemes, the count of CTCs was automatically reported. Due to the high flow rate, 1 mL of whole blood can be analyzed in less than 30 min. We applied this method in analyzing CTCs from 90 stage IV breast cancer patient samples and performed a side-by-side comparison with the results of the CellSearch assay, which is the only method approved by the U.S. Food and Drug Administration at present for enumeration of CTCs. This method has a recovery rate for cultured breast cancer cells of 94% (n = 9), with an average of 1.2 counts/mL of background level of detected CTCs from healthy donors. It detected CTCs from breast cancer patients ranging from 15 to 3375 counts/7.5 mL. Using this method, we also demonstrate the ability to enumerate CTCs from breast cancer patients that were positive for Her2 or CD44(+)/CD24(-), which is a putative cancer stem cell marker. This automated method can enumerate CTCs from peripheral blood with high throughput and sensitivity. It could potentially benefit the clinical diagnosis and prognosis of cancer.
Assuntos
Contagem de Células/métodos , Células Neoplásicas Circulantes , Anticorpos/química , Anticorpos/imunologia , Antígenos de Neoplasias/imunologia , Automação , Moléculas de Adesão Celular/imunologia , Contagem de Células/instrumentação , Molécula de Adesão da Célula Epitelial , Corantes Fluorescentes/química , Humanos , Células MCF-7 , Técnicas Analíticas Microfluídicas , Microscopia ConfocalRESUMO
Ensemble-decision aliquot ranking (eDAR) is a sensitive and high-throughput method to analyze circulating tumor cells (CTCs) from peripheral blood. Here, we report the next generation of eDAR, where we designed and optimized a new hydrodynamic switching scheme for the active sorting step in eDAR, which provided fast cell sorting with an improved reproducibility and stability. The microfluidic chip was also simplified by incorporating a functional area for subsequent purification using microslits fabricated by standard lithography method. Using the reported second generation of eDAR, we were able to analyze 1 mL of whole-blood samples in 12.5 min, with a 95% recovery and a zero false positive rate (n = 15).
Assuntos
Separação Celular/métodos , Técnicas Analíticas Microfluídicas/métodos , Células Neoplásicas Circulantes/patologia , Linhagem Celular Tumoral , Humanos , Hidrodinâmica , Metástase Neoplásica , Neoplasias Pancreáticas/patologia , Silício/químicaRESUMO
Natural substances have long been used in cancer treatment, particularly in Chinese or Indian traditional medicine. Natural compounds are defined as chemical molecules that are found in fungus, marine animals, plants, or bacteria and have significant biological and pharmacological effects. Wogonoside and isoliquiritigenin are two well-known examples of plant-derived chemicals. Several modern anti-cancer medications also come from natural sources. The mic test was used to conduct tests on various natural substances' antimicrobial and antifungal properties. MTT assay was used on lung cancer, and normal (HUVEC) cell lines for analyzing of cytotoxicity and anti-lung cancer effects of Wogonoside and Isoliquiritigenin. These Wogonoside and Isoliquiritigenin had high cell death and anti-lung cancer effects against SPC-A-1, SK-LU-1, and 95D cell lines. Among the above cell lines, the best result of anti-cancer properties of Wogonoside and Isoliquiritigenin was gained in the cell line of KATO III. We examined the inhibition effects on two important enzymes using these two compounds and determined the results. PnPG and NADPH were used as substrates for enzymes. IC50 of Wogonoside and Isoliquiritigenin compounds were 18.25±4.18 and 112.64±16.02 nM for α-glucosidase and 54.72±8.61 and 47.12±11.56 nM for sorbitol dehydrogenase, respectively. For Wogonoside, gram-negative bacteria (K. pneumoniae and E. coli) had MIC values of 9.75±0.95 and 13.77±1.43 µg/mL, gram-positive bacteria (E. faecalis and S. aureus) of 37.02±4.52 and 24.85±3.64 µg/mL, respectively. Finally, molecular docking was done for enzyme results and anticancer results. Results of enzymes and antibacterial, antifungal were in level of micromolar that is good impacts. These natural compounds may be anti-diabetic, anticancer, antibacterial candidates for drug design.
Assuntos
Neoplasias Pulmonares , alfa-Glucosidases , Animais , L-Iditol 2-Desidrogenase , Antifúngicos/farmacologia , Simulação de Acoplamento Molecular , Staphylococcus aureus , Escherichia coli , Antibacterianos/farmacologia , Antibacterianos/química , Neoplasias Pulmonares/tratamento farmacológico , Testes de Sensibilidade MicrobianaRESUMO
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease that causes irreversible damage to lung tissue characterized by excessive deposition of extracellular matrix (ECM) and remodeling of lung parenchyma. The current diagnosis of IPF is complex and usually completed by a multidisciplinary team including clinicians, radiologists and pathologists they work together and make decision for an effective treatment, it is imperative to introduce novel practical methods for IPF diagnosis. This study provided a new diagnostic model of idiopathic pulmonary fibrosis based on machine learning. Six genes including CDH3, DIO2, ADAMTS14, HS6ST2, IL13RA2, and IGFL2 were identified based on the differentially expressed genes in IPF patients compare to healthy subjects through a random forest classifier with the existing gene expression databases. An artificial neural network model was constructed for IPF diagnosis based these genes, and this model was validated by the distinctive public datasets with a satisfactory diagnostic accuracy. These six genes identified were significant correlated with lung function, and among them, CDH3 and DIO2 were further determined to be significantly associated with the survival. Putting together, artificial neural network model identified the significant genes to distinguish idiopathic pulmonary fibrosis from healthy people and it is potential for molecular diagnosis of IPF.
Assuntos
Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/genética , Pulmão , SulfotransferasesRESUMO
Idiopathic pulmonary fibrosis is a progressive and fatal interstitial lung disease with a poor prognosis and limited therapeutic options, which is characterized by aberrant myofibroblast activation and pathological remodeling of the extracellular matrix, while the mechanism remains elusive. In the present investigation, we observed a reduction in ADRB2 expression within both IPF and bleomycin-induced fibrotic lung samples, as well as in fibroblasts treated with TGF-ß1. ADRB2 inhibition blunted bleomycin-induced lung fibrosis. Blockage of the ADRB2 suppressed proliferation, migration, and invasion and attenuated TGF-ß1-induced fibroblast activation. Conversely, the enhancement of ADRB2 expression or functionality proved capable of inducing fibroblast-to-myofibroblast differentiation. Subsequent mechanistic investigation revealed that inhibition of ADRB2 suppressed the activation of SMAD2/3 in lung fibroblasts and increased phos-SMAD2/3 proteasome degradation, and vice versa. Finally, ADRB2 inhibition combined with antioxidants showed increased efficacy in the therapy of bleomycin-induced lung fibrosis. In short, these data indicate that ADRB2 is involved in lung fibroblast differentiation, and targeting ADRB2 could emerge as a promising and innovative therapeutic approach for pulmonary fibrosis.
RESUMO
Most flash floods in countries around the world occur in poor rural mountainous areas and typically cause more casualties and economic losses due to monitoring challenges and early warning difficulties. In mountainous regions, reservoir projects are a very effective measure for mitigating the risk of flash floods and can also be used for water supplies and irrigation, but there is a lack of research on the comprehensive benefit assessments of reservoirs. In this paper, we simulate the inundation extents of flash floods for the Wangmo Basin in China, where flash floods frequently occur, under different return periods using the HEC-HMS (HEC-Hydrologic Modelling System) model and FLO-2D model and compare the resulting housing losses with and without reservoirs. The results indicate that using dam and reservoir operations for flood control in the Wangmo River Basin decreases the flooded housing area in the county centre by approximately 12.9 %-30.2 %, which results in housing losses reductions of 19.7 %-45.7 %.These dams and reservoirs will begin to make a profit during the 38th year of operation, and the average annual net benefit reaches 101.76 million RMB in 50 years, which is equivalent to 1.43 % of the GDP of Wangmo County; the net benefits of flood control, water supply and irrigation accounted for 0.4 %, 1.0 % and 0.03 %, respectively. Priority should be given to planning and building these water conservation measures to help these poor mountainous areas. The construction of dams and reservoirs can contribute to decreasing losses in poverty and disaster-prone regions. The effectiveness evaluation framework for dams and reservoirs presented in this study can be applied to other mountainous basins for flood control and local development.
Assuntos
Desastres , Inundações , Inundações/prevenção & controle , Rios , Hidrologia , Abastecimento de Água , ChinaRESUMO
A simple and fast (<5 s) method for in situ arsenic speciation on solid surfaces has been developed based on desorption electrospray ionization-tandem mass spectrometry (DESI-MS). Arsenic-polluted environmental samples such as animal feed and plant tissues could be directly monitored by DESI-MS. Each arsenic species in this study, including monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), arsenobetaine (AsB), arsenocholine (AsC), 4-arsanilic acid (p-ASA), 4-hydroxyphenylarsonic acid (4-OH), Nitarsone, Roxarsone and two inorganic arsenic species, arsenate As(v) and arsenite As(iii), could be detected by their typical m/z and collision induced dissociation (CID) behavior respectively. By the characteristic information, mixtures of different arsenic species could be detected without any sample preparation and separation process. This method could give absolute detection limits of the arsenic species at ng/mm(2) to pg/mm(2) level with a best RSD of 5.3% (n = 5). The method could be potentially applied to in situ environmental monitoring of arsenic pollution, especially that caused by arsenic pesticides, animal feed additives, herbicides and wood treatment.
Assuntos
Arsênio/análise , Poluentes Ambientais/análise , Espectrometria de Massas por Ionização por Electrospray/métodos , Ração Animal/análise , Monitoramento Ambiental , Praguicidas/química , Espectrometria de Massas em TandemRESUMO
A simple and easy-to-build high-throughput analysis system was constructed. The system consisted of three major components: (1) a multichannel device with 16 parallel capillaries, (2) a desorption electrospray ionization (DESI) source, and (3) a linear ion trap mass spectrometer. When analyses were performed, the multichannel device was moved horizontally on a translation stage controlled by a step motor. Our design expands the functions of DESI, in which the liquid sample in capillary was driven out by the nebulizing gas, ionized, and then transferred to a mass spectrometer. To assess the high-throughput performance of the system, 5 mg/L 1,3-diethyl-1,3-diphenylurea (DDU) solution and 10 mg/L angiotensin I solution were alternatively loaded into the reservoirs and capillaries in the multichannel device. Results indicated that analyses of the all the samples in 16 capillaries were completed within 1.6 min, which means a throughput of 600 samples/h. Reactive DESI experiment was also successfully performed with this system to show the feasibility of online derivatization. The relative standard deviations for a single capillary and five identical capillaries were 7.6 (n = 16) and 12.3%, respectively. Linear relative abundance response was achieved for DDU (r = 0.9971).