ABSTRACT
This research analyzes the impact of education quality on GDP per capita and educational access, using instrumental variables (IV) models. The findings shed light on the potential of education investment to foster economic growth and development, highlighting the importance of targeted interventions, teacher training, and data-driven approaches to improve educational outcomes and reduce access disparities. Policymakers and international organizations can utilize these insights to devise strategies aligned with Sustainable Development Goal 4 (SDG 4) of ensuring inclusive and equitable education for all, potentially contributing to the achievement of this crucial goal.
ABSTRACT
Detection of endogenous peptides, especially those with modifications (such as phosphorylation) in biofluids, can serve as an indicator of intracellular pathophysiology. Although great progress has been made in phosphoproteomics in recent years, endogenous phosphopeptidomics has largely lagged behind. One main hurdle in endogenous phosphopeptidomics analysis is the coexistence of proteins and highly abundant nonmodified peptides in complex matrices. In this study, we developed an approach using zirconium(IV)-grafted mesoporous beads to enrich phosphopeptides, followed by analysis with a high resolution nanoRPLC-MS/MS system. The bifunctional material was first tested with digests of standard phosphoproteins and HeLa cell lysates, with excellent enrichment performance achieved. Given the size exclusion nature, the beads were directly applied for endogenous phosphopeptidomic analysis of serum samples from pancreatic ductal adenocarcinoma (PDAC) patients and controls. In total, 329 endogenous phosphopeptides (containing 113 high confidence sites) were identified across samples, by far the largest endogenous phosphopeptide data set cataloged to date. In addition, the method was readily applied for phosphoproteomics of the same set of samples, with 172 phosphopeptides identified and significant changes in dozens of phosphopeptides observed. Given the simplicity and robustness of the proposed method, we envision that it can be readily used for comprehensive phosphorylation studies of serum and other biofluid samples.
Subject(s)
Phosphopeptides , Silicon Dioxide , Zirconium , Zirconium/chemistry , Humans , Silicon Dioxide/chemistry , Phosphopeptides/blood , Phosphopeptides/analysis , Phosphopeptides/chemistry , Porosity , HeLa Cells , Proteomics/methods , Tandem Mass SpectrometryABSTRACT
This research investigates the long-term determinants of carbon emissions in three diverse regions-Europe and Central Asia (ECA), Sub-Saharan Africa (SSA), and the Middle East and North Africa (MENA)-spanning 1990 to 2020. Utilizing advanced econometric models and analyses, including the Regularized Common Correlated Effects Estimator (rCCE), Common Correlated Effects Estimator (CCE), and Mean-Group (MG) approach, the study explores the intricate relationships between carbon emissions, crop production, emissions per agricultural production, energy consumption, renewable energy consumption, per capita GDP, and population. Region-specific nuances are uncovered, highlighting the varying dynamics: ECA exhibits intricate and non-significant relationships, SSA showcases significant effects of population dynamics and green technology adoption, and the MENA region reveals a nuanced interplay between emissions per agricultural production.The findings underscore the universal efficacy of green technology adoption for mitigation. Strategies for mitigating carbon emissions in the agricultural sector require diversified energy transition approaches, emphasizing efficiency enhancements, green technology adoption, and tailored population management strategies based on regional intricacies. Counterfactual simulations indicate the potential efficacy of strategic measures targeting crop production to reduce carbon emissions, while acknowledging the nuanced relationship between economic growth and emissions. Policymakers are urged to recognize the persistence in emission patterns, emphasizing the importance of targeted interventions to transition towards more sustainable trajectories. Overall, the research provides essential insights for crafting effective policies at both regional and global scales to address the complexities of climate change mitigation in the agricultural sector.
Subject(s)
Climate Change , Crop Production , Crop Production/methods , Agriculture/methods , Crops, Agricultural/growth & development , Middle East , Europe , Environmental Monitoring/methods , Africa South of the Sahara , Africa, Northern , Environmental Policy , Asia, CentralABSTRACT
Despite continuous technological improvements in sample preparation, mass-spectrometry-based proteomics for trace samples faces the challenges of sensitivity, quantification accuracy, and reproducibility. Herein, we explored the applicability of turboDDA (a method that uses data-dependent acquisition without dynamic exclusion) for quantitative proteomics of trace samples. After systematic optimization of acquisition parameters, we compared the performance of turboDDA with that of data-dependent acquisition with dynamic exclusion (DEDDA). By benchmarking the analysis of trace unlabeled human cell digests, turboDDA showed substantially better sensitivity in comparison with DEDDA, whether for unfractionated or high pH fractionated samples. Furthermore, through designing an iTRAQ-labeled three-proteome model (i.e., tryptic digest of protein lysates from yeast, human, and E. coli) to document the interference effect, we evaluated the quantification interference, accuracy, reproducibility of iTRAQ labeled trace samples, and the impact of PIF (precursor intensity fraction) cutoff for different approaches (turboDDA and DEDDA). The results showed that improved quantification accuracy and reproducibility could be achieved by turboDDA, while a more stringent PIF cutoff resulted in more accurate quantification but less peptide identification for both approaches. Finally, the turboDDA strategy was applied to the differential analysis of limited amounts of human lung cancer cell samples, showing great promise in trace proteomics sample analysis.
Subject(s)
Proteome , Tandem Mass Spectrometry , Humans , Proteome/analysis , Tandem Mass Spectrometry/methods , Escherichia coli/metabolism , Reproducibility of Results , PeptidesABSTRACT
Diabetes mellitus is the leading cause of cardiovascular and renal disease in the United -States. Despite the beneficial interventions available for patients with diabetes, there remains a need for additional therapeutic targets and therapies in diabetic kidney disease (DKD). Inflammation and oxidative stress are increasingly recognized as important causes of renal diseases. Inflammation is closely associated with mitochondrial damage. The molecular connection between inflammation and mitochondrial metabolism remains to be elucidated. Recently, nicotinamide adenine nucleotide (NAD+) metabolism has been found to regulate immune function and inflammation. In the present studies, we tested the hypothesis that enhancing NAD metabolism could prevent inflammation in and progression of DKD. We found that treatment of db/db mice with type 2 diabetes with nicotinamide riboside (NR) prevented several manifestations of kidney dysfunction (i.e., albuminuria, increased urinary kidney injury marker-1 (KIM1) excretion, and pathologic changes). These effects were associated with decreased inflammation, at least in part via inhibiting the activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway. An antagonist of the serum stimulator of interferon genes (STING) and whole-body STING deletion in diabetic mice showed similar renoprotection. Further analysis found that NR increased SIRT3 activity and improved mitochondrial function, which led to decreased mitochondrial DNA damage, a trigger for mitochondrial DNA leakage which activates the cGAS-STING pathway. Overall, these data show that NR supplementation boosted NAD metabolism to augment mitochondrial function, reducing inflammation and thereby preventing the progression of diabetic kidney disease.
Subject(s)
Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Mice , Animals , Diabetic Nephropathies/metabolism , NAD/metabolism , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Type 2/metabolism , Mitochondria/metabolism , DNA, Mitochondrial/metabolism , Nucleotidyltransferases/metabolism , Inflammation/metabolism , Interferons/metabolismABSTRACT
This study assessed the machine learning based sensitivity analysis coupled with source-apportionment of volatile organic carbons (VOCs) to look into new insights of O3 pollution in Yunlin County located in central-west region of Taiwan. One-year (Jan 1 to Dec 31, 2021) hourly mass concentrations data of 54 VOCs, NOX, and O3 from 10 photochemical assessment monitoring stations (PAMs) in and around the Yunlin County were analyzed. The novelty of the study lies in the utilization of artificial neural network (ANN) to evaluate the contribution of VOCs sources in O3 pollution in the region. Firstly, the station specific source-apportionment of VOCs were carried out using positive matrix factorization (PMF)-resolving six sources viz. AAM: aged air mass, CM: chemical manufacturing, IC: Industrial combustion, PP: petrochemical plants, SU: solvent use and VE: vehicular emissions. AAM, SU, and VE constituted cumulatively more than 65% of the total emission of VOCs across all 10 PAMs. Diurnal and spatial variability of source-segregated VOCs showed large variations across 10 PAMs, suggesting for distinctly different impact of contributing sources, photo-chemical reactivity, and/or dispersion due to land-sea breezes at the monitoring stations. Secondly, to understand the contribution of controllable factors governing the O3 pollution, the output of VOCs source-contributions from PMF model along with mass concentrations of NOX were standardized and first time used as input variables to ANN, a supervised machine learning algorithm. ANN analysis revealed following order of sensitivity in factors governing the O3 pollution: VOCs from IC > AAM > VE ≈ CM ≈ SU > PP ≈ NOX. The results indicated that VOCs associated with IC (VOCs-IC) being the most sensitive factor which need to be regulated more efficiently to quickly mitigate the O3 pollution across the Yunlin County.
Subject(s)
Air Pollutants , Ozone , Volatile Organic Compounds , Ozone/analysis , Air Pollutants/analysis , Taiwan , Environmental Monitoring/methods , Volatile Organic Compounds/analysis , Vehicle Emissions/analysis , Machine Learning , ChinaABSTRACT
A biopsy is usually used to remove a piece of tissue from a patient for laboratory testing. The interstitial fluid is taken out at the same time as the tissue sample. Since interstitial fluid flows between cells and capillaries in tissues, similar to blood plasma, it is necessary to separate interstitial fluid from tissues in order to study them separately. Vacuum blood sampling has been used to draw blood into vacuum-sealed tubes, while interstitial fluid can be removed directly from the skin using microneedles with standard pumps. However, no methods are available to separate blood or interstitial fluid from the tissue itself for molecular characterization. In this study, we designed a biomedical device that can separate interstitial fluid from tissue using a vacuum-assisted filtration method. The device has a chamber that collects fluid extracted from the tissue that remains on top of the filter. We characterized the weight change and glycan profiles of tissues before and after vacuum-assisted filtration. The results demonstrate that the biomedical device can remove interstitial fluid and facilitate the analysis of tissue-specific molecules while minimizing information from the interstitial fluid.
Subject(s)
Capillaries , Extracellular Fluid , Humans , Vacuum , Biopsy , VeinsABSTRACT
AIMS: Nucleotide de novo synthesis is essential to cell growth and survival, and its dysregulation leads to cancers and drug resistance. However, how this pathway is dysregulated in cancer has not been well clarified. This study aimed to identify the regulatory mechanisms of nucleotide de novo synthesis and drug resistance. METHODS: By combining the ChIP-Seq data from the Cistrome Data Browser, RNA sequencing (RNA-Seq) and a luciferase-based promoter assay, we identified transcription factor FOXK2 as a regulator of nucleotide de novo synthesis. To explore the biological functions and mechanisms of FOXK2 in cancers, we conducted biochemical and cell biology assays in vitro and in vivo. Finally, we assessed the clinical significance of FOXK2 in hepatocellular carcinoma. RESULTS: FOXK2 directly regulates the expression of nucleotide synthetic genes, promoting tumor growth and cancer cell resistance to chemotherapy. FOXK2 is SUMOylated by PIAS4, which elicits FOXK2 nuclear translocation, binding to the promoter regions and transcription of nucleotide synthetic genes. FOXK2 SUMOylation is repressed by DNA damage, and elevated FOXK2 SUMOylation promotes nucleotide de novo synthesis which causes resistance to 5-FU in hepatocellular carcinoma. Clinically, elevated expression of FOXK2 in hepatocellular carcinoma patients was associated with increased nucleotide synthetic gene expression and correlated with poor prognoses for patients. CONCLUSION: Our findings establish FOXK2 as a novel regulator of nucleotide de novo synthesis, with potentially important implications for cancer etiology and drug resistance.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/genetics , Cell Proliferation , Liver Neoplasms/drug therapy , Liver Neoplasms/geneticsABSTRACT
As an essential modification, O-linked ß-N-acetylglucosamine (O-GlcNAc) modulates the functions of many proteins. However, site-specific characterization of O-GlcNAcylated proteins remains challenging. Herein, an innovative material grafted with nitro-oxide (NâO) groups was designed for high affinity enrichment for O-GlcNAc peptides from native proteins. By testing with synthetic O-GlcNAc peptides and standard proteins, the synthesized material exhibited high affinity and selectivity. Based on the material prepared, we developed a workflow for site-specific analysis of O-GlcNAcylated proteins in complex samples. We performed O-GlcNAc proteomics with the PANC-1 cell line, a representative model for pancreatic ductal adenocarcinoma. In total 364 O-GlcNAc peptides from 267 proteins were identified from PANC-1 cells. Among them, 183 proteins were newly found to be O-GlcNAcylated in humans (with 197 O-GlcNAc sites newly reported). The materials and methods can be facilely applied for site-specific O-GlcNAc proteomics in other complex samples.
Subject(s)
Acetylglucosamine , Nanospheres , Humans , Acetylglucosamine/analysis , Acetylglucosamine/chemistry , Acetylglucosamine/metabolism , Hydrogen Bonding , Oxides , Proteins , PeptidesABSTRACT
Protein glycosylation plays crucial roles in the regulation of diverse biological processes. As a critical step, mass spectrometry-based site-specific analysis of protein glycosylation is important to better understand these events. Despite the great progress, characterization of structural isomers of glycans and glycopeptides remains challenging. In typical glycoproteomic analysis, collision-induced dissociation (CID) or higher-energy collisional dissociation (HCD) fragmentation produces abundant saccharide oxonium ions containing N-acetylhexosamine (HexNAc) residues. However, it has been difficult to distinguish isobaric GalNAc and GlcNAc modifications by using mass spectrometry only. By using intensities of oxonium ions of standard O-GlcNAc/O-GalNAc peptides, we systematically investigated the fragmentation patterns of different ions. Then a binary logistic regression model was established by training comprehensive data sets from glycoproteomics studies reported. The model was then tested with independent O-glycoproteomics data sets, with reliable classification achieved (>87% accuracy). In comparison to empirical observations and criteria used previously, our model is accurate and generalized. Based on this model, a corresponding Web server HexNAcQuest has been constructed, which is freely accessible to users. The model can also be easily integrated in MS-based glycoproteomics workflows to distinguish the isobaric HexNAc modifications.
Subject(s)
Glycopeptides , Tandem Mass Spectrometry , Glycopeptides/chemistry , Glycosylation , Peptides/metabolism , Polysaccharides/chemistry , Tandem Mass Spectrometry/methodsABSTRACT
Post-translational modification with O-linked ß-N-acetylglucosamine (O-GlcNAc), a process referred to as O-GlcNAcylation, occurs on a vast variety of proteins. Mounting evidence in the past several decades has clearly demonstrated that O-GlcNAcylation is a unique and ubiquitous modification. Reminiscent of a code, protein O-GlcNAcylation functions as a crucial regulator of nearly all cellular processes studied. The primary aim of this review is to summarize the developments in our understanding of myriad protein substrates modified by O-GlcNAcylation from a systems perspective. Specifically, we provide a comprehensive survey of O-GlcNAcylation in multiple species studied, including eukaryotes (e.g., protists, fungi, plants, Caenorhabditis elegans, Drosophila melanogaster, murine, and human), prokaryotes, and some viruses. We evaluate features (e.g., structural properties and sequence motifs) of O-GlcNAc modification on proteins across species. Given that O-GlcNAcylation functions in a species-, tissue-/cell-, protein-, and site-specific manner, we discuss the functional roles of O-GlcNAcylation on human proteins. We focus particularly on several classes of relatively well-characterized human proteins (including transcription factors, protein kinases, protein phosphatases, and E3 ubiquitin-ligases), with representative O-GlcNAc site-specific functions presented. We hope the systems view of the great endeavor in the past 35 years will help demystify the O-GlcNAc code and lead to more fascinating studies in the years to come.
Subject(s)
Acetylglucosamine , Protein Processing, Post-Translational , Animals , Humans , Mice , Acetylglucosamine/chemistry , Drosophila melanogaster/metabolism , Ligases/metabolism , Protein Kinases/metabolism , Transcription Factors/metabolism , Ubiquitins/metabolism , Caenorhabditis elegansABSTRACT
The growing evidence over the past few decades has indicated that the photodynamic antitumor activity of transition metal complexes, and Re(I) compounds are potential candidates for photodynamic therapy. This study reports the synthesis, characterization, and anti-tumor activity of three new Re(I)-guadinium complexes. Cytotoxicity tests reveal that complex Re1 increased cytotoxicity by 145-fold from IC50 > 180 µM in the dark to 1.3 ± 0.7 µM following 10â¯min of light irradiation (425 nm) in HeLa cells. Further, the mechanism by which Re1 induces apoptosis in the presence or absence of light irradiation was investigated, and results indicate that cell death was caused through different pathways. Upon irradiation, Re1 first accumulates on the cell membrane and interacts with death receptors to activate the extrinsic death receptor-mediated signaling pathway, and then is transported into the cell cytoplasm. Most of the intracellular Re1 locates within mitochondria, improving the reactive oxygen species level, and decreasing mitochondrial membrane potential and ATP levels, and inducing the activation of caspase-9 and, thus, apoptosis. Subsequently, the residual Re1 can translocate into the cell nucleus, and activates the p53 pathway, causing cell cycle arrest and eventually cell death.
Subject(s)
Photosensitizing Agents , Rhenium , Apoptosis , Cell Cycle Checkpoints , Cell Line, Tumor , Guanidine/pharmacology , HeLa Cells , Humans , Membrane Potential, Mitochondrial , Mitochondria/metabolism , Photosensitizing Agents/metabolism , Photosensitizing Agents/pharmacology , Reactive Oxygen Species/metabolism , Receptors, Death Domain/metabolism , Rhenium/pharmacologyABSTRACT
It has been a challenge to analyze minute amounts of proteomic samples in a facile and robust manner. Herein, we developed a quantitative proteomics workflow by integrating suspension trapping (S-Trap)-based sample preparation and label-free data-independent acquisition (DIA) mass spectrometry and then applied it for the analysis of microgram and even nanogram amounts of exosome samples. S-Trap-based sample preparation outperformed the traditional in-solution digestion-based approach and the commonly used filter-aided sample preparation (FASP)-based approach with regard to the number of proteins and peptides identified. Moreover, S-Trap-based sample preparation coupled with DIA mass spectrometry also showed the highest reproducibility for protein quantification. In addition, this approach allowed for identification and quantification of exosome proteins with low starting amounts (down to 50 ~ 200 ng). Finally, the proposed method was successfully applied to label-free quantification of exosomal proteins extracted from MDA-MB-231 breast cancer cells and MCF-10A non-tumorigenic epithelial breast cells. Prospectively, we envision the integrated S-Trap sample preparation coupled with DIA quantification strategy as a promising alternative for highly efficient and sensitive analysis of trace amounts of proteomic samples (e.g., exosomal samples).
Subject(s)
Proteomics , Specimen Handling , Mass Spectrometry , Proteins/analysis , Proteome/analysis , Proteomics/methods , Reproducibility of Results , Specimen Handling/methodsABSTRACT
Interactions between proteins are essential to any cellular process and constitute the basis for molecular networks that determine the functional state of a cell. With the technical advances in recent years, an astonishingly high number of protein-protein interactions has been revealed. However, the interactome of O-linked N-acetylglucosamine transferase (OGT), the sole enzyme adding the O-linked ß-N-acetylglucosamine (O-GlcNAc) onto its target proteins, has been largely undefined. To that end, we collated OGT interaction proteins experimentally identified in the past several decades. Rigorous curation of datasets from public repositories and O-GlcNAc-focused publications led to the identification of up to 929 high-stringency OGT interactors from multiple species studied (including Homo sapiens, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Arabidopsis thaliana, and others). Among them, 784 human proteins were found to be interactors of human OGT. Moreover, these proteins spanned a very diverse range of functional classes (e.g., DNA repair, RNA metabolism, translational regulation, and cell cycle), with significant enrichment in regulating transcription and (co)translation. Our dataset demonstrates that OGT is likely a hub protein in cells. A webserver OGT-Protein Interaction Network (OGT-PIN) has also been created, which is freely accessible.
Subject(s)
Acetylglucosamine/metabolism , Data Curation/methods , Databases, Protein/statistics & numerical data , N-Acetylglucosaminyltransferases/metabolism , Protein Interaction Maps , Protein Processing, Post-Translational , Animals , Arabidopsis Proteins/metabolism , Drosophila Proteins/metabolism , Humans , Mice , RatsABSTRACT
Protein O-linked ß-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) is a unique monosaccharide modification discovered in the early 1980s. With the technological advances in the past several decades, great progress has been made to reveal the biochemistry of O-GlcNAcylation, the substrates of O-GlcNAcylation, and the functional importance of protein O-GlcNAcylation. As a nutrient sensor, protein O-GlcNAcylation plays important roles in almost all biochemical processes examined. Although the functional importance of O-GlcNAcylation of proteins has been extensively reviewed previously, the chemical and biochemical aspects have not been fully addressed. In this review, by critically evaluating key publications in the past 35 years, we aim to provide a comprehensive understanding of this important post-translational modification (PTM) from analytical and biochemical perspectives. Specifically, we will cover (1) multiple analytical advances in the characterization of O-GlcNAc cycling components (i.e., the substrate donor UDP-GlcNAc, the two key enzymes O-GlcNAc transferase and O-GlcNAcase, and O-GlcNAc substrate proteins), (2) the biochemical characterization of the enzymes with a variety of chemical tools, and (3) exploration of O-GlcNAc cycling and its modulating chemicals as potential biomarkers and therapeutic drugs for diseases. Last but not least, we will discuss the challenges and possible solutions for basic and translational research of protein O-GlcNAcylation in the future.
Subject(s)
Acetylglucosamine/metabolism , N-Acetylglucosaminyltransferases/metabolism , beta-N-Acetylhexosaminidases/metabolism , Acetylglucosamine/chemistry , Humans , N-Acetylglucosaminyltransferases/chemistry , beta-N-Acetylhexosaminidases/chemistryABSTRACT
O-linked ß-N-acetylglucosamine (O-GlcNAc) is a post-translational modification (i.e., O-GlcNAcylation) on the serine/threonine residues of proteins. As a unique intracellular monosaccharide modification, protein O-GlcNAcylation plays important roles in almost all biochemical processes examined. Aberrant O-GlcNAcylation underlies the etiologies of a number of chronic diseases. With the tremendous improvement of techniques, thousands of proteins along with their O-GlcNAc sites have been reported. However, until now, there are few databases dedicated to accommodate the rapid accumulation of such information. Thus, O-GlcNAcAtlas is created to integrate all experimentally identified O-GlcNAc sites and proteins. O-GlcNAcAtlas consists of two datasets (Dataset-I and Dataset-II, for unambiguously identified sites and ambiguously identified sites, respectively), representing a total number of 4571 O-GlcNAc modified proteins from all species studied from 1984 to 31 Dec 2019. For each protein, comprehensive information (including species, sample type, gene symbol, modified peptides and/or modification sites, site mapping methods and literature references) is provided. To solve the heterogeneity among the data collected from different sources, the sequence identity of these reported O-GlcNAc peptides are mapped to the UniProtKB protein entries. To our knowledge, O-GlcNAcAtlas is a highly comprehensive and rigorously curated database encapsulating all O-GlcNAc sites and proteins identified in the past 35 years. We expect that O-GlcNAcAtlas will be a useful resource to facilitate O-GlcNAc studies and computational analyses of protein O-GlcNAcylation. The public version of the web interface to the O-GlcNAcAtlas can be found at http://oglcnac.org/.
Subject(s)
Acetylglucosamine , Proteins , Acetylglucosamine/metabolism , N-Acetylglucosaminyltransferases/metabolism , Peptides/metabolism , Protein Processing, Post-Translational , Proteins/chemistry , Threonine/metabolismABSTRACT
A simple, accurate, and highly sensitive analytical method was developed in this study for the determination of ten ß-agonists and five ß-blockers in milk. In this method, new adsorbent phosphonic acid-functionalized porous organic polymers were synthesized through a direct knitting method. The synthesis procedure of the materials and the extraction conditions (such as the composition of loading buffer and eluent) were optimized. Benefitting from the high surface area (545-804 m2 g-1), multiple functional framework and good porosity, the phosphonic acid-functionalized porous organic polymers showed a high adsorption rate and high adsorption capacity for ß-agonists (224 mg g-1 and 171 mg g-1 for clenbuterol and ractopamine, respectively). The analytes were quantified by ultra-high-performance liquid chromatography coupled to high-resolution tandem mass spectrometry. It showed a good linearity (with R 2 ranging from 0.9950 to 0.9991 in the linear range of 3-5 orders of magnitude), with low limits of quantification ranging from 0.05 to 0.25 ng g-1. The limits of detection of the method for the analytes were measured to be in the range of 0.02 to 0.1 ng g-1. The recoveries of target analytes from real samples on the material were in the range of 62.4-119.4% with relative standard deviations of 0.6-12.1% (n = 4). Moreover, good reproducibility of the method was obtained with the interday RSD being lower than 11.7% (n = 5) and intraday RSD lower than 12.2% (n = 4). The proposed method was accurate, reliable and convenient for the simultaneous analysis of multiple ß-agonists and ß-blockers. Finally, the method was successfully applied for the analysis of such compounds in milk samples.
ABSTRACT
The prevalence of cognitive impairments and circadian disturbances increases in the elderly and Alzheimer's disease (AD) patients. This study investigated the effects of a standardized extract of Asparagus officinalis stem, ETAS® on cognitive impairments and circadian rhythm status in senescence-accelerated mice prone 8 (SAMP8). ETAS® consists of two major bioactive constituents: 5-hydroxymethyl-2-furfural (HMF), an abundant constituent, and (S)-asfural, a novel constituent, which is a derivative of HMF. Three-month-old SAMP8 male mice were divided into a control, 200 and 1000 mg/kg BW ETAS® groups, while senescence-accelerated resistant mice (SAMR1) were used as the normal control. After 12-week feeding, ETAS® significantly enhanced cognitive performance by an active avoidance test, inhibited the expressions of amyloid-beta precursor protein (APP) and BACE-1 and lowered the accumulation of amyloid ß (Aß) in the brain. ETAS® also significantly increased neuron number in the suprachiasmatic nucleus (SCN) and normalized the expressions of the melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2). In conclusion, ETAS® enhances the cognitive ability, inhibits Aß deposition and normalizes circadian rhythm signaling, suggesting it is beneficial for preventing cognitive impairments and circadian rhythm disturbances in aging.
Subject(s)
Amyloid Precursor Protein Secretases/metabolism , Amyloid beta-Peptides/metabolism , Asparagus Plant/chemistry , Aspartic Acid Endopeptidases/metabolism , Plant Extracts/pharmacology , Receptor, Melatonin, MT1/metabolism , Receptor, Melatonin, MT2/metabolism , Amyloid Precursor Protein Secretases/genetics , Animals , Aspartic Acid Endopeptidases/genetics , Circadian Rhythm , Cognition/drug effects , Gene Expression Regulation/drug effects , Male , Mice , Mice, Inbred Strains , Plant Extracts/chemistry , Receptor, Melatonin, MT2/geneticsABSTRACT
An effective method based on ultra-high performance liquid chromatography-triple quadrupole/electrostatic field orbitrap mass spectrometry (UHPLC-Q-Orbitrap MS) was developed for high-throughput screening and quantitative analysis of 112 pharmaceutical and personal care products (PPCPs) in water. The water samples were separately extracted under alkaline and acidic conditions and cleaned on an SPE column (Cleanert PEP-2). The sample was separated and detected by UHPLC-Q-Orbitrap MS, and the data were collected in full MS scan/date dependent MS2 mode. All the 112 PPCPs in water were qualitatively screened and quantified on the basis of the peak area of the precursor ion. The PPCPs showed a good linear response in the mass concentration range of three orders of magnitude (r2 ≥ 0.9901), and the limits of quantification were between 0.002 µg/L and 0.8 µg/L. The recoveries of 60.1%-129.5% were achieved at different spiked levels of 0.2, 0.4, and 0.8 µg/L, and the RSDs were 1.1%-17.8% (n=6). Moreover, the method was used to screen the PPCPs in water samples acquired from seven regions of Dalian city (China), and 16 PPCPs were identified and quantified. Therefore, this simple method with high sensitivity and wide screening range can be applied to water quality management and environmental risk monitoring.