ABSTRACT
Lithium niobate (LN) photonics has gained significant interest for their distinct material properties. However, achieving monolithically integrated photodetectors on lithium niobate on an insulator (LNOI) platform for communication wavelengths remains a challenge due to the large bandgap and extremely low electrical conductivity of LN material. A two-dimensional (2D) material photodetector is an ideal solution for LNOI photonics with a strong light-matter interaction and simple integration technique. In this work, a van der Waals heterostructure photodiode composed of a p-type black phosphorus layer and an n-type MoS2 layer is successfully demonstrated for photodetection at communication wavelengths on a LNOI platform. The LNOI waveguide-integrated BP-MoS2 photodetector exhibits a dark current as low as 0.21â nA and an on/off ratio exceeding 200 under zero voltage bias with an incident power of 13.93â µW. A responsivity as high as 1.46â A/W is achieved at -1â V bias with a reasonable dark current around 2.33â µA. With the advantages of high responsivity, low dark current, and simple fabrication process, it is promising for the monolithically integrated photodetector application for LNOI photonic platforms at communication wavelengths.
ABSTRACT
Mycoplasma pneumoniae, a notable pathogen behind respiratory infections, employs specialized proteins to adhere to the respiratory epithelium, an essential process for initiating infection. The role of glycosaminoglycans, especially heparan sulfate, is critical in facilitating pathogen-host interactions, presenting a strategic target for therapeutic intervention. In this study, we assembled a glycan library comprising heparin, its oligosaccharide derivatives, and a variety of marine-derived sulfated glycans to screen the potential inhibitors for the pathogen-host interactions. By using Surface Plasmon Resonance spectroscopy, we evaluated the library's efficacy in inhibiting the interaction between M. pneumoniae adhesion proteins and heparin. Our findings offer a promising avenue for developing novel therapeutic strategies against M. pneumoniae infections.
Subject(s)
Heparin , Mycoplasma pneumoniae , Polysaccharides , Mycoplasma pneumoniae/drug effects , Heparin/pharmacology , Heparin/chemistry , Polysaccharides/pharmacology , Polysaccharides/chemistry , Aquatic Organisms , Humans , Adhesins, Bacterial/metabolism , Adhesins, Bacterial/drug effects , Bacterial Adhesion/drug effects , Pneumonia, Mycoplasma/drug therapy , Pneumonia, Mycoplasma/microbiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Animals , Host-Pathogen Interactions , Sulfates/chemistry , Sulfates/pharmacologyABSTRACT
This study established a convenient, rapid, and sensitive ultra-performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of magnoflorine,(R)-coclaurine, vicenin â ¡, isospinosin, spinosin, swertisin, N-nornuciferine, 6î-feruloylspinosin, and jujuboside B in beagle dog plasma after oral administration of fried Ziziphi Spinosae Semen(FZSS) extract. The Waters HSS-T3 C_(18) column(2.1 mm×100 mm, 1.8 µm) was used. The methanol-aqueous solution(containing 0.01% formic acid) was adopted as the mobile phase for gradient elution. The nine components and two internal standards were completely separated within 8 min. The mass spectrometry detection was performed in multiple reaction monitoring(MRM) mode by positive and negative ion switching of electrospray ionization. The analytical method was validated in terms of specificity, selectivity, linear range, accuracy, precision, recovery, matrix effect, and stability. It could meet the requirement of pharmacokinetic research after oral administration of FZSS extract to beagle dogs. The results showed that the time to reach the peak concentration(T_(max)) of magnoflorine,(R)-coclaurine, vicenin â ¡, isospinosin, spinosin, 6î-feruloylspinosin, and jujuboside B was 2.40-3.20 h, and the elimination halflife(t_(1/2)) was 2.08-6.79 h after a single-dose oral administration of FZSS to beagle dogs. The exposure of magnoflorine and spinosin was high, with a peak concentration(C_(max)) of 76.7 and 31.5 ng·mL~(-1) and an area under the curve(AUC_(0-∞)) of 581 and 315 ng·h·mL~(-1), respectively. The exposure of the remaining five compounds was lower, with a C_(max) of 0.81-13.0 ng·mL~(-1) and an AUC_(0-∞) of 6.00-106 ng·h·mL~(-1). This study provides a reference for the follow-up research of FZSS.
Subject(s)
Drugs, Chinese Herbal , Tandem Mass Spectrometry , Ziziphus , Animals , Dogs , Tandem Mass Spectrometry/methods , Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal/pharmacokinetics , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/administration & dosage , Ziziphus/chemistry , Male , Liquid Chromatography-Mass SpectrometryABSTRACT
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide COVID-19 pandemic, leading to 6.8 million deaths. Numerous variants have emerged since its outbreak, resulting in its significantly enhanced ability to spread among humans. As with many other viruses, SARSCoV2 utilizes heparan sulfate (HS) glycosaminoglycan (GAG) on the surface of host cells to facilitate viral attachment and initiate cellular entry through the ACE2 receptor. Therefore, interfering with virion-HS interactions represents a promising target to develop broad-spectrum antiviral therapeutics. Sulfated glycans derived from marine organisms have been proven to be exceptional reservoirs of naturally existing HS mimetics, which exhibit remarkable therapeutic properties encompassing antiviral/microbial, antitumor, anticoagulant, and anti-inflammatory activities. In the current study, the interactions between the receptor-binding domain (RBD) of S-protein of SARS-CoV-2 (both WT and XBB.1.5 variants) and heparin were applied to assess the inhibitory activity of 10 marine-sourced glycans including three sulfated fucans, three fucosylated chondroitin sulfates and two fucoidans derived from sea cucumbers, sea urchin and seaweed Saccharina japonica, respectively. The inhibitory activity of these marine derived sulfated glycans on the interactions between RBD of S-protein and heparin was evaluated using Surface Plasmon Resonance (SPR). The RBDs of S-proteins from both Omicrion XBB.1.5 and wild-type (WT) were found to bind to heparin, which is a highly sulfated form of HS. All the tested marine-sourced sulfated glycans exhibited strong inhibition of WT and XBB.1.5 S-protein binding to heparin. We believe the study on the molecular interactions between S-proteins and host cell glycosaminoglycans provides valuable insight for the development of marine-sourced, glycan-based inhibitors as potential anti-SARS-CoV-2 agents.
Subject(s)
Heparin , Polysaccharides , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , SARS-CoV-2/drug effects , SARS-CoV-2/metabolism , Heparin/pharmacology , Heparin/chemistry , Heparin/metabolism , Polysaccharides/chemistry , Polysaccharides/pharmacology , Polysaccharides/metabolism , Humans , Spike Glycoprotein, Coronavirus/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , COVID-19/virology , COVID-19/metabolism , Protein Binding , Animals , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Heparitin Sulfate/metabolism , Heparitin Sulfate/chemistryABSTRACT
The Forel Ule water color index (FUI) based on satellite inversion can characterize the comprehensive characteristics of water quality on a large spatiotemporal scale. The high-frequency observations and rich historical data of the MODIS surface reflectance product (MODIS-500 m) provide important data support for monitoring the FUI of inland lakes. However, MODIS-500 m has only three bands in the visible light range, resulting in significant uncertainty in FUI inversion. To address this problem, this study developed an improved FUI inversion model using 500 synthetic spectra covering natural waters. The model, with a performance threshold set at 170° (FUI = 8), used a segmented algorithm across the entire color space. Validated with on-site measurement datasets (3500 samples), the model exhibited excellent performance, with mean relative error (MRE) and root mean square error (RMSE) of 1.71 % and 3.63°, respectively. Compared to existing models, it was more suitable for long-term FUI inversion in various types of lakes, particularly in eutrophic regions. Subsequently, the model was applied to MODIS-500 m observations from 2000 to 2022, revealing the spatiotemporal dynamics of FUI in 180 large lakes and reservoirs (hereinafter referred to as lakes) in China. The results indicated that the long-term mean FUI in the study area was 9, with 7 and 12 in the western and eastern regions, respectively, showing a distinct spatial distribution of "blue in the west and green in the east." The mean change rate of hue angle for all lakes was -0.085°/yr, showing an overall decreasing trend. Environmental factors' relative contributions to long-term water color changes in each lake region were quantified using the multiple general linear model (GLM). Although each lake region exhibited different driving forces, they were primarily influenced by vegetation, lake surface area, and anthropogenic factors. Additionally, the seasonal types of lake water color were analyzed, with the west and east showing opposite patterns, reflecting the significant influence of topographic features and seasonal changes in climate on water color. The research results provide techniques for accurate inversion of FUI using MODIS-500 m data, while deepening the understanding of long-term water color changes in inland lakes in China.
ABSTRACT
Heparins have been invaluable therapeutic anticoagulant polysaccharides for over a century, whether used as unfractionated heparin or as low molecular weight heparin (LMWH) derivatives. However, heparin production by extraction from animal tissues presents multiple challenges, including the risk of adulteration, contamination, prion and viral impurities, limited supply, insecure supply chain, and significant batch-to-batch variability. The use of animal-derived heparin also raises ethical and religious concerns, as well as carries the risk of transmitting zoonotic diseases. Chemoenzymatic synthesis of animal-free heparin products would offer several advantages, including reliable and scalable production processes, improved purity and consistency, and the ability to produce heparin polysaccharides with molecular weight, structural, and functional properties equivalent to those of the United States Pharmacopeia (USP) heparin, currently only sourced from porcine intestinal mucosa. We report a scalable process for the production of bioengineered heparin that is biologically and compositionally similar to USP heparin. This process relies on enzymes from the heparin biosynthetic pathway, immobilized on an inert support and requires a tailored N-sulfoheparosan with N-sulfo levels similar to those of porcine heparins. We also report the conversion of our bioengineered heparin into a LMWH that is biologically and compositionally similar to USP enoxaparin. Ultimately, we demonstrate major advances to a process to provide a potential clinical and sustainable alternative to porcine-derived heparin products.
Subject(s)
Heparin, Low-Molecular-Weight , Heparin , Animals , Swine , Heparin/metabolism , Heparin, Low-Molecular-Weight/chemistry , Anticoagulants/chemistry , Molecular Weight , Drug ContaminationABSTRACT
Quantum ghost image technique utilizing position or momentum correlations between entangled photons can realize nonlocal reconstruction of the image of an object. In this work, based on polarization entanglement, we experimentally demonstrate quantum ghost imaging of vector images by using a geometric phase object. We also provide a corresponding theoretical analysis. Additionally, we offer a geometrical optics path explanation of ghost imaging for vector fields. The proposed strategy offers new insights into the fundamental development of ghost imaging and also holds great promise for developing complex structured ghost imaging techniques. Our work expanding the principle of ghost imaging to spatially varying vector beams will lead to interesting developments of this field.
ABSTRACT
Many Dendrobium species, which hold a high status and value in traditional Chinese medicine, grow on barks and rocks in the wild, often encountering harsh environments and facing droughts. However, the molecular mechanisms underlying the shift in the photosynthetic pathway induced by drought remain unclear. To address this issue, three Dendrobium species with different photosynthetic pathways were selected for sequencing and transcriptome data analysis after drought treatment. The findings included 134.43 GB of sequencing data, with numerous Differentially Expressed Genes (DEGs) exhibiting different response mechanisms under drought stress. Gene Ontology (GO)-KEGG-based enrichment analysis of DEGs revealed that metabolic pathways contributed to drought tolerance and alterations in photosynthetic pathways. Phosphoenolpyruvate Carboxylase (PEPC) was subjected to phylogenetic tree construction, sequence alignment, and domain analysis. Under drought stress, variations were observed in the PEPC gene structure and expression among different Dendrobium species; the upregulation of Dc_gene2609 expression may be caused by dof-miR-384, which resulted in the shift from C3 photosynthesis to CAM, thereby improving drought tolerance in Dendrobium. This study revealed the expression patterns and roles of PEPC genes in enhancing plant drought tolerance and will provide an important basis for in-depth research on Dendrobium's adaptation mechanisms in arid environments.
Subject(s)
Dendrobium , Droughts , Dendrobium/genetics , Phylogeny , Transcriptome , Gene Expression Profiling , Photosynthesis , Stress, Physiological/genetics , Gene Expression Regulation, PlantABSTRACT
Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus with high contagion and mortality rates. Heparan sulfate proteoglycans (HSPGs) are ubiquitously expressed on the surface of mammalian cells. Owing to its high negatively charged property, heparan sulfate (HS) on the surface of host cells is used by many viruses as cofactor to facilitate viral attachment and initiate cellular entry. Therefore, inhibition of the interaction between viruses and HS could be a promising target to inhibit viral infection. In the current study, the interaction between the receptor-binding domain (RBD) of MERS-CoV and heparin was exploited to assess the inhibitory activity of various sulfated glycans such as glycosaminoglycans, marine-sourced glycans (sulfated fucans, fucosylated chondroitin sulfates, fucoidans, and rhamnan sulfate), pentosan polysulfate, and mucopolysaccharide using Surface Plasmon Resonance. We believe this study provides valuable insights for the development of sulfated glycan-based inhibitors as potential antiviral agents.
Subject(s)
Heparin , Middle East Respiratory Syndrome Coronavirus , Animals , Heparin/pharmacology , Middle East Respiratory Syndrome Coronavirus/metabolism , Sulfates/chemistry , Glycosaminoglycans/metabolism , Heparitin Sulfate/metabolism , MammalsABSTRACT
BACKGROUND: Heart failure (HF) often disrupts the protein quality control (PQC) system leading to protein aggregate accumulation. Evidence from tissue biopsies showed that exercise restores PQC system in HF; however, little is known about its effects on plasma proteostasis. AIM: To determine the effects of exercise training on the load and composition of plasma SDS-resistant protein aggregates (SRA) in patients with HF with reduced ejection fraction (HFrEF). METHODS: Eighteen patients with HFrEF (age: 63.4 ± 6.5 years; LVEF: 33.4 ± 11.6%) participated in a 12-week combined (aerobic plus resistance) exercise program (60 min/session, twice per week). The load and content of circulating SRA were assessed using D2D SDS-PAGE and mass spectrometry. Cardiorespiratory fitness, quality of life, and circulating levels of high-sensitive C-reactive protein, N-terminal pro-B-type natriuretic peptide (NT-proBNP), haptoglobin and ficolin-3, were also evaluated at baseline and after the exercise program. RESULTS: The exercise program decreased the plasma SRA load (% SRA/total protein: 38.0 ± 8.9 to 36.1 ± 9.7%, p = 0.018; % SRA/soluble fraction: 64.3 ± 27.1 to 59.8 ± 27.7%, p = 0.003). Plasma SRA of HFrEF patients comprised 31 proteins, with α-2-macroglobulin and haptoglobin as the most abundant ones. The exercise training significantly increased haptoglobin plasma levels (1.03 ± 0.40 to 1.11 ± 0.46, p = 0.031), while decreasing its abundance in SRA (1.83 ± 0.54 × 1011 to 1.51 ± 0.59 × 1011, p = 0.049). Cardiorespiratory fitness [16.4(5.9) to 19.0(5.2) ml/kg/min, p = 0.002], quality of life, and circulating NT-proBNP [720.0(850.0) to 587.0(847.3) pg/mL, p = 0.048] levels, also improved after the exercise program. CONCLUSION: Exercise training reduced the plasma SRA load and enhanced PQC, potentially via haptoglobin-mediated action, while improving cardiorespiratory fitness and quality of life of patients with HFrEF.
ABSTRACT
Tuning transport properties through the manipulation of elementary structures has achieved great success in many areas, such as condensed matter physics. However, the ability to manipulate coherent structures in turbulent flows is much less explored. This article reviews a recently discovered mechanism of tuning turbulent heat transport via coherent structure manipulation. We first show how this mechanism can be realized by applying simple geometrical confinement to a classical thermally driven turbulence, which leads to the condensation of elementary coherent structures and significant heat-transport enhancement, despite the resultant slower flow. Some potential applications of this new paradigm in passive heat management are also discussed. We then explain how the heat transport behaviors in seemingly different turbulence systems can be understood by this unified framework of coherent structure manipulation. Several future directions in this research area are also outlined.
ABSTRACT
Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) and influenza viruses have spread around the world at an unprecedented rate. Despite multiple vaccines, new variants of SARS-CoV-2 and influenza have caused a remarkable level of pathogenesis. The development of effective antiviral drugs to treat SARS-CoV-2 and influenza remains a high priority. Inhibiting viral cell surface attachment represents an early and efficient means to block virus infection. Sialyl glycoconjugates, on the surface of human cell membranes, play an important role as host cell receptors for influenza A virus and 9-O-acetyl-sialylated glycoconjugates are receptors for MERS, HKU1 and bovine coronaviruses. We designed and synthesized multivalent 6'-sialyllactose-counjugated polyamidoamine dendrimers through click chemistry at room temperature concisely. These dendrimer derivatives have good solubility and stability in aqueous solutions. SPR, a real-time analysis quantitative method for of biomolecular interactions, was used to study the binding affinities of our dendrimer derivatives by utilizing only 200 micrograms of each dendrimer. Three SARS-CoV-2 S-protein receptor binding domain (wild type and two Omicron mutants) bound to multivalent 9-O-acetyl-6'-sialyllactose-counjugated and 6'-sialyllactose-counjugated dendrimers bound to a single H3N2 influenza A virus's HA protein (A/Hong Kong/1/1968), the SPR study results suggest their potential anti-viral activities.
Subject(s)
COVID-19 , Dendrimers , Influenza, Human , Animals , Cattle , Humans , Spike Glycoprotein, Coronavirus/chemistry , SARS-CoV-2/metabolism , Dendrimers/pharmacology , Dendrimers/metabolism , Influenza, Human/drug therapy , Hemagglutinins , Influenza A Virus, H3N2 Subtype/metabolism , Antiviral Agents/chemistry , Protein BindingABSTRACT
Decellularized lung scaffolds and hydrogels are increasingly being utilized in ex vivo lung bioengineering. However, the lung is a regionally heterogenous organ with proximal and distal airway and vascular compartments of different structures and functions that may be altered as part of disease pathogenesis. We previously described decellularized normal whole human lung extracellular matrix (ECM) glycosaminoglycan (GAG) composition and functional ability to bind matrix-associated growth factors. We now determine differential GAG composition and function in airway, vascular, and alveolar-enriched regions of decellularized lungs obtained from normal, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF) patients. Significant differences were observed in heparan sulfate (HS), chondroitin sulfate (CS), and hyaluronic acid (HA) content and CS/HS compositions between both different lung regions and between normal and diseased lungs. Surface plasmon resonance demonstrated that HS and CS from decellularized normal and COPD lungs similarly bound fibroblast growth factor 2, but that binding was decreased in decellularized IPF lungs. Binding of transforming growth factor ß to CS was similar in all three groups but binding to HS was decreased in IPF compared to normal and COPD lungs. In addition, cytokines dissociate faster from the IPF GAGs than their counterparts. The differences in cytokine binding features of IPF GAGs may result from different disaccharide compositions. The purified HS from IPF lung is less sulfated than that from other lungs, and the CS from IPF contains more 6-O-sulfated disaccharide. These observations provide further information for understanding functional roles of ECM GAGs in lung function and disease. STATEMENT OF SIGNIFICANCE: Lung transplantation remains limited due to donor organ availability and need for life-long immunosuppressive medication. One solution, the ex vivo bioengineering of lungs via de- and recellularization has not yet led to a fully functional organ. Notably, the role of glycosaminoglycans (GAGs) remaining in decellularized lung scaffolds is poorly understood despite their important effects on cell behaviors. We have previously investigated residual GAG content of native and decellularized lungs and their respective functionality, and role during scaffold recellularization. We now present a detailed characterization of GAG and GAG chain content and function in different anatomical regions of normal diseased human lungs. These are novel and important observations that further expand knowledge about functional GAG roles in lung biology and disease.
Subject(s)
Glycosaminoglycans , Pulmonary Disease, Chronic Obstructive , Humans , Glycosaminoglycans/metabolism , Lung/pathology , Chondroitin Sulfates , Pulmonary Disease, Chronic Obstructive/metabolism , Pulmonary Disease, Chronic Obstructive/pathology , Extracellular Matrix/metabolism , Disaccharides/analysis , Disaccharides/metabolismABSTRACT
Psilocybin, a naturally occurring hallucinogenic component of magic mushrooms, has significant psychoactive effects in both humans and rodents. But the underlying mechanisms are not fully understood. Blood-oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is a useful tool in many preclinical and clinical trials to investigate psilocybin-induced changes of brain activity and functional connectivity (FC) due to its noninvasive nature and widespread availability. However, fMRI effects of psilocybin on rats have not been carefully investigated. This study aimed to explore how psilocybin affects resting-state brain activity and FC, through a combination of BOLD fMRI and immunofluorescence (IF) of EGR1, an immediate early gene (IEG) closely related to depressive symptoms. Ten minutes after psilocybin hydrochloride injection (2.0 mg/kg, i.p.), positive brain activities were observed in the frontal, temporal, and parietal cortex (including the cingulate cortex and retrosplenial cortex), hippocampus, and striatum. And a region-of-interest (ROI) -wise FC analysis matrix suggested increased interconnectivity of several regions, such as the cingulate cortex, dorsal striatum, prelimbic, and limbic regions. Further seed-based analyses revealed increased FC of cingulate cortex within the cortical and striatal areas. Consistently, acute psilocybin increased the EGR1 level throughout the brain, indicating a consistent activation thought the cortical and striatal areas. In conclusion, the psilocybin-induced hyperactive state of rats is congruent to that of humans, and may be responsible for its pharmacological effects.
ABSTRACT
We present an experimental study of the velocity circulation in a quasi-two-dimensional turbulent flow. We show that the area rule of circulation around simple loops holds in both the forward cascade enstrophy inertial range (ΩIR) and the inverse cascade energy inertial range (EIR): When the side lengths of a loop are all within the same inertial range, the circulation statistics depend on the loop area alone. It is also found that, for circulation around figure-eight loops, the area rule still holds in EIR but is not applicable in ΩIR. In ΩIR, the circulation is nonintermittent; whereas in EIR, the circulation is bifractal: space filling for moments of the order of 3 and below and a monofractal with a dimension of 1.42 for higher orders. Our results demonstrate, as in a numerical study of 3D turbulence [K. P. Iyer et al., Circulation in High Reynolds Number Isotropic Turbulence is a Bifractal, Phys. Rev. X 9, 041006 (2019).PRXHAE2160-330810.1103/PhysRevX.9.041006], that, in terms of circulation, turbulent flows exhibit a simpler behavior than velocity increments, as the latter are multifractals.
ABSTRACT
Sulfated glycans from marine organisms are excellent sources of naturally occurring glycosaminoglycan (GAG) mimetics that demonstrate therapeutic activities, such as antiviral/microbial infection, anticoagulant, anticancer, and anti-inflammation activities. Many viruses use the heparan sulfate (HS) GAG on the surface of host cells as co-receptors for attachment and initiating cell entry. Therefore, virion-HS interactions have been targeted to develop broad-spectrum antiviral therapeutics. Here we report the potential anti-monkeypox virus (MPXV) activities of eight defined marine sulfated glycans, three fucosylated chondroitin sulfates, and three sulfated fucans extracted from the sea cucumber species Isostichopus badionotus, Holothuria floridana, and Pentacta pygmaea, and the sea urchin Lytechinus variegatus, as well as two chemically desulfated derivatives. The inhibitions of these marine sulfated glycans on MPXV A29 and A35 protein-heparin interactions were evaluated using surface plasmon resonance (SPR). These results demonstrated that the viral surface proteins of MPXV A29 and A35 bound to heparin, which is a highly sulfated HS, and sulfated glycans from sea cucumbers showed strong inhibition of MPXV A29 and A35 interactions. The study of molecular interactions between viral proteins and host cell GAGs is important in developing therapeutics for the prevention and treatment of MPXV.
Subject(s)
Glycosaminoglycans , Sea Cucumbers , Animals , Glycosaminoglycans/chemistry , Surface Plasmon Resonance , Sulfates/pharmacology , Sulfates/chemistry , Heparitin Sulfate/pharmacology , Chondroitin Sulfates , Heparin/pharmacology , Sea Cucumbers/chemistry , Antiviral Agents/pharmacologyABSTRACT
Chronic inflammation and dyslipidemia are important risk factors in developing atherosclerotic cardiovascular disease, such as coronary heart disease. Acute coronary syndrome (ACS) is one of the most dangerous syndromes in coronary heart disease. Type 2 diabetes mellitus (T2DM) is considered equal to coronary heart disease owing to the high cardiac risk induced by chronic inflammation and dyslipidemia. The neutrophil to high-density lipoprotein cholesterol ratio (NHR) is a novel and straightforward marker that reflects inflammation and lipid metabolic disorder. However, few studies have been on the role of NHR in assessing the risk of ACS in T2DM patients. Here we analyzed NHR level in ACS patients with T2DM, exploring its predictive and diagnostic values. 211 hospitalized ACS patients with T2DM were recruited as the case group, and 168 hospitalized T2DM patients as the control group (all patients collected from 6/2020 to 12/2021 in Xiangya Hospital). Biochemical test results and echocardiograms, as well as demographic information such as age, BMI, diabetes mellitus, smoking, drinking, and history of hypertension, were recorded. Frequencies, percentages, means, and standard deviations were used to describe the data. The shapiro-Wilk test was used to assess the normality of the data. Normally distributed data were compared using the independent sample T-test, and non-normally distributed data were compared using Mann-Whitney U test. Correlation analysis was performed using the Spearman rank correlation test, and receiver operating characteristic (ROC) curve analysis and multivariable logistic regression analysis were performed by SPSS version 24.0 (SPSS Inc) and GraphPad Prism 9.0 (GraphPad Software Inc). p < 0.05 was considered significant. In the study population, NHR was higher in patients with T2DM combined with ACS than in T2DM patients without ACS (p < 0.001). After adjusting for BMI, alcohol consumption, and history of hypertension, multifactorial logistic regression analysis revealed that NHR is a risk factor for T2DM patients combined with ACS (OR 1.221, p = 0.0126). Correlation analysis on all ACS patients with T2DM showed that NHR level was positively correlated with cTnI (r = 0.437, p < 0.001), CK (r = 0.258, p = 0.001), CK-Mb (r = 0.447, p < 0.001), LDH (r = 384, p < 0.001), Mb (r = 0.320, p < 0.001), LA (r = 0.168, p = 0.042) and LV levels (r = 0.283, p = 0.001). And meanwhile, NHR level was negatively correlated with EF (r = - 0.327, p < 0.001) and FS levels (r = - 0.347, p < 0.001). ROC curve analysis showed that NHR ⧠4.32 had a sensitivity of 65.45% and a specificity of 66.19% for predicting ACS in T2DM patients [area under the curve (AUC) = 0.722, p < 0.001]. Furthermore, in all ACS patients with T2DM, the diagnostic power of NHR was stronger in ST-segment elevated ACS patients (STE-ACS) than that in non-ST-segment elevated ACS patients (NSTE-ACS) (p < 0.001). With its convenience and effective character, NHR could be a potential and new marker for predicting the presence, progression, and severity of ACS in T2DM population.
Subject(s)
Acute Coronary Syndrome , Coronary Disease , Diabetes Mellitus, Type 2 , Hypertension , Humans , Acute Coronary Syndrome/diagnosis , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Cross-Sectional Studies , Cholesterol, HDL , Neutrophils , Coronary Disease/complications , Inflammation/complications , Hypertension/complicationsABSTRACT
Heparin is a commonly used anticoagulant drug, derived from the tissues of animals including pigs, cows, and sheep. Measuring heparin concentration in plasma is challenging due to its complex molecular structure. Existing methods rely on measuring heparin's anticoagulant activity, which provides pharmacodynamic (PD) data but not pharmacokinetic (PK) data, measuring concentration over time. To overcome this limitation, we used liquid chromatography-mass spectrometry (LC-MS) and the multiple reaction monitoring (MRM) method to directly measure heparin's concentration in non-human primates after administering porcine, bovine, and ovine heparin. A protocol was developed to enable an MRM method for application to small plasma volumes without purification. The PK data obtained from LC-MS are then compared with the data obtained using the Heparin Red assay and the PD data determined using biochemical clinical assays. Results showed that LC-MS and Heparin Red assay measurements closely correlated with unfractionated heparin's biological activities, supporting the use of mass spectra and dye-binding assays to determine heparin levels in plasma. This study builds a way for the measurement of heparin concentration in plasma, which could lead to an improved understanding of heparin's metabolism and dosing safety.
Subject(s)
Anticoagulants , Heparin , Female , Animals , Cattle , Sheep , Swine , Heparin/chemistry , Anticoagulants/pharmacology , Anticoagulants/chemistry , Primates/metabolism , Chromatography, Liquid , Mass SpectrometryABSTRACT
Heparan sulfate (HS) is a heterogeneous, cell-surface polysaccharide critical for transducing signals essential for mammalian development. Imaging of signaling proteins has revealed how their localization influences their information transfer. In contrast, the contribution of the spatial distribution and nanostructure of information-rich, signaling polysaccharides like HS is not known. Using expansion microscopy (ExM), we found striking changes in HS nanostructure occur as human pluripotent stem (hPS) cells differentiate, and these changes correlate with growth factor signaling. Our imaging studies show that undifferentiated hPS cells are densely coated with HS displayed as hair-like protrusions. This ultrastructure can recruit fibroblast growth factor for signaling. When the hPS cells differentiate into the ectoderm lineage, HS is localized into dispersed puncta. This striking change in HS distribution coincides with a decrease in fibroblast growth factor binding to neural cells. While developmental variations in HS sequence were thought to be the primary driver of alterations in HS-mediated growth factor signaling, our high-resolution images indicate a role for the HS nanostructure. Our study highlights the utility of high-resolution glycan imaging using ExM. In the case of HS, we found that changes in how the polysaccharide is displayed link to profound differences in growth factor binding.
Subject(s)
Heparitin Sulfate , Pluripotent Stem Cells , Animals , Humans , Heparitin Sulfate/chemistry , Heparitin Sulfate/metabolism , Cell Differentiation , Pluripotent Stem Cells/metabolism , Signal Transduction , Fibroblast Growth Factors , Mammals/metabolismABSTRACT
Since the discovery of graphene in an atomic thin layer format, many investigations have been conducted to search for two-dimensional (2D) layered materials, in which 3d-transition metals offer much new physics and great freedom of tunability. In this work, through electron-beam irradiation, we enable the manufacture of a new 2D Ti nanosheet from a suspension of Ti0.91O2 nanosheets. In state-of-the-art density functional theory (DFT), both empirical and linear response theory predicted that Hubbard Ueff values would be imposed, resulting in unstable phonon dispersion curves. In the end, the newly found Ti monolayer is confirmed to be a non-magnetic superconductor, with a medium level of electron-phonon coupling. The newly established Ti layer is quite robust under strain, and the evolution of local Dirac points in electronic bands is also analyzed in terms of linearity and energetic shift near the Fermi energy. As suggested by the Fermi surface, this metal monolayer experiences an electronic topological transition under strain. Our findings will encourage many more explorations of pure d metal-based isotopic monolayers with diverse structures and open a new playground for 2D superconductors and ultra-thin sensoring components.