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π-Stacking, a type of noncovalent interactions involving aromatic residues, plays an important role in protein folding and function. In this work, an attempt has been made to measure CH/π and NH/π stacking interactions in a protein in Escherichia coli cells using a combined double-mutant cycle and nuclear magnetic resonance spectroscopy method. The results show that the CH/π and NH/π stacking interactions are generally weaker in cells than those in the buffer. The transient intermolecular noncovalent interactions between the protein and the complex cellular environment may compete with and thus weaken the stacking interactions in the protein. The weakening of stacking interactions can enhance the local conformational opening of proteins in E. coli cells. This is evident from the faster rates of amide hydrogen/deuterium exchange observed in cells than in the buffer, for residues that undergo local conformational opening. This study highlights the influence of the cellular environment on π-stacking and the conformational dynamics of proteins.
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OBJECTIVES: To explore the association between tea, coffee, and caffeine consumption and the risk of female infertility. METHODS: We analyzed data from 2099 females aged 18 to 44 years, participating in the National Health and Nutrition Examination Survey (NHANES) 2013-2018. We used generalized linear models (GLM) and generalized additive model (GAM) to investigate the dose-response relationship between the tea, coffee, and caffeine consumption and infertility, adjusting for potential confounders. RESULTS: A non-linear relationship was detected between tea consumption and infertility and the inflection point was 2 cups/day. On the right side of the inflection point, we did not detect a significant association. However, on the left side, we found a negative relationship between tea consumption and infertility (OR: 0.73; 95% CI: 0.57 to 0.93; P = 0.0122). Meanwhile, our study found no significant association between coffee (0.96, 0.81 to 1.13, P = 0.6189) or caffeine consumption (1.15, 0.93 to 1.42, P = 0.2148) and female infertility. CONCLUSIONS: Tea consumption was non-linearly associated with infertility, whereas no significant associations were found between coffee, caffeine consumption and infertility.
Subject(s)
Caffeine , Coffee , Infertility, Female , Tea , Humans , Female , Tea/adverse effects , Coffee/adverse effects , Caffeine/adverse effects , Caffeine/administration & dosage , Adult , Cross-Sectional Studies , Infertility, Female/epidemiology , Young Adult , Adolescent , Nutrition Surveys , Risk FactorsABSTRACT
Posttraumatic stress disorder (PTSD) is a complex mental disorder notable for traumatic experience memory. Although current first-line treatments are linked with clinically important symptom reduction, a large proportion of patients retained to experience considerable residual symptoms, indicating pathogenic mechanism should be illustrated further. Recent studies reported that newly formed myelin could shape neural circuit function and be implicated in fear memory preservation. However, its role in PTSD remains to be elucidated. In this study, we adopted a restraint stress-induced PTSD mouse model and found that PTSD-related neuropsychiatric symptoms were accompanied by increased myelination in the posterior parietal cortex and hippocampus. Fluoxetine, but not risperidone or sertraline, has a more profound rescue effect on neuropsychological behaviors and myelin abnormalities. Further mechanistic experiments revealed that fluoxetine could directly interfere with oligodendroglial differentiation by upregulating Wnt signaling. Our data demonstrated the correlation between PTSD and abnormal myelination, suggesting that the oligodendroglial lineage could be a target for PTSD treatment.
Subject(s)
Disease Models, Animal , Fluoxetine , Mice, Inbred C57BL , Myelin Sheath , Stress Disorders, Post-Traumatic , Animals , Stress Disorders, Post-Traumatic/drug therapy , Fluoxetine/pharmacology , Fluoxetine/therapeutic use , Myelin Sheath/drug effects , Myelin Sheath/pathology , Myelin Sheath/metabolism , Male , Mice , Hippocampus/drug effects , Hippocampus/metabolism , Oligodendroglia/drug effects , Oligodendroglia/metabolism , Parietal Lobe/drug effects , Wnt Signaling Pathway/drug effects , Selective Serotonin Reuptake Inhibitors/pharmacologyABSTRACT
Objective: To evaluate the association between bedtime and infertility and to identify the optimal bedtime for women of reproductive age. Methods: We conducted a cross-sectional study using data from 3,903 female participants in the National Health and Nutrition Examination Survey (NHANES) from 2015 to 2020. The effect of bedtime on female infertility was assessed using the binary logistic regression in different models, including crude model and adjusted models. To identify the non-linear correlation between bedtime and infertility, generalized additive models (GAM) were utilized. Subgroup analyses were conducted by age, body mass index (BMI), waist circumference, physical activity total time, marital status, smoking status, drinking status and sleep duration. Results: After adjusting for potential confounders (age, race, sleep duration, waist circumference, marital status, education, BMI, smoking status, drinking status and physical activity total time), a non-linear relationship was observed between bedtime and infertility, with the inflection point at 22:45. To the left side of the inflection point, no significant association was detected. However, to the right of it, bedtime was positively related to the infertility (OR: 1.22; 95% CI: 1.06 to 1.39; P = 0.0049). Subgroup analyses showed that late sleepers with higher BMI were more prone to infertility than those with a lower BMI (BMI: 25-30 kg/m2: OR: 1.26; 95% CI: 1.06 to 1.51; P = 0.0136; BMI ≥ 30 kg/m²: OR: 1.21, 95% CI: 1.09 to 1.34; P = 0.0014). Conclusion: Bedtime was non-linearly associated with infertility, which may provide guidance for sleep behavior in women of childbearing age.
Subject(s)
Body Mass Index , Infertility, Female , Nutrition Surveys , Sleep , Humans , Female , Cross-Sectional Studies , Adult , Infertility, Female/epidemiology , Sleep/physiology , Exercise , Young Adult , Middle Aged , Waist Circumference/physiology , Time FactorsABSTRACT
Background: Organophosphorus compounds, widely used in agriculture and industry, pose a serious threat to human health due to their acute neurotoxicity. Although traditional interventions for organophosphate poisoning are effective, they often come with significant side effects. Objective: This paper aims to evaluate the potential of enzymes within biological organisms as organophosphorus bioclearing agents. It analyses the technical challenges in current enzyme research, such as substrate specificity, stereoselectivity, and immunogenicity, while exploring recent advancements in the field. Methods: A comprehensive review of literature related to detoxifying enzymes or proteins was conducted. Existing studies on organophosphorus bioclearing agents were summarised, elucidating the biological detoxification mechanisms, with a particular focus on advancements in protein engineering and novel delivery methods. Results: Current bioclearing agents can be categorised into stoichiometric and catalytic bioclearing agents, both of which have shown some success in preventing organophosphate poisoning. Technological advancements have significantly improved various properties of bioclearing agents, yet challenges remain, particularly in substrate specificity, stereoselectivity, and immunogenicity. Future research will focus on expanding the substrate spectrum, enhancing catalytic efficiency, prolonging in vivo half-life, and developing convenient administration methods. Conclusion: With the progression of clinical trials, bioclearing agents are expected to become widely used as a new generation of therapeutic organophosphate detoxifiers.
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OBJECTIVES: To explore the relationship between different types of physical activity and female infertility. METHODS: This study analyzed data from 2,796 female participants aged 18-44 years in the United States, obtained from the National Health and Nutrition Examination Survey (NHANES) database spanning the years 2013 to 2020. Multiple logistic regression analyses and generalized linear models were used to explore the relationship between different types of physical activity and infertility after adjusting for potential confounding factors. RESULTS: We found a non-linear relationship between recreational activities and infertility with an inflection point of 5.83 h/week (moderate intensity), while work activities and traffic-related activities did not. On the left side of the inflection point, there was no significant association between recreational activity time and infertility (OR = 0.93, 95% CI: 0.86 to 1.02, P = 0.1146), but on the right side of the inflection point, there was a positive association between recreational activity time and the risk of infertility (OR = 1.04, 95% CI: 1.02 to 1.06, P = 0.0008). CONCLUSIONS: The relationship between different types of physical activity and female infertility varies. We acknowledge the potential influence of confounding variables on this relationship. However, we have already adjusted for these potential variables in our analysis. Therefore, our findings suggest that appropriate recreational activity programs are essential for promoting reproductive health in women of reproductive age. Nevertheless, it is important to note that the observed association does not imply causality. Given the limitations of cross-sectional studies, further prospective cohort studies are needed to explore the causal relationship while accounting for additional confounding factors.
Subject(s)
Exercise , Infertility, Female , Nutrition Surveys , Humans , Female , Adult , Infertility, Female/epidemiology , Infertility, Female/etiology , Exercise/physiology , Young Adult , Adolescent , United States/epidemiology , Cross-Sectional StudiesABSTRACT
White matter injury (WMI) causes oligodendrocyte precursor cell (OPC) differentiation arrest and functional deficits, with no effective therapies to date. Here, we report increased expression of growth hormone (GH) in the hypoxic neonatal mouse brain, a model of WMI. GH treatment during or post hypoxic exposure rescues hypoxia-induced hypomyelination and promotes functional recovery in adolescent mice. Single-cell sequencing reveals that Ghr mRNA expression is highly enriched in vascular cells. Cell-lineage labeling and tracing identify the GHR-expressing vascular cells as a subpopulation of pericytes. These cells display tip-cell-like morphology with kinetic polarized filopodia revealed by two-photon live imaging and seemingly direct blood vessel branching and bridging. Gain-of-function and loss-of-function experiments indicate that GHR signaling in pericytes is sufficient to modulate angiogenesis in neonatal brains, which enhances OPC differentiation and myelination indirectly. These findings demonstrate that targeting GHR and/or downstream effectors may represent a promising therapeutic strategy for WMI.
Subject(s)
Myelin Sheath , Neovascularization, Physiologic , Pericytes , Animals , Pericytes/metabolism , Pericytes/drug effects , Mice , Myelin Sheath/metabolism , Neovascularization, Physiologic/drug effects , Neovascularization, Physiologic/physiology , Growth Hormone/metabolism , Growth Hormone/pharmacology , Animals, Newborn , Hypoxia/metabolism , Cell Differentiation/drug effects , Mice, Inbred C57BL , Oligodendrocyte Precursor Cells/metabolism , Oligodendrocyte Precursor Cells/drug effects , Receptors, Somatotropin/metabolism , Receptors, Somatotropin/genetics , AngiogenesisABSTRACT
Protein allostery is commonly observed in vitro. But how protein allostery behaves in cells is unknown. In this work, a protein monomer-dimer equilibrium system was built with the allosteric effect on the binding characterized using NMR spectroscopy through mutations away from the dimer interface. A chemical shift linear fitting method was developed that enabled us to accurately determine the dissociation constant. A total of 28 allosteric mutations were prepared and grouped to negative allosteric, nonallosteric, and positive allosteric modulators. â¼ 50% of mutations displayed the allosteric-state changes when moving from a buffered solution into cells. For example, there were no positive allosteric modulators in the buffered solution but eight in cells. The change in protein allostery is correlated with the interactions between the protein and the cellular environment. These interactions presumably drive the surrounding macromolecules in cells to transiently bind to the monomer and dimer mutational sites and change the free energies of the two species differently which generate new allosteric effects. These surrounding macromolecules create a new protein allostery pathway that is only present in cells.
Subject(s)
Nuclear Magnetic Resonance, Biomolecular , Allosteric Regulation , Mutation , Protein Multimerization , Models, MolecularABSTRACT
BACKGROUND AND AIMS: Current research has suggested that asialoglycoprotein receptor 1 (ASGR1) is involved in cholesterol metabolism and is also related to systemic inflammation. This study aimed to assess the correlation between the serum soluble ASGR1 (sASGR1) concentration and inflammatory marker levels. Moreover, the second objective of the study was to assess the association between sASGR1 levels and the presence of coronary artery disease (CAD). METHODS: The study subjects included 160 patients who underwent coronary angiography. Ninety patients were diagnosed with CAD, while seventy age- and sex-matched non-CAD patients served as controls. We measured the serum sASGR1 levels using an ELISA kit after collecting clinical baseline characteristics. RESULTS: Patients with CAD had higher serum sASGR1 levels than non-CAD patients did (P < 0.0001). sASGR1 was independently correlated with the risk of CAD after adjusting for confounding variables (OR = 1.522, P = 0.012). The receiver operating characteristic (ROC) curve showed that sASGR1 had a larger area under the curve (AUC) than did the conventional biomarkers apolipoprotein B (APO-B) and low-density lipoprotein cholesterol (LDL-C). In addition, multivariate linear regression models revealed that sASGR1 is independently and positively correlated with high-sensitivity C-reactive protein (CRP) (ß = 0.86, P < 0.001) and WBC (ß = 0.13, P = 0.004) counts even after adjusting for lipid parameters. According to our subgroup analysis, this relationship existed only for CAD patients. CONCLUSION: Our research demonstrated the link between CAD and sASGR1 levels, suggesting that sASGR1 may be an independent risk factor for CAD. In addition, this study provides a reference for revealing the potential role of sASGR1 in the inflammation of atherosclerosis.
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Coronary Artery Disease , Humans , Coronary Angiography/adverse effects , Risk Factors , Biomarkers , Inflammation/complications , Cholesterol , Asialoglycoprotein ReceptorABSTRACT
BACKGROUND: Tumor angiogenesis inhibitors have been applied for non-small cell lung cancer (NSCLC) therapy. However, the drug resistance hinders their further development. Intercellular crosstalk between lung cancer cells and vascular cells was crucial for anti-angiogenenic resistance (AAD). However, the understanding of this crosstalk is still rudimentary. Our previous study showed that Glioma-associated oncogene 1 (Gli1) is a driver of NSCLC metastasis, but its role in lung cancer cell-vascular cell crosstalk remains unclear. METHODS: Conditioned medium (CM) from Gli1-overexpressing or Gli1-knockdown NSCLC cells was used to educate endothelia cells and pericytes, and the effects of these media on angiogenesis and the maturation of new blood vessels were evaluated via wound healing assays, Transwell migration and invasion assays, tube formation assays and 3D coculture assays. The xenograft model was conducted to establish the effect of Gli1 on tumor angiogenesis and growth. Angiogenic antibody microarray analysis, ELISA, luciferase reporte, chromatin immunoprecipitation (ChIP), bFGF protein stability and ubiquitination assay were performed to explore how Gli1 regulate bFGF expression. RESULTS: Gli1 overexpression in NSCLC cells enhanced the endothelial cell and pericyte motility required for angiogenesis required for angiogenesis. However, Gli1 knockout in NSCLC cells had opposite effect on this process. bFGF was critical for the enhancement effect on tumor angiogenesis. bFGF treatment reversed the Gli1 knockdown-mediated inhibition of angiogenesis. Mechanistically, Gli1 increased the bFGF protein level by promoting bFGF transcriptional activity and protein stability. Importantly, suppressing Gli1 with GANT-61 obviously inhibited angiogenesis. CONCLUSION: The Gli1-bFGF axis is crucial for the crosstalk between lung cancer cells and vascular cells. Targeting Gli1 is a potential therapeutic approach for NSCLC angiogenesis.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/metabolism , Lung Neoplasms/metabolism , Pericytes/metabolism , Pericytes/pathology , Zinc Finger Protein GLI1/genetics , Zinc Finger Protein GLI1/metabolism , Angiogenesis , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/pathology , Cell Movement , Cell Line, Tumor , Cell ProliferationABSTRACT
Reducing circulating lipid levels is the centerpiece of strategies for preventing and treating atherosclerotic cardiovascular disease (ASCVD). Despite many available lipid-lowering medications, a substantial residual cardiovascular risk remains. Current clinical guidelines focus on plasma levels of low-density lipoprotein (LDL). Recent attention has been given to very low-density lipoprotein (VLDL), the precursor to LDL, and its role in the development of coronary atherosclerosis. Preclinical investigations have revealed that interventions targeting VLDL production or promoting VLDL metabolism, independent of the LDL receptor, can potentially decrease cholesterol levels and provide therapeutic benefits. Currently, methods, such as mipomersen, lomitapide, and ANGPTL3 inhibitors, are used to reduce plasma cholesterol and triglyceride levels by regulating the lipidation, secretion, and metabolism of VLDL. Targeting VLDL represents an avenue for new lipid-lowering strategies. Interventions aimed at reducing VLDL production or enhancing VLDL metabolism, independent of the LDL receptor, hold promise for lowering cholesterol levels and providing therapeutic benefits beyond LDL in the management of ASCVD.
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Atherosclerosis , Lipoproteins, VLDL , Humans , Lipoproteins, LDL , Receptors, LDL/genetics , Cholesterol , Angiopoietin-Like Protein 3ABSTRACT
Ischaemic stroke causes neuron loss and long-term functional deficits. Unfortunately, effective approaches to preserving neurons and promoting functional recovery remain unavailable. Oligodendrocytes, the myelinating cells in the CNS, are susceptible to oxygen and nutrition deprivation and undergo degeneration after ischaemic stroke. Technically, new oligodendrocytes and myelin can be generated by the differentiation of oligodendrocyte precursor cells (OPCs). However, myelin dynamics and their functional significance after ischaemic stroke remain poorly understood. Here, we report numerous denuded axons accompanied by decreased neuron density in sections from ischaemic stroke lesions in human brain, suggesting that neuron loss correlates with myelin deficits in these lesions. To investigate the longitudinal changes in myelin dynamics after stroke, we labelled and traced pre-existing and newly-formed myelin, respectively, using cell-specific genetic approaches. Our results indicated massive oligodendrocyte death and myelin loss 2â weeks after stroke in the transient middle cerebral artery occlusion (tMCAO) mouse model. In contrast, myelin regeneration remained insufficient 4 and 8â weeks post-stroke. Notably, neuronal loss and functional impairments worsened in aged brains, and new myelin generation was diminished. To analyse the causal relationship between remyelination and neuron survival, we manipulated myelinogenesis by conditional deletion of Olig2 (a positive regulator) or muscarinic receptor 1 (M1R, a negative regulator) in OPCs. Deleting Olig2 inhibited remyelination, reducing neuron survival and functional recovery after tMCAO. Conversely, enhancing remyelination by M1R conditional knockout or treatment with the pro-myelination drug clemastine after tMCAO preserved white matter integrity and neuronal survival, accelerating functional recovery. Together, our findings demonstrate that enhancing myelinogenesis is a promising strategy to preserve neurons and promote functional recovery after ischaemic stroke.
Subject(s)
Brain Ischemia , Ischemic Stroke , Stroke , Mice , Animals , Humans , Aged , Myelin Sheath/pathology , Brain Ischemia/complications , Brain Ischemia/pathology , Stroke/complications , Stroke/pathology , Oligodendroglia/pathology , Neurons , Cell Differentiation/physiologyABSTRACT
Physical activity (PA) has the potential to bring about favourable changes in plasma lipid profile. However, the relationship between PA and remnant cholesterol (RC) remains unclear. We aimed to study the link between PA and RC using the database of the 2007-2020 National Health and Nutrition Examination Survey (NHANES). PA was categorized based on Physical Activity Guidelines for Americans. A multivariate linear regression model was used to determine the correlations between PA and RC. The study involved a total of 18,396 participants and revealed that individuals whose PA met the guidelines by engaging in moderate-intensity PA at least 150 min per week had lower body mass index and showed decreased levels of triglyceride, TC, and haemoglobin A1c compared to those who were physically inactive, exercising <150 min per week. Participants whose intensity of PA meets PA guidelines had a lower level of RC than those who did not met PA guidelines (ß = -1.3, 95% confidence interval [CI]: -1.9 to -0.7, p < 0.001), even after adjusting for confounders. During subgroup analysis, we observed that race (pinteraction = 0.0089) emerged as a significant factor of interaction.
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Cholesterol , Exercise , Humans , United States , Nutrition Surveys , Body Mass Index , Weight LossABSTRACT
BACKGROUND: Recent studies have shown that loss-of-function mutations in hepatic asialoglycoprotein receptor 1 (ASGR1) are associated with low levels of circulating cholesterol and a reduced risk of coronary artery disease (CAD). In contrast to ASGR1 on the hepatocyte membrane, serum soluble ASGR1 (sASGR1) is a secreted form that has been detected in circulation. However, the functions of serum sASGR1 are unclear. This study aims to investigate the relationship between human serum sASGR1 concentration and low-density lipoprotein cholesterol (LDL-C) levels. METHODS: In a cohort of 134 participants who underwent coronary angiography examination, basic information was recorded, and blood samples were collected for biochemical testing. The serum sASGR1 concentration was determined by ELISA kits. The relationship between sASGR1 concentration and LDL-C levels was examined using linear regression models and interaction tests. Univariate and multivariate analyses were used to identify clinical variables that affect sASGR1 levels. RESULTS: After adjusting for potential confounders such as age, sex, BMI, and statin use, the serum sASGR1 concentration was positively correlated with LDL-C levels (ß = 0.093, 95% CI: 0.04 to 0.14, P < 0.001). Subgroup analysis and interaction tests showed that the effect of serum sASGR1 concentration on LDL-C levels was significantly influenced by hypertension status (P for interaction = 0.0067). The results of a multivariate linear regression analysis incorporating age, serum TG, LDL-C, nonesterified fatty acid (NEFA), white blood cell counts (WBCC), and fibrinogen revealed that LDL-C (ß = 1.005, 95% CI: 0.35 to 1.66, P = 0.003) and WBCC (ß = 0.787, 95% CI: 0.41 to 1.16, P < 0.0001) were independent influencing factors for serum sASGR1 levels. CONCLUSIONS: The serum sASGR1 concentration was positively correlated with LDL-C levels. In addition, hypertension status significantly affected the effect of serum sASGR1 on LDL-C levels. This study provides some research ideas for clinical doctors and researchers, as well as some references for additional research on serum sASGR1.
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Hypertension , Humans , Cross-Sectional Studies , Cholesterol, LDL , Biological Transport , Coronary Angiography , Hypertension/genetics , Asialoglycoprotein ReceptorABSTRACT
Conformational dynamics is important for protein functions, many of which are performed in cells. How the intracellular environment may affect protein conformational dynamics is largely unknown. Here, loop conformational dynamics is studied for a model protein in Escherichia coli cells by using nuclear magnetic resonance (NMR) spectroscopy. The weak interactions between the protein and surrounding macromolecules in cells hinder the protein rotational diffusion, which extends the dynamic detection timescale up to microseconds by the NMR spin relaxation method. The loop picosecond to microsecond dynamics is confirmed by nanoparticle-assisted spin relaxation and residual dipolar coupling methods. The loop interactions with the intracellular environment are perturbed through point mutation of the loop sequence. For the sequence of the protein that interacts stronger with surrounding macromolecules, the loop becomes more rigid in cells. In contrast, the mutational effect on the loop dynamics in vitro is small. This study provides direct evidence that the intracellular environment can modify protein loop conformational dynamics through weak interactions.
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Escherichia coli , Proteins , Protein Conformation , Proteins/metabolism , Magnetic Resonance Spectroscopy , Mutation , Escherichia coli/genetics , Escherichia coli/metabolismABSTRACT
BACKGROUND: Protective antigen (PA) is an important biomarker for the early diagnosis of anthrax, and the accurate detection of protective antigen under extremely low concentration conditions has always been a hot topic in the biomedical field. To complete the diagnosis of anthrax in a timely manner, it is necessary to detect PA at extremely low concentrations, as the amount of PA produced in the early stage of anthrax invasion is relatively small. Graphene field-effect transistor (Gr-FET) biosensors are a new type of material for preparing biosensors, with the advantages of a short detection time and ultra-low detection limit. METHODS: The effect of different concentrations of diluents on the affinity of PA monoclonal antibodies was determined via an ELISA experiment. Combined with the Debye equation, 0.01 × PBS solution was finally selected as the diluent for the experiment. Then, a PA monoclonal antibody was selected as the bio-recognition element to construct a Gr-FET device based on CVD-grown graphene, which was used to detect the concentration of PA while recording the response time, linear range, detection limit, and other parameters. RESULTS: The experimental results showed that the biosensor could quickly detect PA, with a linear range of 10 fg/mL to 100 pg/mL and a detection limit of 10 fg/mL. In addition, the biosensor showed excellent specificity and repeatability. CONCLUSIONS: By constructing a Gr-FET device based on CVD-grown graphene and selecting a PA monoclonal antibody as the bio-recognition element, a highly sensitive, specific, and repeatable Gr-FET biosensor was successfully prepared for detecting extremely low concentrations of anthrax protective antigen (PA). This biosensor is expected to have a wide range of applications in clinical medicine and biological safety monitoring.
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Anthrax , Biosensing Techniques , Cardiovascular Diseases , Graphite , Humans , Anthrax/diagnosis , Biosensing Techniques/methods , Antibodies, MonoclonalABSTRACT
Detection of anthrax protective antigen is an effective way to diagnose anthracnose, and it plays an important part in the treatment of anthracnose. Affinity peptides, as a miniature biological recognition element, can quickly and effectively detect anthrax protective antigens. Based on computer-aided design technology (CAD), we have herein developed an affinity peptide design strategy for the detection of anthrax protective antigens. Firstly, six high-value mutation sites were determined based on the molecular docking between the template peptide and the receptor, and then the multi-site mutation of amino acids was carried out in order to establish a virtual peptide library. The library was selected by using molecular dynamics simulation and the best designed affinity peptide (code: P24) was found. The theoretical affinity with P24 peptide has increased by 19.8% compared with template peptide. Finally, the affinity with P24 peptide was measured by SPR technology to reach the nanomole level, which verified the effectiveness of the design strategy. The newly designed affinity peptide is expected to be used in the diagnosis of anthracnose.
Subject(s)
Anthrax , Humans , Molecular Docking Simulation , Antigens, Bacterial/genetics , Antigens, Bacterial/chemistry , PeptidesABSTRACT
OBJECTIVE: We intend to look at the link between remnant cholesterol (RC) and nonalcoholic fatty liver disease (NAFLD). We hypothesise that there may be a positive and nonlinear relationship between RC and NAFLD. METHODS: The information for this investigation was obtained from the National Health and Nutrition Examination Survey 2017-2020 database. The RC value was obtained by subtracting the sum of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) from the total cholesterol (TC) level. NAFLD diagnosis was based on ultrasonography results. RESULTS: The analysis included 3370 participants and observed a positive relationship between RC and NAFLD, after adjusting for confounders. A non-linear association between RC and NAFLD was also identified in the research, with an inflection point of 0.96 mmol/l. The effect sizes of 3.88 (2.43 to 6.2) and 0.59 (0.21 to 1.71) were determined on the left and right sides of the inflection point, respectively. In subgroup analysis, we identified age (P for interaction = 0.0309) and waist circumference (P for interaction = 0.0071) as interaction factors. CONCLUSIONS: Elevated RC levels were found to be linked to NAFLD, even after controlling for traditional risk factors. Moreover, non-linear pattern in the relationship between RC and NAFLD was also identified.