ABSTRACT
Sequencing-based mapping of ensemble pairwise interactions among regulatory elements support the existence of topological assemblies known as promoter-enhancer hubs or cliques in cancer. Yet, prevalence, regulators, and functions of promoter-enhancer hubs in individual cancer cells remain unclear. Here, we systematically integrated functional genomics, transcription factor screening, and optical mapping of promoter-enhancer interactions to identify key promoter-enhancer hubs, examine heterogeneity of their assembly, determine their regulators, and elucidate their role in gene expression control in individual triple negative breast cancer (TNBC) cells. Optical mapping of individual SOX9 and MYC alleles revealed the existence of frequent multiway interactions among promoters and enhancers within spatial hubs. Our single-allele studies further demonstrated that lineage-determining SOX9 and signaling-dependent NOTCH1 transcription factors compact MYC and SOX9 hubs. Together, our findings suggest that promoter-enhancer hubs are dynamic and heterogeneous topological assemblies, which are controlled by oncogenic transcription factors and facilitate subtype-restricted gene expression in cancer.
Subject(s)
Enhancer Elements, Genetic , Gene Expression Regulation, Neoplastic , Promoter Regions, Genetic , SOX9 Transcription Factor , Triple Negative Breast Neoplasms , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/pathology , Humans , SOX9 Transcription Factor/genetics , SOX9 Transcription Factor/metabolism , Cell Line, Tumor , Female , Transcription Factors/genetics , Transcription Factors/metabolism , Proto-Oncogene Proteins c-myc/genetics , Proto-Oncogene Proteins c-myc/metabolism , Oncogenes , Receptor, Notch1/genetics , Receptor, Notch1/metabolismABSTRACT
Purpose: Emerging research indicates a link between the intake of fatty fish and age-related macular degeneration (AMD). However, observational studies fall short in establishing a direct causal link between oily fish intake and AMD. We wanted to determine whether causal association lies between oily fish intake and age-related macular degeneration (AMD) risk in human beings. Methods: This two-sample mendelian randomization (MR) study used the MR method to probe the genetic causality in the relationship between oily fish intake and AMD. The genome-wide association study (GWAS) data for AMD were acquired from a Finnish database, whereas the data on fish oil intake came from the UK Biobank. The analysis used several approaches such as inverse-variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode MR. In addition, the Cochran's Q test was used to evaluate heterogeneity in the MR data. The MR-Egger intercept and MR-pleiotropy residual sum and outlier (MR-PRESSO) tests were used to assess the presence of horizontal pleiotropy. A leave-one-out sensitivity analysis was conducted to determine the reliability of the association. Results: The IVW method revealed that the intake of oily fish is an independent risk factor for AMD (P = 0.034). It also suggested a minimal likelihood of horizontal pleiotropy affecting the causality (P > 0.05), with no substantial heterogeneity detected in the genetic variants (P > 0.05). The leave-one-out analysis confirmed the reliability and stability of this correlation. Conclusions: This research used a two-sample MR analysis to provide evidence of a genetic causal relationship between the eating of oily fish and AMD. This discovery held potential significance in AMD prevention.
Subject(s)
Fish Oils , Genome-Wide Association Study , Macular Degeneration , Mendelian Randomization Analysis , Mendelian Randomization Analysis/methods , Macular Degeneration/genetics , Macular Degeneration/epidemiology , Macular Degeneration/etiology , Humans , Fish Oils/administration & dosage , Risk Factors , Polymorphism, Single Nucleotide , Animals , Genetic Predisposition to Disease , Fishes/genetics , Finland/epidemiologyABSTRACT
BACKGROUND: Lignocellulose is a renewable and sustainable resource used to produce second-generation biofuel ethanol to cope with the resource and energy crisis. Furfural is the most toxic inhibitor of Saccharomyces cerevisiae cells produced during lignocellulose treatment, and can reduce the ability of S. cerevisiae to utilize lignocellulose, resulting in low bioethanol yield. In this study, multiple rounds of progressive ionizing radiation was combined with adaptive laboratory evolution to improve the furfural tolerance of S. cerevisiae and increase the yield of ethanol. RESULTS: In this study, the strategy of multiple rounds of progressive X-ray radiation combined with adaptive laboratory evolution significantly improved the furfural tolerance of brewing yeast. After four rounds of experiments, four mutant strains resistant to high concentrations of furfural were obtained (SCF-R1, SCF-R2, SCF-R3, and SCF-R4), with furfural tolerance concentrations of 4.0, 4.2, 4.4, and 4.5 g/L, respectively. Among them, the mutant strain SCF-R4 obtained in the fourth round of radiation had a cellular malondialdehyde content of 49.11 nmol/mg after 3 h of furfural stress, a weakening trend in mitochondrial membrane potential collapse, a decrease in accumulated reactive oxygen species, and a cell death rate of 12.60%, showing better cell membrane integrity, stable mitochondrial function, and an improved ability to limit reactive oxygen species production compared to the other mutant strains and the wild-type strain. In a fermentation medium containing 3.5 g/L furfural, the growth lag phase of the SCF-R4 mutant strain was shortened, and its growth ability significantly improved. After 96 h of fermentation, the ethanol production of the mutant strain SCF-R4 was 1.86 times that of the wild-type, indicating that with an increase in the number of irradiation rounds, the furfural tolerance of the mutant strain SCF-R4 was effectively enhanced. In addition, through genome-transcriptome analysis, potential sites related to furfural detoxification were identified, including GAL7, MAE1, PDC6, HXT1, AUS1, and TPK3. CONCLUSIONS: These results indicate that multiple rounds of progressive X-ray radiation combined with adaptive laboratory evolution is an effective mutagenic strategy for obtaining furfural-tolerant mutants and that it has the potential to tap genes related to the furfural detoxification mechanism.
ABSTRACT
A new transfer approach was proposed to share calibration models of the hexamethylenetetramine-acetic acid solution for studying hexamethylenetetramine concentration values across different near-infrared (NIR) spectrometers. This approach combines Savitzky-Golay first derivative (S_G_1) and orthogonal signal correction (OSC) preprocessing, along with feature variable optimization using an adaptive chaotic dung beetle optimization (ACDBO) algorithm. The ACDBO algorithm employs tent chaotic mapping and a nonlinear decreasing strategy, enhancing the balance between global and local search capabilities and increasing population diversity to address limitations observed in traditional dung beetle optimization (DBO). Validated using the CEC-2017 benchmark functions, the ACDBO algorithm demonstrated superior convergence speed, accuracy, and stability. In the context of a partial least squares (PLS) regression model for transferring hexamethylenetetramine-acetic acid solutions using NIR spectroscopy, the ACDBO algorithm excelled over alternative methods such as uninformative variable elimination, competitive adaptive reweighted sampling, cuckoo search, grey wolf optimizer, differential evolution, and DBO in efficiency, accuracy of feature variable selection, and enhancement of model predictive performance. The algorithm attained outstanding metrics, including a determination coefficient for the calibration set (Rc2) of 0.99999, a root mean square error for the calibration set (RMSEC) of 0.00195%, a determination coefficient for the validation set (Rv2) of 0.99643, a root mean squared error for the validation set (RMSEV) of 0.03818%, residual predictive deviation (RPD) of 16.72574. Compared to existing OSC, slope and bias correction (S/B), direct standardization (DS), and piecewise direct standardization (PDS) model transfer methods, the novel strategy enhances the accuracy and robustness of model predictions. It eliminates irrelevant background information about the hexamethylenetetramine concentration, thereby minimizing the spectral discrepancies across different instruments. As a result, this approach yields a determination coefficient for the prediction set (Rp2) of 0.96228, a root mean squared error for the prediction set (RMSEP) of 0.12462%, and a relative error rate (RER) of 17.62331, respectively. These figures closely follow those obtained using DS and PDS, which recorded Rp2, RMSEP, and RER values of 0.97505, 0.10135%, 21.67030, and 0.98311, 0.08339%, 26.33552, respectively. Unlike conventional methods such as OSC, S/B, DS, and PDS, this novel approach does not require the analysis of identical samples across different instruments. This characteristic significantly broadens its applicability for model transfer, which is particularly beneficial for transferring specific measurement samples.
ABSTRACT
Introduction: Sweet sorghum juice is a typical production feedstock for natural, eco-friendly sweeteners and beverages. Clostridium tyrobutyricum is one of the widely used microorganisms in the food industry, and its principal product, bio-butyric acid is an important food additive. There are no published reports of Clostridium tyrobutyricum producing butyric acid using SSJ as the sole substrate without adding exogenous substances, which could reach a food-additive grade. This study focuses on tailoring a cost-effective, safe, and sustainable process and strategy for their production and application. Methods: This study modeled the enzymolysis of non-reducing sugars via the first/second-order kinetics and added food-grade diatomite to the hydrolysate. Qualitative and quantitative analysis were performed using high-performance liquid chromatography, gas chromatography-mass spectrometer, full-scale laser diffraction method, ultra-performance liquid chromatography-tandem mass spectrometry, the cell double-staining assay, transmission electron microscopy, and Oxford nanopore technology sequencing. Quantitative real-time polymerase chain reaction, pathway and process enrichment analysis, and homology modeling were conducted for mutant genes. Results: The treated sweet sorghum juice showed promising results, containing 70.60 g/L glucose and 63.09 g/L fructose, with a sucrose hydrolysis rate of 98.29% and a minimal sucrose loss rate of 0.87%. Furthermore, 99.62% of the colloidal particles and 82.13% of the starch particles were removed, and the concentrations of hazardous substances were effectively reduced. A food microorganism Clostridium tyrobutyricum TGL-A236 with deep utilization value was developed, which showed superior performance by converting 30.65% glucose and 37.22% fructose to 24.1364 g/L bio-butyric acid in a treated sweet sorghum juice (1:1 dilution) fermentation broth. This titer was 2.12 times higher than that of the original strain, with a butyric acid selectivity of 86.36%. Finally, the Genome atlas view, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and evolutionary genealogy of genes: Non-supervised Orthologous (eggNOG) functional annotations, three-dimensional structure and protein cavity prediction of five non-synonymous variant genes were obtained. Conclusion: This study not only includes a systematic process flow and in-depth elucidation of relevant mechanisms but also provides a new strategy for green processing of food raw materials, improving food microbial performance, and ensuring the safe production of food additives.
ABSTRACT
Paclitaxel, a diterpenoid isolated from the bark of Taxus wallichiana var. chinensis (Pilger) Florin, is currently showing significant therapeutic effects against a variety of cancers. Baccatin III (Bac) and 10-Deacetylbaccatin III (10-DAB) are in great demand as important precursors for the synthesis of paclitaxel. This work aims to develop a simple, rapid and highly selective, safe, and non-polluting molecularly imprinted material for 10-DAB and Bac enrichment. In this study, we innovatively prepared molecularly imprinted materials with nanocellulose aerogel microspheres and 2-vinylpyridine (2-VP) as a bifunctional monomer, and 10-DAB and Bac as bis-template molecules. In particular, functionalized nanocellulose dual-template molecularly imprinted aerogel microsphere (FNCAG-DMIM) were successfully synthesized by the bifunctional introduction of functional nanocellulose aerogel microsphere (FNCAG) modified with Polyethyleneimine (PEI) as a carrier and functional monomer, which provided a large number of recognition sites for bimodal molecules. FNCAG-DMIM showed high specificity for 10-DAB and Bac specific assays. Under the optimal experimental conditions, the adsorption capacities of FNCAG-DMIM for 10-DAB and Bac reached 52.27 mg g-1 and 53.81 mg g-1, respectively. In addition, it showed good reliability and practicality in the determination of real samples. The present study extends the research on the synthesis of natural functional monomers by molecularly imprinted materials and opens up new horizons for the targeted isolation of plant compounds by dual-template molecularly imprinted materials.
Subject(s)
Cellulose , Gels , Microspheres , Molecular Imprinting , Cellulose/chemistry , Cellulose/analogs & derivatives , Gels/chemistry , Molecular Imprinting/methods , Adsorption , Taxoids/chemistryABSTRACT
Bacteriophages have evolved diverse strategies to overcome host defence mechanisms and to redirect host metabolism to ensure successful propagation. Here we identify a phage protein named Dap1 from Pseudomonas aeruginosa phage PaoP5 that both modulates bacterial host behaviour and contributes to phage fitness. We show that expression of Dap1 in P. aeruginosa reduces bacterial motility and promotes biofilm formation through interference with DipA, a c-di-GMP phosphodiesterase, which causes an increase in c-di-GMP levels that trigger phenotypic changes. Results also show that deletion of dap1 in PaoP5 significantly reduces genome packaging. In this case, Dap1 directly binds to phage HNH endonuclease, prohibiting host Lon-mediated HNH degradation and promoting phage genome packaging. Moreover, PaoP5Δdap1 fails to rescue P. aeruginosa-infected mice, implying the significance of dap1 in phage therapy. Overall, these results highlight remarkable dual functionality in a phage protein, enabling the modulation of host behaviours and ensuring phage fitness.
Subject(s)
Phage Therapy , Pseudomonas Infections , Pseudomonas Phages , Pseudomonas aeruginosa , Viral Proteins , Pseudomonas aeruginosa/virology , Pseudomonas aeruginosa/pathogenicity , Pseudomonas aeruginosa/genetics , Animals , Mice , Pseudomonas Phages/genetics , Pseudomonas Phages/physiology , Pseudomonas Infections/therapy , Pseudomonas Infections/microbiology , Pseudomonas Infections/immunology , Virulence , Viral Proteins/genetics , Viral Proteins/metabolism , Biofilms/growth & development , Cyclic GMP/metabolism , Cyclic GMP/analogs & derivatives , Female , Bacteriophages/physiology , Bacteriophages/geneticsABSTRACT
Exosomes, as novel biomarker for liquid biopsy, exhibit huge important potential value for cancer diagnosis. However, various proteins show different expression levels on exosomal membrane, and the absolute concentration of exosomes in clinical samples is easily influenced by a number of factors. Here, we developed a CRISPR/Cas12a and aptamer-chemiluminescence based analysis (CACBA) for the relative abundance determination of tumor-related protein positive exosomes in plasma for breast cancer diagnosis. The total concentration of exosomes was determined through captured CD63 using a CRISPR/Cas12a-based method with the LoD of 8.97 × 103 particles/µl. Meanwhile, EpCAM and MUC1 positive exosomes were quantitatively detected by aptamer-chemiluminescence (ACL) based method with the LoD of 1.45 × 102 and 3.73 × 102 particles/µl, respectively. It showed that the percentages of EpCAM and MUC1 positive exosomes offered an excellent capability to differentiate breast cancer patients and healthy donors. The high sensitivity, strong specificity, outstanding anti-interference capability, and steady recovery rate of this approach offered higher accuracy and robustness than the commercialized method in clinical trial. In addition with good stability, easy preparation and low cost, this method not only provides a new approach to rapid analysis of exosome proteins, it may be quickly extended to the diagnoses of various cancers.
Subject(s)
Aptamers, Nucleotide , Biomarkers, Tumor , Biosensing Techniques , Breast Neoplasms , CRISPR-Cas Systems , Epithelial Cell Adhesion Molecule , Exosomes , Mucin-1 , Humans , Breast Neoplasms/diagnosis , Breast Neoplasms/blood , Breast Neoplasms/genetics , Exosomes/chemistry , Exosomes/genetics , Female , Aptamers, Nucleotide/chemistry , Biosensing Techniques/methods , Mucin-1/blood , Mucin-1/genetics , Mucin-1/analysis , Biomarkers, Tumor/blood , Biomarkers, Tumor/genetics , Epithelial Cell Adhesion Molecule/genetics , Luminescent Measurements/methods , Tetraspanin 30 , Limit of DetectionABSTRACT
Exosomes constitute an emerging biomarker for cancer diagnosis because they carry multiple proteins that reflect the origins of the parent cell. The highly sensitive detection of exosomes is a crucial prerequisite for the diagnosis of cancer. In this study, we report an exosome detection system based on quantum weak value amplification (WVA). The WVA detection system consists of a reflection detection light path and a Zr-ionized biochip. Zr-ionized biochips effectively capture exosomes through the specific interaction between zirconium dioxide and the phosphate groups on the lipid bilayer of exosomes. Aptamer-modified gold nanoparticles (Au NPs) are then used to specifically recognize proteins on exosomes to enhance the detection signal. The sensitivity and resolution of the detection system are 2944.07 nm/RIU and 1.22 × 10-5 RIU, respectively. The concentration of exosomes can be directly quantified by the WVA system, ranging from 105-107 particles/mL with the detection limit of 3 × 104 particles/mL. The use of Au NPs-EpCAM for the specific enhancement of breast cancer MDA-MB-231 exosomes is demonstrated. The results indicate that the WVA detection system can be a promising candidate for the detection of exosomes as tumor markers.
Subject(s)
Biosensing Techniques , Breast Neoplasms , Exosomes , Gold , Metal Nanoparticles , Humans , Breast Neoplasms/diagnosis , Female , Gold/chemistry , Metal Nanoparticles/chemistry , Biomarkers, Tumor , Cell Line, Tumor , Limit of Detection , Zirconium/chemistryABSTRACT
Clostridium butyricum (C. butyricum) represents a new generation of probiotics, which is beneficial because of its good tolerance and ability to produce beneficial metabolites, such as short-chain fatty acids and enzymes; however, its low enzyme activity limits its probiotic efficacy. In this study, a mutant strain, C. butyricum FZM 240 was obtained using carbon ion beam irradiation, which exhibited greatly improved enzyme production and tolerance. The highest filter paper, endoglucanase, and amylase activities produced by C. butyricum FZM 240 were 125.69â¯U/mL, 225.82â¯U/ mL, and 252.28â¯U/mL, which were 2.58, 1.95, and 2.21-fold higher, respectively, than those of the original strain. The survival rate of the strain increased by 11.40 % and 5.60 % after incubation at 90 °C for 5â¯min and with simulated gastric fluid at pH 2.5 for 2â¯h, respectively, compared with that of the original strain. Whole-genome resequencing and quantitative real-time PCR(qRT-PCR) analysis showed that the expression of genes related to enzyme synthesis (GE000348, GE001963 and GE003123) and tolerance (GE001114) was significantly up-regulated, while that of genes related to acid metabolism (GE003450) was significantly down-regulated. On this basis, homology modeling and functional prediction of the proteins encoded by the mutated genes were performed. According to the results, the properties related to the efficacy of C. butyricum as a probiotic were significantly enhanced by carbon ion beam irradiation, which is a novel strategy for the application of Clostridium spp. as feed additives.
Subject(s)
Clostridium butyricum , Mutation , Probiotics , Clostridium butyricum/genetics , Clostridium butyricum/metabolism , Clostridium butyricum/radiation effects , Carbon/metabolism , Animals , Cellulase/metabolism , Cellulase/genetics , Amylases/metabolism , Amylases/genetics , Bacterial Proteins/genetics , Bacterial Proteins/metabolismABSTRACT
Background: A traditional Chinese medicine (TCM) formula, containing Astragalus membranaceus (Fisch.) Bunge, Aconitum wilsonii Stapf ex Veitch, Curcuma longa L., and Radix ophiopogonis (AACO), has therapeutic value for the treatment of chronic heart failure (CHF). Objective: This study intends to explore the pharmacological mechanism underlying the activity of the AACO formula against CHF. Materials and Methods: Using the TCM Systems Pharmacology database and Bioinformatics Analysis Tool for Molecular Mechanism of TCM, the active ingredients contained in the herbs of the AACO formula were screened. Meanwhile, the target genes related to these active ingredients were identified and genes correlated with CHF were screened. Protein-protein interaction networks were built to elucidate the relationships between the AACO formula and CHF. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway enrichment analysis were carried out using the DAVID database. A "drug-component-target-disease" network was constructed with Cytoscape 3.7.0. The therapeutic effect of the AACO formula was proven by hemodynamic study, echocardiography evaluation, and histological analysis in transverse aortic constriction-induced CHF mice and was validated in vitro. Results: A total of 105 active ingredients and 1026 related targets were screened and identified, and 240 related targets overlapping with CHF were selected. According to GO analysis, the enriched genes participated in gene expression and cardiac contraction regulation by Ca2+ regulation. From KEGG analysis, the calcium axis was identified as one of the main mechanisms through which the AACO formula exerts an anti-CHF effect. AACO was validated to significantly improve cardiac diastolic and systolic functions in vivo via an increase in the rate of Ca2+ reuptake of the myocardial sarcoplasmic reticulum and improved myocardial contractility in vitro. Conclusions: Network pharmacology is a convenient method to study the complex pharmacological mechanisms of TCM. The calcium axis likely participates in the anti-CHF mechanism of AACO.
ABSTRACT
INTRODUCTION: As the second leading cause of death and disability worldwide, stroke is mainly caused by atherosclerosis and cardiac embolism, particularly in older individuals. Nevertheless, in young and otherwise healthy individuals, the causes of stroke can be more diverse and may include conditions such as patent foramen ovale, vasculitis, coagulopathies, genetic factors, or other undetermined causes. Although these other causes of stroke account for a relatively small proportion compared to ischemic stroke, they are becoming increasingly common in clinical practice and deserve attention. Here, we present a rare female patient with polycythemia vera (PV) who was admitted to the hospital as a stroke patient without any previous medical history. PATIENT CONCERNS: A 40-year-old young woman felt sudden dizziness and slow response. After 4 days of being admitted, she developed blurry vision on the right. DIAGNOSES: Cranial magnetic resonance imaging revealed aberrant signals in the left temporal and parietal lobe, as well as multiple small focal signal abnormalities were observed in the left frontal lobe. Magnetic resonance angiography revealed partial stenosis of the left internal carotid artery. The patient's blood routine examination revealed a significant elevation in complete blood counts, particularly the increase in red blood cells, as well as prolonged clotting time. An abdominal ultrasound and abdomen computed tomography showed splenomegaly. The outcome of the genetic testing was positive for the Janus kinase JAK2 exon V617F mutation (JAK2/V617F). The patient was diagnosed with PV-related stroke. INTERVENTIONS: The patient was treated with phlebotomy, cytoreductive therapy, and low-dose aspirin antiplatelet therapy and was regularly followed up in hematology and neurology clinics after discharge. OUTCOMES: The patient's red blood cell, leukocyte, and thrombocyte counts had fully normalized, with her hemoglobin level measuring at 146 g/L and hematocrit value at 43%. Furthermore, there had been a significant improvement in neurological symptoms. LESSONS: PV, a rare hematological disorder, can present with ischemic stroke as the initial performance, and the diagnosis mainly relies on routine blood tests, bone marrow biopsies, and genetic test. Therefore, clinicians should pay attention to PV, a low-prevalence disease, when encountering stroke in youth.
Subject(s)
Ischemic Stroke , Polycythemia Vera , Female , Humans , Young Adult , Aged , Adolescent , Adult , Male , Polycythemia Vera/complications , Polycythemia Vera/diagnosis , Polycythemia Vera/genetics , Ischemic Stroke/diagnosis , Ischemic Stroke/etiology , Ischemic Stroke/therapy , Janus Kinase 2/genetics , Bone Marrow/pathology , MutationABSTRACT
BACKGROUND: Cortisol is a steroid hormone secreted mainly by the adrenal cortex and is associated with chronic stress levels in the body. Hair cortisol concentration (HCC) is a reliable index to assess human stress levels. So far, no study has reported whether COVID-19 vaccination is associated with the changes of HCC. METHODS: Hair samples were collected from 114 college students at Hangzhou City University and Zhejiang University. Among them, 57 cases completed COVID-19 vaccination and others did not. HCCs were measured by the chemiluminescence immunoassay (CLIA). The psychological stress levels were evaluated using the Chinese College Student Psychological Stress Scale (CCSPSS). General information and adverse reactions of the subjects were collected by questionnaire. RESULTS: Compared with the vaccinated college students, the unvaccinated students had higher HCC levels in both A and B hair segments respectively corresponding older or six weeks before and newer or six weeks after vaccination (p < 0.05), reflecting higher stress levels. Besides, the vaccinated group had significantly higher HCCs in segment B compared with segment A (p < 0.05). Further analysis showed that the value of ΔHCC (HCCseg.B - HCCseg.A) of the vaccinated group was strongly associated with COVID-19 vaccination (p < 0.05), but was not associated with age, gender, BMI, CCSPSS score, hormone use, exercise frequency, hair washing frequency, or hair treatment. Finally, the number of self-reported systemic adverse reactions in the vaccinated group was associated with ΔHCC (p < 0.01). CONCLUSION: The COVID-19 vaccination had an impact on the value of HCC, which might be linked to the occurrence of systemic adverse effects following vaccinations.
Subject(s)
COVID-19 , Hydrocortisone , Humans , Hydrocortisone/analysis , COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Stress, Psychological/psychology , Hair , Vaccination/adverse effectsABSTRACT
Nitric acid, an important basic chemical raw material, plays an important role in promoting the development of national economy. However, such liquid hazardous chemicals are easy to cause accidental leakage during production, transportation, storage and use. The high concentration and corrosive toxic gas generated from decomposition shows tremendous harm to the surrounding environment and human life safety. Therefore, how to inhibit the volatilization of nitric acid and effectively control and block the generation of the toxic gas in the first time are the key to deal with the nitric acid leakage accident. Herein, a new method of molecular film obstruction is proposed to inhibit the nitric acid volatilization. The molecular film inhibitor spontaneously spread and form an insoluble molecular film on the gas-liquid interface, changing the state of nitric acid liquid surface and inhibiting the volatilization on the molecular scale. The inhibition rate up to 96% can be achieved below 45 °C within 400 min. Cluster structure simulation and energy barrier calculation is performed to elucidate the inhibition mechanism. Theoretical analysis of energy barrier shows that the specific resistance of the inhibitor significantly increased to 460 s·cm-1 at 45 °C, and the generated energy barrier is about 17,000 kJ·mol-1, which is much higher than the maximum energy required for nitric acid volatilization of 107.97 kJ·mol-1. The molecular film obstruction strategy can effectively inhibit the volatilization of nitric acid. This strategy paves the way for preventing the volatilization of liquid hazardous chemicals in accidental leakage treatment.
Subject(s)
Models, Theoretical , Nitric Acid , Humans , Volatilization , Hazardous Substances/toxicityABSTRACT
BACKGROUND: The safety and efficacy of intravenous thrombolysis (IVT) in acute ischemic stroke patients with large vessel occlusions and mild neurological deficits are controversial. METHODS: Data of stroke patients presenting with mild initial stroke, which was defined as the National Institutes of Health Stroke Scale score (NIHSS) ≤5 and large vessel occlusion, were extracted from a large provincewide stroke registry. RESULTS: A total of 619 IVT and 2170 non-IVT patients were identified in this study. IVT patients had higher rates of favorable functional outcome Modified Rankin Scale(mRS) ≤1 (74.6% vs. 70.6%; P =0.047), lower mRS scores (1 vs. 1, P =0.001), and higher NIHSS score decreased (1 vs. 0, P <0.001) at discharge compared with the non-IVT patients. The rates were similar in symptomatic intracranial hemorrhage (2.1% vs. 2.0%, P =0.853), severe systemic bleeding (0.8% vs. 0.6%, P =0.474), and mortality at discharge (0.2% vs. 0.2%, P =0.906) between the 2 groups. A multiple Logistic regression model found that age above 80 years [adjusted OR (aOR) 2.056 (95% CI, 1.125 to 3.756)], history of stroke [aOR 1.577 (95% CI, 1.303 to 1.910)], hyperlipidemia [aOR 2.156 (95% CI, 1.059 to 4.388)], high admission NIHSS score [aOR 1.564 (95% CI, 1.473 to 1.611)], and non-IVT [aOR 1.667 (95% CI, 1.337 to 2.077)] were independent risk factors for mRS >1. CONCLUSIONS: IVT administration is safe and effective in eligible acute ischemic stroke patients. Age above 80 years, with a history of stroke and hyperlipidemia, high admission NIHSS score, and non-IVT were independent risk factors for mRS >1 at discharge in these patients.
Subject(s)
Brain Ischemia , Hyperlipidemias , Ischemic Stroke , Stroke , Humans , Aged, 80 and over , Ischemic Stroke/etiology , Treatment Outcome , Stroke/etiology , Thrombolytic Therapy/methods , Hyperlipidemias/complications , Hyperlipidemias/drug therapy , Fibrinolytic Agents/therapeutic use , Brain Ischemia/complicationsABSTRACT
OBJECTIVE: Tissue injury and inflammation are two potential outcomes of cerebral ischemia-reperfusion (I/R) injury. Salvianolic acid B (Sal B), isolated from the roots of Salvia miltiorrhiza, is one of the major water-soluble compounds with a wide range of pharmacological effects including antioxidant, anti-inflammatory, antiproliferative, and neuroprotective effects. In the present study, we explored the neuroprotective effects and potential mechanisms of Sal B after I/R injury. METHODS: We induced cerebral ischemia in male CD-1 mice through transient (60 min) middle cerebral artery occlusion (tMCAO), and then injected Sal B (30 mg/kg) intraperitoneally. Neurological deficits, infarct volumes, and brain edema were assessed at 24 and 72 h after tMCAO. We detected the expression of Toll-like receptor 4 (TLR4), phosphorylated-p38 mitogen-activated protein kinase (P-p38 MAPK), phosphorylated c-Jun amino (N)-terminal kinases (p-JNK), nuclear factor-κB (NF-κB), and interleukin-1ß (IL-1ß) in the brain tissue. RESULTS: Compared with the tMCAO group, Sal B significantly improved neurological deficits, reduced infarct size, attenuated cerebral edema, and downregulated the expression of pro-inflammatory mediators TLR4, p-p38MAPK, p-JNK, nuclear NF-κB, and IL-1ß in brain tissue after I/R injury. CONCLUSION: We found that Sal B protects brain tissues from I/R injury by activating its anti-inflammatory properties.
Subject(s)
Brain Ischemia , Neuroprotective Agents , Reperfusion Injury , Animals , Male , Mice , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Brain Ischemia/drug therapy , Down-Regulation , Infarction , Interleukin-1beta/genetics , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , NF-kappa B/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism , Reperfusion Injury/drug therapy , Reperfusion Injury/metabolism , Signal Transduction , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolismABSTRACT
In previous studies, prothrombin time (PT), systemic inflammation response index (SIRI) and systemic immune inflammation Index (SII) levels might be the prognostic factors for patients with ischemic stroke. However, the association between these coagulation and inflammation biomarkers and prognosis in patients with acute ischemic stroke (AIS) who undergo intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) remains unclear and needs further study. Thus, this study aimed to investigate the relationship between these biomarkers and clinical prognosis after IVT in AIS patients. We included patients at the Hebei general hospital diagnosed with AIS who received standard-dose IVT with rt-PA from September 2017 to August 2022. Demographic information, vascular risk factors, laboratory test results, and other stroke-related data were collected for analysis. Clinical outcomes included short-term outcome at 24 h and functional outcome at 3 months. We enrolled 281 patients in this study. In total, 16 patients had END within 24 h, and 106 patients had an unfavorable outcome at the 3-month visit. In the multivariate analysis, PT level (OR = 1.833; 95% CI: 1.161-2.893; P = 0.009), SIRI level (OR = 2.166; 95% CI: 1.014-4.629; P = 0.046) and SII level (OR = 1.002; 95% CI: 1.000-1.003; P = 0.021) were independently associated with 3-month poor outcome in AIS patients with IVT. In conclusion, the higher PT, SIRI and SII levels were independently associated with poor prognosis in AIS patients after IVT. Additionally, PT, SIRI and SII all can be novel short-term prognostic biomarkers for AIS patients treated with IVT.
Subject(s)
Brain Ischemia , Ischemic Stroke , Stroke , Humans , Tissue Plasminogen Activator/therapeutic use , Prognosis , Ischemic Stroke/drug therapy , Prothrombin Time , Thrombolytic Therapy/adverse effects , Biomarkers , Inflammation/drug therapy , Inflammation/etiology , Fibrinolytic Agents/therapeutic use , Treatment OutcomeABSTRACT
Transcriptional dysregulation is a hallmark of cancer and can be driven by altered enhancer landscapes. Recent studies in genome organization have revealed that multiple enhancers and promoters can spatially coalesce to form dynamic topological assemblies, known as promoter-enhancer hubs, which strongly correlate with elevated gene expression. In this review, we discuss the structure and complexity of promoter-enhancer hubs recently identified in multiple cancer types. We further discuss underlying mechanisms driving dysregulation of promoter-enhancer hubs and speculate on their functional role in pathogenesis. Understanding the role of promoter-enhancer hubs in transcriptional dysregulation can provide insight into new therapeutic approaches to target these complex features of genome organization.
Subject(s)
Enhancer Elements, Genetic , Neoplasms , Humans , Enhancer Elements, Genetic/genetics , Promoter Regions, Genetic , Neoplasms/geneticsABSTRACT
In this article, thermosensitive molecularly imprinted polymer and composite aerogel were combined for the first time to create an intelligent temperature-responsive aerogel reactor to effectively enrich ursolic acid (UA). Because aerogel carrier had a higher specific surface area and higher porosity compared to other carriers, the ursolic acid molecularly imprinted intelligent temperature responsive aerogel reactor (ITR&AR(G570)&UA-MIP) demonstrated a higher adsorption capacity for UA. More notably, ITR&AR(G570)&UA-MIP have the extraordinary capacity to spontaneously adsorb-desorb target molecule UA by regulating the reaction temperature. The ratio of the target molecule UA to the functional monomer and crosslinker in the grafting process and external influences had a major impact on how ITR&AR(G570)&UA-MIP were prepared overall. When the molar ratio of UA to 4-VP was 1:8, the weight ratio between ITR&AR(G570)&UA-MIP and EGDMA/DVB was 1:2:10, the reaction temperature was 60 °C, and the ambient pH = 6, the material showed the best adsorption capacity, reaching a peak of about 70 mg g-1. After researching the appropriate synthesis conditions, ITR&AR(G570)&UA-MIP were applied to lingonberry (Vaccinium Vitis-Idaea L.) berry extracts in this work. The outcomes show that this technique provides a new, intelligent, temperature-controlled adsorption material for the solid-phase extraction of triterpenoid acids in natural products, with good specific adsorption performance for the target molecule UA.
Subject(s)
Cellulose , Molecular Imprinting , Polymers/chemistry , Molecular Imprinting/methods , Temperature , Adsorption , Solid Phase Extraction/methods , Ursolic AcidABSTRACT
The main issues with local delivery of cosmetics are their high sensitivity and limited drug loading of active pharmaceutical ingredient. Nanocrystal technology offers consumers cutting-edge and effective products and exhibits enormous development potential in the beauty business as a new delivery method to address the issue of low solubility and low permeability of sensitive chemicals. In this review, we described the processes for making NCs, along with the impacts of loading and the uses of different carriers. Among them, nanocrystalline loaded gel and emulsion are widely used and may further improve the stability of the system. Then, we introduced the beauty efficacy of drug NCs from five aspects: anti-inflammation and acne, anti-bacterial, lightening and freckle removal, anti-aging as well as UV protection. Following that, we presented the current scenario about stability and safety. Finally, the challenges and vacancy were discussed along with the potential uses of NCs in the cosmetics industry. This review serves as a resource for the advancement of nanocrystal technology in the cosmetics sector.