ABSTRACT
Traditional DNA walkers face enormous challenges due to limited biostability and reaction kinetics. Herein, we designed a self-driven close-looped DNAzyme walker (cl-DW) with high structural biostability and catalytic activity that enabled rapid electrochemiluminescence (ECL) detection of pesticide residue acetamiprid. Specifically, cl-DW exhibited increasing ability to resist nuclease degradation with a 570-fold longer half-degradation time than that of the single-stranded DNAzyme walker (ss-DW) due to the protected DNA terminal. Furthermore, cl-DW achieved high catalytic activity with a 4.3-fold faster reaction kinetic than that of ss-DW due to the circularized nanostructure of an available catalytic domain. Consequently, we utilized cl-DW as a signal amplifier and tin-based sulfide (SnS2) nanoflowers as ECL emitters to construct an ECL aptasensor, which realized the sensitive detection of acetamiprid with a limit of detection of 0.85 nM. This work provides a reliable approach to exploring DNA walkers with high catalytic activity and better biostability for molecular monitoring.
Subject(s)
Biosensing Techniques , DNA, Catalytic , Electrochemical Techniques , Luminescent Measurements , Neonicotinoids , Neonicotinoids/chemistry , Neonicotinoids/analysis , DNA, Catalytic/chemistry , Luminescent Measurements/methods , Catalytic Domain , Limit of Detection , Pesticide Residues/chemistry , Pesticide Residues/analysis , Aptamers, Nucleotide/chemistryABSTRACT
Apurinic/apyrimidinic endonuclease 1 (APE1), as a vital base excision repair enzyme, is essential for maintaining genomic integrity and stability, and its abnormal expression is closely associated with malignant tumors. Herein, we constructed an electrochemiluminescence (ECL) biosensor for detecting APE1 activity by combining nanoconfined ECL silver nanoclusters (Ag NCs) with X-shaped DNA recognizer-triggered cascade amplification. Specifically, the Ag NCs were prepared and confined in the glutaraldehyde-cross-linked chitosan hydrogel network using the one-pot method, resulting in a strong ECL response and exceptional stability in comparison with discrete Ag NCs. Furthermore, the self-assembled X-shaped DNA recognizers were designed for APE1 detection, which not only improved reaction kinetics due to the ordered arrangement of recognition sites but also achieved high sensitivity by utilizing the recognizer-triggered cascade amplification of strand displacement amplification (SDA) and DNAzyme catalysis. As expected, this biosensor achieved sensitive ECL detection of APE1 in the range of 1.0 × 10-3 U·µL-1 to 1.0 × 10-10 U·µL-1 with the detection limit of 2.21 × 10-11 U·µL-1, rendering it a desirable approach for biomarker detection.
Subject(s)
Biosensing Techniques , DNA-(Apurinic or Apyrimidinic Site) Lyase , Electrochemical Techniques , Luminescent Measurements , Metal Nanoparticles , Silver , DNA-(Apurinic or Apyrimidinic Site) Lyase/metabolism , DNA-(Apurinic or Apyrimidinic Site) Lyase/analysis , Silver/chemistry , Humans , Metal Nanoparticles/chemistry , Electrochemical Techniques/methods , Luminescent Measurements/methods , Biosensing Techniques/methods , Nucleic Acid Amplification Techniques/methods , DNA/chemistry , Limit of Detection , DNA, Catalytic/chemistry , DNA, Catalytic/metabolismABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: China and India have unique traditional medicine systems with vast territory and rich medical resources. Traditional medicines in China include traditional Chinese medicine, Tibetan medicine, Mongolian medicine, Uyghur medicine, Dai medicine, etc. In the third national survey of Chinese medicine resources, 12694 medicinal materials were identified. Traditional medicines in India include Ayurveda, Unani, Siddha, Homoeopathy, etc. There are 7263 medicinal materials in India. AIM OF THE STUDY: To reveal the characteristics of medicinal materials between China and India respectively, and to compare the similarities and differences in terms of properties, tastes, medicinal parts and therapeutic uses and to promote the exchange of traditional medicine between China and India and the international trade of traditional medicine industry. METHODS: The information of medicinal materials between China and India was extracted from The Chinese Traditional Medicine Resource Records and Pharmacopoeia of the People's Republic of China, as well as from 71 Indian herbal monographs. The information of each medicinal material, such as types, families, genera, properties, distribution, medicinal parts, efficacy, therapeutic uses, dosage form and dosage, was recorded in Excel for statistical analysis and visual comparison. RESULTS: A total of 12694 medicinal materials in China and 5362 medicinal materials in India were identified. The medicinal materials were mostly distributed in Southwest China and northern India. Plants were the main sources of medicinal materials. The common medicinal parts in China were whole medicinal materials, roots and rhizomes, and India used more renewable fruits, seeds and leaves. They are commonly used in the treatment of digestive system diseases. There were 1048 medicinal materials used by both China and India, which were distributed in 188 families and 685 genera. The Chinese and Indian pharmacopoeias had a total of 80 species of medicinal materials used by both China and India. CONCLUSIONS: The characteristics of medicinal materials between China and India were somewhat different, which was conducive to provide a reference basis for traditional medicine in China or India to increase the medicinal parts and indications when using a certain medicinal material, as well as to expand the source of medicine and introduce new resources. However, there were certain similarities and shared medicinal materials, which can tap the potential of bilateral trade of medicinal materials between China and India, so as to promote the medical cultural exchange and economic and trade cooperation between the two countries.
Subject(s)
Data Mining , Plants, Medicinal , India , China , Plants, Medicinal/chemistry , Humans , Data Mining/methods , Medicine, Chinese Traditional/methods , Medicine, Traditional/methods , Phytotherapy/methodsABSTRACT
Chimeric antigen receptor (CAR)-T-cell therapy has demonstrated considerable efficacy and safety in the treatment of patients with relapsed/refractory haematological malignancies. Owing to significant advances, CAR-T-cell therapeutic modality has undergone substantial shifts in its clinical application. Coagulation abnormalities, which are prevalent complications in CAR-T-cell therapy, can range in severity from simple abnormalities in coagulation parameters to serious haemorrhage or disseminated intravascular coagulation associated with life-threatening multiorgan dysfunction. Nonetheless, there is a lack of a comprehensive overview concerning the coagulation abnormalities associated with CAR-T-cell therapy. With an aim to attract heightened clinical focus and to enhance the safety of CAR-T-cell therapy, this review presents the characteristics of the coagulation abnormalities associated with CAR-T-cell therapy, including clinical manifestations, coagulation parameters, pathogenesis, risk factors and their influence on treatment efficacy in patients receiving CAR-T-cell infusion. Due to limited data, these conclusions may undergo changes as more experience accumulates.
Subject(s)
Blood Coagulation Disorders , Hematologic Neoplasms , Immunotherapy, Adoptive , Humans , Immunotherapy, Adoptive/adverse effects , Immunotherapy, Adoptive/methods , Hematologic Neoplasms/therapy , Blood Coagulation Disorders/therapy , Blood Coagulation Disorders/etiology , Receptors, Chimeric Antigen/therapeutic useABSTRACT
The presence of bone metastases (BM) in patients with lung cancer is indicative of a worse prognosis. The present study aims to investigate the risk factors associated with BM in patients with lung cancer. Patients with lung cancer admitted to the First Affiliated Hospital of Anhui Medical University between June 2019 and September 2021 were enrolled in this study. A nomogram was constructed based on the outcomes derived from univariate and multivariate analyses. Concordance index, calibration plots, receiver operating characteristic curves, and decision curve analysis were used to evaluate the nomogram. To substantiate the influence of monocytes on lung cancer BM, various assays, including cell co-culture, Transwell, wound-healing assays, and immunohistochemistry and immunofluorescence staining, were conducted. Statistical analyses were performed using SPSS 22.0 software and GraphPad Prism 7.0. A total of 462 eligible patients were enrolled, comprising 220 with BM and 242 without. Multivariate analysis revealed that histological type, medical history, monocyte percentage, and LDH (Lactate Dehydrogenase) and ALP (Alkaline Phosphatase) levels were independent risk factors for BM in lung cancer. Transwell and wound-healing assays indicated that co-culture with monocytes significantly enhanced the migration and invasion capabilities of A549 cells in vitro. Immunohistochemistry and immunofluorescence analyses demonstrated a noteworthy increase in monocyte infiltration in the primary lesions of patients with lung cancer with BM. In conclusion, this study successfully constructed and validated a precise, straightforward, and cost-effective prognostic nomogram for patients with lung cancer with BM.
ABSTRACT
Soil eukaryotes play an important role in regulating the ecological processes and ecosystem functioning. However, the recovery potential of soil eukaryotic diversity during wetland restoration is largely unknown. We compared the alpha and beta diversity of soil eukaryotes of farmlands and natural and restored wetlands to explore the underlying abiotic and biotic driving forces in the Sanjiang Plain, China. We found that there was no significant difference of the alpha diversity of soil eukaryotes, while the beta diversity of soil eukaryotes differed significantly between the three land use types, with the mean values in the restored wetlands in between those in the natural wetlands and farmlands. The composition of soil eukaryotic communities were less diverse in farmlands compared to restored and natural wetlands. Network property of soil eukaryotes community (positive: negative edges) increased from farmlands to restored wetlands to natural wetlands, indicating enhanced species positive: negative interactions during restoration. The structural equation modeling indicated that species positive: negative interactions and soil nutrients directly affected soil eukaryotic beta diversity. Soil pH and soil water content indirectly affected soil eukaryotic beta diversity by directly affecting species interactions. Our findings suggest that wetland restoration could change soil environment, strengthen microbial cooperation, and increase eukaryotic beta diversity. However, it may take a very long time to reach the original level of soil eukaryotic structure and diversity.
Subject(s)
Ecosystem , Wetlands , Soil/chemistry , Soil Microbiology , Water , ChinaABSTRACT
Herein, pyrenecarboxaldehyde@graphene oxide (Pyc@GO) sheets with highly efficient electrochemiluminescence (ECL) as emitters were prepared by a noncovalent combination to develop a neoteric ECL biosensing platform for the ultrasensitive assessment of human apurinic/apyrimidinic endonuclease1 (APE1) activity. Impressively, the pyrenecarboxaldehyde (Pyc) molecules were able to form stable polar functional groups on the surface of GO sheets through the noncovalent π-π stacking mechanism to prevent intermolecular restacking and simultaneously generate Pyc@GO sheets. Compared with the tightly packed PAH nanocrystals, the Pyc@GO sheets significantly reduced internal filtering effects and diminished nonactivated emitters to enhance ECL intensity and achieve strong ECL emission. Furthermore, the APE1-activated initiators could trigger the recyclable cascade amplified system based on the synergistic cross-activation between catalytic hairpin assembly (CHA) and DNAzyme, which improved the signal amplification and transduction ability. Consequently, the developed ECL platform for the detection of APE1 activity displayed exceptional sensitivity with a low detection limit of 4.6 × 10-9 U·mL-1 ranging from 10-8 to 10-2 U·mL-1. Therefore, the proposed strategy holds great promise for the future development of sensitive and reliable biosensing platforms for the detection of various biomarkers.
Subject(s)
DNA, Catalytic , Graphite , Nanoparticles , Humans , CatalysisABSTRACT
DNA nanostructure provides powerful tools for DNA demethylase activity detection, but its stability has been significantly challenged. By virtue of circular DNA with resistance to exonuclease degradation, herein, the circular DNAzyme duplex with artificial methylated modification was constructed to identify the target and output the DNA activators to drive the CRISPR/Cas12a, constructing an "on-off-on" electrochemiluminescence (ECL) biosensor for monitoring the activity of the O6-methylguanine-DNA methyltransferase (MGMT). Specifically, the circular DNAzyme duplex consisted of the chimeric RNA-DNA substrate ring with double activator sequences and two single-stranded DNAzymes, whose catalytic domains were premodified with the methyl groups. When the MGMT was present, the methylated DNAzymes were repaired and restored the catalytic activity to cleave the chimeric RNA-DNA substrates, followed by the output of DNA activators to initiate the CRISPR/Cas12a. Subsequently, the ECL signals of silver nanoparticle-modified SnO2 nanospheres (Ag@SnO2) were recovered by releasing the ferrocene-labeled quenching probes (Fc-DNA) from the electrode surface because of the trans-cleavage activity of CRISPR/Cas12a, thus achieving the specific and sensitive ECL detection of MGMT from 2.5 × 10-4 to 2.5 × 102 ng/mL with a low limit (9.69 × 10-5 ng/mL). This strategy affords novel ideas and insights into research on how to project stable nucleic acid probes to detect DNA demethylases beyond traditional methods.
Subject(s)
DNA, Catalytic , Metal Nanoparticles , DNA, Catalytic/chemistry , CRISPR-Cas Systems , Metal Nanoparticles/chemistry , Silver , DNA/chemistry , RNAABSTRACT
Whole milk powder and skimmed milk powder are suitable for different groups of people due to their differences in composition. Therefore, a rapid classification method for whole milk powder and skimmed milk powder is urgently needed. In this paper, a novel strategy based on laser-induced breakdown spectroscopy (LIBS) and feature processing methods combined with logistic regression (LR) was constructed for the classification of milk powder. A LR classification model based on mini-batch gradient descent (MGD) was employed first. As indicated by the research results, the accuracy of the MGD-LR model for the milk powder samples in the test set is 96.33% and the modeling time is 33.07 s. The modeling efficiency is low and needs to be improved. Principal components analysis (PCA) and mutual information (MI) were used as feature processing methods to reduce the high dimensional LIBS data into fewer features for improving the modeling efficiency of the classification model. The research results indicate that the accuracy of the PCA-MGD-LR model and the MI-MGD-LR model for the test set of milk powder samples was 99.33% and 99.67%, respectively. Compared with MGD-LR model, the modeling efficiency of PCA-MGD-LR and MI-MGD-LR models has increased by 89.7% and 74.8%, respectively. The results fully demonstrate the feasibility of rapid milk powder classification based on LIBS and feature processing methods combined with LR, and it will provide a new technology for the identification and classification of milk powder.
Subject(s)
Lasers , Milk , Humans , Animals , Milk/chemistry , Powders/analysis , Logistic Models , Spectrum Analysis/methodsABSTRACT
Laser-induced breakdown spectroscopy (LIBS) plays an increasingly important role in the classification and recycling of aluminum alloys owing to its outstanding elemental analysis performance. For LIBS measurements with sample surface fluctuations, consistently and exactly maintaining the laser and fiber focus points on the sample surface is difficult, and fluctuations in the focus severely affect the stability of the spectrum. In this study, a data transfer method is introduced to reduce the effect of spectral fluctuations on the model performance. During the experiment, a focal point is placed on the sample surface. Then, keeping experimental conditions unchanged, the three-dimensional platform is only moved up and down along the z-axis by 0.5 mm, 1 mm, 1.5 mm, 2 mm and 2.5 mm, respectively. Eleven spectral datasets at different heights are collected for analysis. The KNN model is used as the base classifier, and the accuracies of the 11 datasets, from the lowest to the highest, are 11.48%, 19.71%, 30.57%, 45.71%, 53.57%, 88.28%, 52.57%, 21.42%, 14.42%, 14.42%, and 14.42%. To improve predictive performance, the difference in data distribution between the spectra collected at the sample surface and those collected at other heights is reduced by data transfer. Feature selection is introduced and combined with data transfer, and the final accuracies are 78.14%, 82.28%, 80.14%, 89.71%, 91.85%, 98.42%, 94.28%, 92.42%, 82.14%, 78.57%, and 73.71%. It can be seen that the proposed method provides a new feasible and effective way for the classification of aluminum alloys in a real detection environment.
ABSTRACT
Functional DNA walkers with substantial nanostructures have been extensively investigated; however, their stability still faces challenges when exposed to diverse nuclease in clinical biological samples, resulting in the unreliability of actual assessment. This work proposed a target-driven annular DNA walker with enhanced stability enabling the sensitive and reliable response to different concentrations of apurinic/apyrimidinic endonuclease 1 (APE1), by preparing silicon quantum dots (SiQDs) as electrochemiluminescence (ECL) emitters. Specifically, the SiQDs showed significant strong and stable ECL signals by purifying the microenvironment of SiQDs through the dialysis removal of the gel-like layers surrounding the SiQDs. The relative standard deviation (RSD) of their ECL signal had been improved 16.59 times under consecutive scanning compared to that of SiQDs without dialysis, demonstrating a significant improvement in ECL stability. Subsequently, in the presence of APE1, the designed annular DNA walker was activated to move along the numerous quenching probes within the continuous cross-based DNA orbits, which were immobilized to the SiQD-modified electrode, providing ECL readout signals. The linear range of this ECL biosensor was 1.0 × 10-13 U·µL-1 to 1.0 × 10-7 U·µL-1, and the limit of detection (LOD) was as low as 1.766 × 10-14 U·µL-1. This work provides a novel structure of a DNA walker with nuclease resistance for clinical sample detection and designs a new strategy for synthesizing SiQDs with favorable ECL performance, tremendously expanding the ECL application of SiQDs.
Subject(s)
Biosensing Techniques , Quantum Dots , Quantum Dots/chemistry , Silicon/chemistry , Luminescent Measurements/methods , Electrochemical Techniques/methods , Renal Dialysis , DNA/chemistry , Biosensing Techniques/methods , Limit of DetectionABSTRACT
The master transcription factor receptor retinoic acid receptor-related orphan receptor γt (RORγt) regulates the differentiation of T-helper 17 (Th17) cells and the production of interleukin-17 (IL-17). Activation of RORγt+ T cells in the tumor microenvironment promotes immune infiltration to more effectively inhibit tumor growth. Therefore, RORγt agonists provide a reachable approach to cancer immunotherapy. Herein, a series of biaryl amide derivatives as novel RORγt agonists were designed, synthesized, and evaluated. Starting from the reported RORγt inverse agonist GSK805 (1), "functionality switching" and structure-based drug optimization led to the discovery of a promising RORγt agonist lead compound 14, which displayed potent and selective RORγt agonist activity and significantly improved metabolic stability. With excellent in vivo pharmacokinetic profiles, compound 14 demonstrated robust efficacy in preclinical tumor models of mouse B16F10 melanoma and LLC lung adenocarcinoma. Taken together, current studies indicate that 14 deserves further investigation as a potential lead RORγt agonist for cancer immunotherapy.
Subject(s)
Amides , Neoplasms , Mice , Animals , Amides/pharmacology , Amides/therapeutic use , Nuclear Receptor Subfamily 1, Group F, Member 3/agonists , Drug Inverse Agonism , Immunotherapy , Tumor MicroenvironmentABSTRACT
Quantification of liposoluble micronutrients in large-scale vegetable oil samples is urgently needed, because their health benefits are increasingly emphasized. However, current analytical methods are limited to either labor-intensive preparation processes or time-consuming chromatography separation. In this work, an online oil matrix separation strategy for direct, rapid, and simultaneous determination of squalene, tocopherols, and phytosterols in walnut oil (WO) was developed on the basis of the lipid class separation mode of supercritical fluid chromatography. A single run was completed in 13 min containing 6 min of column cleaning and balancing. Satisfactory limit of detections (0.05-0.20 ng/mL), limit of quantifications (0.15-0.45 ng/mL), recoveries (70.61-101.44%), and matrix effects (78.43-91.62%) were achieved, indicating the reliability of this method. In addition, eight sterol esters were identified in WO, which have not previously been reported. The proposed method was applied to characterize the liposoluble micronutrient profile of WO samples obtained from different walnut cultivars, geographical origins, and processes.
Subject(s)
Chromatography, Supercritical Fluid , Juglans , Phytosterols , Sterols/analysis , Squalene/analysis , Tocopherols/chemistry , Reproducibility of Results , Phytosterols/chemistry , Mass Spectrometry , Plant Oils/chemistryABSTRACT
Introduction: The investigation of cognitive function in microgravity, both short-term and long-term, remains largely descriptive. And the underlying mechanisms of the changes over time remain unclear. Methods: Behavioral tests, electrophysiological recording, and RNA sequencing were used to observe differences in behavior, synaptic plasticity, and gene expression. Results: Initially, we measured the performance of spatial cognition exposed to long-term simulated microgravity (SM). Both working memory and advanced cognitive abilities were enhanced. Somewhat surprisingly, the synaptic plasticity of the hippocampal CA3-CA1 synapse was impaired. To gain insight into the mechanism of changing regularity over time, transcriptome sequencing in the hippocampus was performed. The analysis identified 20 differentially expressed genes (DEGs) in the hippocampus after short-term modeling, 19 of which were up-regulated. Gene Ontology (GO) analysis showed that these up-regulated genes were mainly enriched in synaptic-related processes, such as Stxbp5l and Epha6. This might be related to the enhancement of working memory performance under short-term SM exposure. Under exposure to long-term SM, 7 DEGs were identified in the hippocampus, all of which were up-regulated and related to oxidative stress and metabolism, such as Depp1 and Lrg1. Compensatory effects occurred with increased modeling time. Discussion: To sum up, our current research indicates that the cognitive function under SM exposure is consistently maintained or potentially even being enhanced over both short and long durations. The underlying mechanisms are intricate and potentially linked to the differential expression of hippocampal-associated genes and alterations in synaptic function, with these effects being time-dependent. The present study will lay the experimental and theoretical foundation of the multi-level mechanism of cognitive function under space flight.
ABSTRACT
Milk powder can provide the necessary nutrients for the growth of infants, and the level of its energy value is an important factor in the measurement of its nutritional value. Therefore, the measurement of the energy value in milk powder is of great significance for the nutritional health of infants. In this study, samples of 32 different brands of milk powder were selected for spectral analysis, and laser-induced breakdown spectroscopy (LIBS) combined with deep belief network (DBN), back propagation (BP) neural network, and long short-term memory (LSTM) models was used to achieve quantitative analysis of the energy value of the milk powder. The experimental results revealed that the LSTM model outperformed the DBN and BP models in terms of accuracy, with a mean relative error (MREP) of 1.0029%, which was 73.03% lower than that of DBN (3.7186%) and 69.53% lower than that of BP (3.2914%). Moreover, the determination coefficient (RP2) value improved significantly from 0.9341 for DBN and 0.9766 for BP to 0.9984. In addition, the root mean square error (RMSEP) decreased to 0.2140 from 0.7042 for DBN and 0.9051 for BP. These results demonstrate that the LSTM model has superior predictive performance compared to the other models. Therefore, the combination of LIBS and LSTM can accurately measure the energy value of milk powder and provide an effective and feasible means for its commercial measurement.
Subject(s)
Memory, Short-Term , Milk , Infant , Humans , Animals , Powders , Memory, Long-Term , LasersABSTRACT
SYNGAP1 haploinsufficiency in humans leads to severe neurodevelopmental disorders characterized by intellectual disability, autism, epilepsy, and sensory processing deficits. However, the circuit mechanisms underlying these disorders are not well understood. In mice, a decrease of SynGAP levels results in cognitive deficits by interfering with the development of excitatory glutamatergic connections. Recent evidence suggests that SynGAP also plays a crucial role in the development and function of GABAergic inhibitory interneurons. Nevertheless, it remains uncertain whether and to what extent the expression of SYNGAP1 in inhibitory interneurons contributes to cortical circuit function and related behaviors. The activity of cortical neurons has not been measured simultaneously with behavior. To address these gaps, we recorded from layer 2/3 neurons in the primary whisker somatosensory cortex (wS1) of mice while they learned to perform a whisker tactile detection task. Our results demonstrate that mice with interneuron-specific SYNGAP1 haploinsufficiency exhibit learning deficits characterized by heightened behavioral responses in the absence of relevant sensory input and premature responses to unrelated sensory stimuli not associated with reward acquisition. These behavioral deficits are accompanied by specific circuit abnormalities within wS1. Interneuron-specific SYNGAP1 haploinsufficiency increases detrimental neuronal correlations directly related to task performance and enhances responses to irrelevant sensory stimuli unrelated to the reward acquisition. In summary, our findings indicate that a reduction of SynGAP in inhibitory interneurons impairs sensory representation in the primary sensory cortex by disrupting neuronal correlations, which likely contributes to the observed cognitive deficits in mice with pan-neuronal SYNGAP1 haploinsufficiency.SIGNIFICANCE STATEMENT SYNGAP1 haploinsufficiency leads to severe neurodevelopmental disorders. The exact nature of neural circuit dysfunction caused by SYNGAP1 haploinsufficiency remains poorly understood. SynGAP plays a critical role in the function of GABAergic inhibitory interneurons as well as glutamatergic pyramidal neurons in the neocortex. Whether and how decreasing SYNGAP1 level in inhibitory interneurons disrupts a behaviorally relevant circuit remains unclear. We measure neural activity and behavior in mice learning a perceptual task. Mice with interneuron-targeted disruption of SYNGAP1 display increased detrimental neuronal correlations and elevated responses to irrelevant sensory inputs, which are related to impaired task performance. These results show that cortical interneuron dysfunction contributes to sensory deficits in SYNGAP1 haploinsufficiency with important implications for identifying therapeutic targets.
Subject(s)
Neocortex , Humans , Mice , Animals , Neocortex/metabolism , Interneurons/physiology , Neurons/physiology , Pyramidal Cells/metabolism , Learning , ras GTPase-Activating Proteins/genetics , ras GTPase-Activating Proteins/metabolismABSTRACT
Background A simple measurement of central venous pressure (CVP)-mean by the digital monitor display has become increasingly popular. However, the agreement between CVP-mean and CVP-end (a standard method of CVP measurement by analyzing the waveform at end-expiration) is not well determined. This study was designed to identify the relationship between CVP-mean and CVP-end in critically ill patients and to introduce a new parameter of CVP amplitude (ΔCVP= CVPmax - CVPmin) during the respiratory period to identify the agreement/disagreement between CVP-mean and CVP-end.Methods In total, 291 patients were included in the study. CVP-mean and CVP-end were obtained simultaneously from each patient. CVP measurement difference (|CVP-mean - CVP-end|) was defined as the difference between CVP-mean and CVP-end. The ΔCVP was calculated as the difference between the peak (CVPmax) and the nadir value (CVPmin) during the respiratory cycle, which was automatically recorded on the monitor screen. Subjects with |CVP-mean - CVP-end|≥ 2 mmHg were divided into the inconsistent group, while subjects with |CVP-mean - CVP-end| < 2 mmHg were divided into the consistent group.Results ΔCVP was significantly higher in the inconsistent group [7.17(2.77) vs.5.24(2.18), P<0.001] than that in the consistent group. There was a significantly positive relationship between ΔCVP and |CVP-mean - CVP-end| (r=0.283, P <0.0001). Bland-Altman plot showed the bias was -0.61 mmHg with a wide 95% limit of agreement (-3.34, 2.10) of CVP-end and CVP-mean. The area under the receiver operating characteristic curves (AUC) of ΔCVP for predicting |CVP-mean - CVP-end| ≥ 2 mmHg was 0.709. With a high diagnostic specificity, using ΔCVP<3 to detect |CVP-mean - CVP-end| lower than 2mmHg (consistent measurement) resulted in a sensitivity of 22.37% and a specificity of 93.06%. Using ΔCVP>8 to detect |CVP-mean - CVP-end| >8 mmHg (inconsistent measurement) resulted in a sensitivity of 31.94% and a specificity of 91.32%.Conclusions CVP-end and CVP-mean have statistical discrepancies in specific clinical scenarios. ΔCVP during the respiratory period is related to the variation of the two CVP methods. A high ΔCVP indicates a poor agreement between these two methods, whereas a low ΔCVP indicates a good agreement between these two methods.
Subject(s)
Respiration , Humans , Central Venous Pressure , ROC CurveABSTRACT
Authentication of walnut oil (WO) is challenging due to the adulteration of high-linoleic acid vegetable oils (HLOs) with similar fatty acid composition. To allow the discrimination of WO adulteration, a rapid, sensitive and stable scanning method based on supercritical fluid chromatography quadrupole time-of-flight mass spectrometry (SFC-QTOF-MS) was established to profile 59 potential triacylglycerol (TAGs) in HLOs samples within 10 min. Limit of quantitation of the proposed method is 0.002 µg mL-1 and the relative standard deviations range from 0.7% to 12.0%. TAGs profiles of WO samples from various varieties, geography origins, ripeness, and processing methods were used to construct orthogonal partial least squares-discriminant analysis (OPLS-DA) and OPLS models that were highly accurate in both qualitative and quantitative prediction at adulteration levels as low as 5% (w/w). This study advances the TAGs analysis to characterize vegetable oils and holds promise as an efficient method for oil authentication.
Subject(s)
Juglans , Plant Oils , Plant Oils/chemistry , Linoleic Acid/analysis , Triglycerides/chemistry , Food Contamination/analysisABSTRACT
As various aptasensors are adopted in clinical diagnosis, the development of convenient multiple-target determination is a field of ever-increasing interests. Herein, a label-free and amplified electrochemiluminescence (ECL) sensing platform was constructed to detect multiple targets of hemin, glucose and thrombin (TB) using peroxydisulfate (S2O82-) solution, which was one of the most convenient and economical ECL systems. It was worth mentioning that the target-induced bi-enzyme cascade catalysis reaction was developed to increase the ECL response strongly of S2O82- solution due to the production of (1O2)2* from the inter-reaction between reactive oxygen species (ROS) and sulfate radical (SO4â¢-). Specifically, with the layer-by-layer assembly of multi-walled carbon nanotubes (MWCNTs), glucose oxidase (GOx) and gold nanoparticles (AuNPs) as the interface, the guanine-rich (G-rich) thrombin aptamer (TBA) was anchored for hemin (target 1) detection, due to the electrocatalysis of hemin/G-quadruplex as a horseradish peroxidase mimicking DNAzyme (HRP-DNAzyme) towards dissolved oxygen for ROS generation. Second, in the presence of glucose (target 2), the ECL intensity was improved because glucose was the substrate of the bi-enzyme cascade catalysis reaction. Third, when TB (target 3) was sequentially incubated based on the above-mentioned aptasensor, the bi-enzyme catalysis was inhibited to decrease the ECL signal, due to the steric hindrance effect of the TB protein. As a result, the aptasensor achieved the nanomolar detection for hemin (3.33 nM), the micromolar detection for glucose (0.33 µM) and the femtomolar detection for TB (3.33 fM), respectively.