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OBJECTIVE: To recommend precision dosing and improve therapeutic efficacy against invasive fungal disease, a physiologically based pharmacokinetic model (PBPK) of oral isavuconazole (ISA) was established and used to explore its disposition across populations in different physiological and pathological states. METHODS: Twenty-five pharmacokinetic (PK) studies of oral ISA were identified through a systematic search of PubMed. Concentration-time data were extracted using WebPlotDigitizer. Physiochemical parameters were obtained from published literature and DrugBank. Model development and simulation used the Simcyp population-based simulator, and visual predictive check and predictive error were used for the model evaluation. Probability of target attainment and the cumulative fraction of response analyses were performed for dose optimization. RESULTS: The developed PBPK model was successfully validated in different populations. Most predicted concentration-time points aligned with the observed data, with acceptable predictive errors for the critical parameters. We predicted the PK profiles and parameters of ISA in a population with severe hepatic impairment (HI), a population with obesity and paediatric patients aged 1 to less than 6 years old. The probability of target attainment and cumulative fraction of response analyses indicated that the population with severe HI should have half the maintenance dose. The population with obesity and population with severe HI should have a loading dose of 300 mg every 8 h for 2 days. For paediatric patients aged 1 to less than 6 years old, a weight-based dosing regimen (5.38 mg/kg) of ISA was suggested. CONCLUSION: The predicted value aligns with observations, suggesting ISA's potential predictability in PK profiles for other populations. The recommended dosing regimens increase our understanding of the use of ISA in special populations.
Subject(s)
Antifungal Agents , Nitriles , Pyridines , Triazoles , Humans , Triazoles/pharmacokinetics , Triazoles/administration & dosage , Antifungal Agents/pharmacokinetics , Antifungal Agents/administration & dosage , Nitriles/pharmacokinetics , Nitriles/administration & dosage , Pyridines/pharmacokinetics , Pyridines/administration & dosage , Administration, Oral , Child , Child, Preschool , Infant , Adult , Adolescent , Young Adult , Male , Middle Aged , Female , Aged , Invasive Fungal Infections/drug therapy , Models, BiologicalABSTRACT
Background: Research has indicated that VRK1 is essential for the tumor cell cycle. However, its prognostic and immunotherapeutic predictive significance has not been documented in hepatocellular carcinoma (HCC). Methods: The TCGA, ICGC, and GSE14520 datasets were used to investigate VRK1 expression and its predictive significance of survival outcomes. The qRT-PCR and immunohistochemistry (IHC) were used to confirm the findings. The immunotherapeutic response of VRK1 was anticipated by the IMvigor210 cohort. Lastly, the association between immune infiltration, m6A modification, and functional enrichment of differentially expressed genes (DEGs) was investigated in connection to VRK1 expression. Results: VRK1 expression was markedly elevated on both the mRNA and protein levels in HCC. In HCC patients, a high expression of VRK1 was linked to a poor prognosis. Furthermore, there was a substantial positive correlation seen between increased VRK1 expression and the response rate to anti-PD-L1 immunotherapy. Relationships between VRK1 and m6A-related genes as well as different immune cells were shown by correlation studies. Lastly, enrichment analysis revealed a tight relationship between VRK1 and important biological functions, including DNA replication, cell cycle control, and fatty acid metabolism. Conclusion: Our research reveals the potential of VRK1 as a novel biomarker for prognosis and immunotherapy response in HCC patients.
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Currently, numerous population pharmacokinetic (popPK) models for methotrexate (MTX) have been published for estimating PK parameters and variability. However, it is unclear whether the accuracy of these models is sufficient for clinical application. The aim of this study is to evaluate published models and assess their predictive performance according to the standards of scientific research. A total of 237 samples from 74 adult patients who underwent high-dose MTX (HDMTX) treatment at Shanghai Changzheng Hospital were collected. The software package NONMEM was used to perform an external evaluation for each model, including prediction-based diagnosis, simulation-based diagnosis, and Bayesian forecasting. The simulation-based diagnosis includes normalized prediction distribution error (NPDE) and visual predictive check (VPC). Following screening, 7 candidate models suitable for external validation were identified for comparison. However, none of these models exhibited excellent predictive performance. Bayesian simulation results indicated that the prediction precision and accuracy of all models significantly improved when incorporating prior concentration information. The published popPK models for MTX exhibit significant differences in their predictive performance, and none of the models were able to accurately predict MTX concentrations in our data set. Therefore, before adopting any model in clinical practice, extensive evaluation should be conducted.
Subject(s)
Hematologic Neoplasms , Methotrexate , Adult , Humans , Methotrexate/pharmacokinetics , Bayes Theorem , China/epidemiology , Forecasting , Hematologic Neoplasms/drug therapy , Models, BiologicalABSTRACT
Microtremor recording tests using an accelerometer were carried out in this paper with the aim of characterizing the effects of seasonally frozen soil on the seismic site response, including the two-direction microtremor spectrum, site predominant frequency, and site amplification factor. The study selected eight typical seasonal permafrost sites in China for site microtremor measurements during both summer and winter seasons. Based on the recorded data, the horizontal and vertical components of the microtremor spectrum, HVSR curves, site predominant frequency, and site amplification factor were calculated. The results showed that seasonally frozen soil increased the predominant frequency of the horizontal component of the microtremor spectrum, while the effect on the vertical component was less noticeable. It indicates that the frozen soil layer has a significant impact on the propagation path and energy dissipation of seismic waves in the horizontal direction. Furthermore, the peak values of the horizontal and vertical components of the microtremor spectrum decreased by 30% and 23%, respectively, due to the presence of seasonally frozen soil. The predominant frequency of the site increased by a maximum of 35% and a minimum of 2.8%, while the amplification factor decreased by a maximum of 38% and a minimum of 11%. Additionally, a relationship between the increased site predominant frequency and the cover thickness was proposed.
Subject(s)
Soil , China , Freezing , SeasonsABSTRACT
Human telomeres are linked to genetic instability and a higher risk of developing cancer. Therefore, to improve the dismal prognosis of pancreatic cancer patients, a thorough investigation of the association between telomere-related genes and pancreatic cancer is required. Combat from the R package "SVA" was performed to correct the batch effects between the TCGA-PAAD and GTEx datasets. After differentially expressed genes (DEGs) were assessed, we constructed a prognostic risk model through univariate Cox regression, LASSO-Cox regression, and multivariate Cox regression analysis. Data from the ICGC, GSE62452, GSE71729, and GSE78229 cohorts were used as test cohorts for validating the prognostic signature. The major impact of the signature on the tumor microenvironment and its response to immune checkpoint drugs was also evaluated. Finally, PAAD tissue microarrays were fabricated and immunohistochemistry was performed to explore the expression of this signature in clinical samples. After calculating 502 telomere-associated DEGs, we constructed a three-gene prognostic signature (DSG2, LDHA, and RACGAP1) that can be effectively applied to the prognostic classification of pancreatic cancer patients in multiple datasets, including TCGA, ICGC, GSE62452, GSE71729, and GSE78229 cohorts. In addition, we have screened a variety of tumor-sensitive drugs targeting this signature. Finally, we also found that protein levels of DSG2, LDHA, and RACGAP1 were upregulated in pancreatic cancer tissues compared to normal tissues by immunohistochemistry analysis. We established and validated a telomere gene-related prognostic signature for pancreatic cancer and confirmed the upregulation of DSG2, LDHA, and RACGAP1 expression in clinical samples, which may provide new ideas for individualized immunotherapy.
Subject(s)
Pancreatic Neoplasms , Humans , Prognosis , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/genetics , Telomere/genetics , Biomarkers , Tumor Microenvironment/genetics , Pancreatic NeoplasmsABSTRACT
AIMS: Patients with epilepsy often require long-term use of antiseizure medications (ASMs) to control their seizures. However, movement disorders (MDs) related to ASMs can significantly impact their quality of life. This study aims to analyse MDs related to ASMs in the Food and Drug Administration Adverse Event Reporting System database to provide recommendations for safe medication. METHODS: All adverse drug reactions associated with 26 marketed ASMs in Food and Drug Administration Adverse Event Reporting System were extracted for analysis. Disproportionality analyses were used to assess the association between ASMs and MDs, and signal colour scale maps were created to identify potential ASM-MD safety signals. RESULTS: A total of 1921 cases experienced MDs while taking ASMs were included. A higher prevalence of MDs was observed in females compared to males. The association between specific MDs with ASMs was revealed, including known and unknown MDs such as tremors, Parkinson and paralysis. Lamotrigine and carbamazepine exhibited multiple significant MDs, while levetiracetam and pregabalin were linked to the earlier onset of MDs. Generally, higher doses were linked to a higher incidence of MDs. CONCLUSION: MDs were the most obvious adverse drug reactions in the nervous system triggered by using ASMs. Fourteen drugs exhibited positive signals for MDs, including some not previously reported. Conversely, 12 ASMs were deemed to have a lower possibility of inducing MDs. The incidence of MDs can be mitigated by selecting appropriate ASMs for epileptic patients. These findings enhance our understanding of the relationship between ASMs and MDs.
Subject(s)
Drug-Related Side Effects and Adverse Reactions , Movement Disorders , United States , Female , Male , Humans , Quality of Life , United States Food and Drug Administration , Movement Disorders/epidemiology , Movement Disorders/etiology , Drug-Related Side Effects and Adverse Reactions/epidemiology , Drug-Related Side Effects and Adverse Reactions/etiology , Benzodiazepines , Anticonvulsants/adverse effectsABSTRACT
A population pharmacokinetic (pop PK) model of polymyxin B was developed using nonlinear mixed-effects (NONMEM) modeling based on free plasma concentrations to determine whether dose adjustment is required in critically ill patients. One thousand pharmacokinetic profiles for virtual patients with a body weight of 70 kg were simulated using Monte Carlo simulation at different dose scenarios, and area under the concentration-time curve of free drug (fAUC) was computed. The probability of target attainment (PTA) at each minimum inhibitory concentration (MIC) was calculated using fAUC/MIC as a pharmacokinetic/pharmacodynamic (PK/PD) index. The final population PK model was a 2-compartment model. PTA showed that 3.5 mg/kg/day regimens of polymyxin B effectively achieved the fAUC/MIC target of 10 (one log10 kill) against Pseudomonas aeruginosa strains with MIC of 1 mg/L or less (PTA, 90.7% or greater), while the dose regimen were ineffective against strains with an MIC of 2 mg/L or greater (PTA, 56.9% or less). For Klebsiella pneumoniae, the fAUC/MIC target of 17.4 (one log10 kill) was achieved in more than 90.4% of cases for MIC of 0.5 mg/L or less with 3 mg/kg/day regimens. However, the PTA decreased dramatically as MICs increased above 1 mg/L (PTA, 56.1% or less). The polymyxin B dosage regimen of 3.5 mg/kg/day and 3 mg/kg/day are sufficient to treat P. aeruginosa infections with an MIC of 1 mg/L or less and K. pneumoniae infections with an MIC of 0.5 mg/L or less, respectively. The current recommended dose (1.5-3 mg/kg/day) of polymyxin B appears inadequate to attain the PK/PD target for therapeutic efficacy against infections caused by P. aeruginosa and K. pneumoniae isolates when MIC is above the values.
Subject(s)
Anti-Bacterial Agents , Polymyxin B , Humans , Monte Carlo Method , Critical Illness , Computer Simulation , Microbial Sensitivity TestsABSTRACT
Background: Growing evidence suggests that infiltrating neutrophils are key players in hepatocellular carcinoma (HCC) tumor progression. However, a comprehensive analysis of the biological roles of neutrophil infiltration and related genes in clinical outcomes and immunotherapy is lacking. Methods: HCC samples were obtained from the TCGA and GEO databases. The CIBERSORT algorithm was used to reveal the TIME landscape. Gene modules significantly associated with neutrophils were found using weighted gene co-expression network analysis (WGCNA), a "dynamic tree-cut" algorithm, and Pearson correlation analysis. Genes were screened using Cox regression analysis and LASSO and prognostic value validation was performed using Kaplan-Meier curves and receiver operating characteristic (ROC) curves. Risk scores (RS) were calculated and nomograms were constructed incorporating clinical variables. Gene set variation analysis (GSVA) was used to calculate signaling pathway activity. Immunophenoscore (IPS) was used to analyze differences in immunotherapy among samples with different risk scores. Finally, the relationship between RS and drug sensitivity was explored using the pRRophetic algorithm. Results: 10530 genes in 424 samples (50 normal samples, 374 tumor samples) were obtained from the TCGA database. Using WGCNA, the "MEbrown" gene module was most associated with neutrophils. Nine genes with prognostic value in HCC (PDLIM3, KLF2, ROR2, PGF, EFNB1, PDZD4, PLN, PCDH17, DOK5) were finally screened. Prognostic nomograms based on RS, gender, tumor grade, clinical stage, T, N, and M stages were constructed. The nomogram performed well after calibration curve validation. There is an intrinsic link between risk score and TMB and TIME. Samples with different risk scores differed in different signaling pathway activity, immunopharmaceutical treatment and chemotherapy sensitivity. Conclusion: In conclusion, a comprehensive analysis of neutrophil-related prognostic features will help in prognostic prediction and advance individualized treatment.
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Background: With advances in early diagnosis and treatment, the number of cancer survivors continues to grow, and more and more cancer survivors face the threat of second primary cancer (SPM). Second primary pancreatic ductal adenocarcinoma (spPDAC) is an important subclass of SPM, but its prognostic characteristics are poorly understood. Methods: A total of 5,439 spPDAC samples and 67,262 primary pancreatic ductal adenocarcinoma (pPDAC) samples were extracted from the SEER database for this study. Survival differences between spPDAC and pPDAC samples were compared using Kaplan-Meier curves and log-rank tests. The Fine and Gray proportional subdistributed hazard method was used to analyze potential associations between clinical variables and pancreatic ductal adenocarcinoma-specific death (PDACSD) and death from other causes. After that, the clinical variables significantly related to PDACSD were screened out to construct a competing risk nomogram, which was used to evaluate the probability of the occurrence of PDACSD. The C-index was used to evaluate the discriminative ability of the model. The area under the curve (AUC) was used to verify the discrimination of the model. The calibration curve was used to verify the calibration of the model. Decision curve analysis (DCA) was used to validate the clinical utility of the model. Results: Compared with patients with spPDAC, the pPDAC sample had a better prognosis (p = 0.0017). Across all spPDAC samples, the three most common sites of first-present cancer were the prostate, breast, and digestive system. Age (p < 0.001), race (p = 0.006), interval (p = 0.016), location (p < 0.001), T stage (p = 0.003), M stage (p < 0.001), chemotherapy (p < 0.001), and radiotherapy (p = 0.006) were the clinical variables associated with PDACSD screened by multivariate competing risks analysis. The concordance index values for the training and validation sets were 0.665 (95% CI, 0.655, 0.675) and 0.666 (95% CI, 0.650, 0.682), respectively. AUC, calibration curve, and DCA indicated that the model we constructed had good discrimination, calibration, and clinical utility. Conclusions: In conclusion, we first analyzed the impact of previous cancer history on prognosis. We then constructed a competing risk model that can predict the probability of developing PDACSD in spPDAC. This model has good discriminative ability, calibration, and clinical practicability and has certain guiding value for clinical decision-making.
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Apoptosis is a critical event in the pathogenesis of lung ischemia/reperfusion (I/R) injury. Sirtuin 3 (SIRT3), an important deacetylase predominantly localized in mitochondria, regulates diverse physiological processes, including apoptosis. However, the detailed mechanisms by which SIRT3 regulates lung I/R injury remain unclear. Many polyphenols strongly regulate the sirtuin family. In this study, we found that a polyphenol compound, procyanidin B2 (PCB2), activated SIRT3 in mouse lungs. Due to this effect, PCB2 administration attenuated histological lesions, relieved pulmonary dysfunction, and improved the survival rate of the murine model of lung I/R injury. Additionally, this treatment inhibited hypoxia/reoxygenation (H/R)-induced A549 cell apoptosis and rescued Bcl-2 expression. Using Sirt3-knockout mice and specific SIRT3 knockdown in vitro, we further found that SIRT3 strongly protects against lung I/R injury. Sirt3 deficiency or enzymatic inactivation substantially aggravated lung I/R-induced pulmonary lesions, promoted apoptosis, and abolished PCB2-mediated protection. Mitochondrial pyruvate kinase M2 (PKM2) inhibits apoptosis by stabilizing Bcl-2. Here, we found that PKM2 accumulates and is hyperacetylated in mitochondria upon lung I/R injury. By screening the potential sites of PKM2 acetylation, we found that SIRT3 deacetylates the K433 residue of PKM2 in A549 cells. Transfection with a deacetylated mimic plasmid of PKM2 noticeably reduced apoptosis, while acetylated mimic transfection abolished the protective effect of PKM2. Furthermore, PKM2 knockdown or inhibition in vivo significantly abrogated the antiapoptotic effects of SIRT3 upregulation. Collectively, this study provides the first evidence that the SIRT3/PKM2 pathway is a protective target for the suppression of apoptosis in lung I/R injury. Moreover, this study identifies K433 deacetylation of PKM2 as a novel modification that regulates its anti-apoptotic activity. In addition, PCB2-mediated modulation of the SIRT3/PKM2 pathway may significantly protect against lung I/R injury, suggesting a novel prophylactic strategy for lung I/R injury.
Subject(s)
Biflavonoids , Catechin , Ischemia , Leukemia, Myeloid, Acute , Lung , Proanthocyanidins , Reperfusion Injury , Sirtuin 3 , Animals , Biflavonoids/pharmacology , Catechin/pharmacology , Ischemia/metabolism , Leukemia, Myeloid, Acute/metabolism , Lung/blood supply , Lung/metabolism , Mice , Mitochondria/drug effects , Mitochondria/metabolism , Proanthocyanidins/pharmacology , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Pyruvate Kinase/genetics , Pyruvate Kinase/metabolism , Reperfusion Injury/drug therapy , Reperfusion Injury/genetics , Reperfusion Injury/metabolism , Sirtuin 3/genetics , Sirtuin 3/metabolism , Up-Regulation/drug effectsABSTRACT
The vivid iridescent response from particular butterflies is as an excellent example of how micro-engineered hierarchical architectures that combine physical structures and pigmentary inclusions create unique colouration. To date, however, detailed knowledge is missing to replicate such sophisticated structures in a robust, reliable manner. Here, we deliver spheres-in-grating assemblies with colouration effects as found in nature, exploiting embossed polymer gratings and self-assembled light-absorbing micro-spheres.
Subject(s)
Butterflies , Animals , Butterflies/chemistry , PigmentationABSTRACT
How an estuary responds to sea level rise (SLR) is complex and depends on energy drivers (e.g., tides and river inflows), estuarine geometry (e.g., length and depth), intrinsic fluid properties (e.g., density), and bed/bank roughness. While changes to the tidal range under SLR can impact estuarine sediment transport, water quality, and vegetation communities, studies on the altered tidal range under SLR are often based on case studies with outcomes applicable to a specific site. As such, this study produced a large ensemble of estuarine hydrodynamic models (>1800) to provide a systematic understanding of how tidal range dynamics within different estuary types may change under various SLR and river inflow scenarios. The results indicated that SLR often amplifies the tidal range of different estuary types, except for short estuaries with a low tidal range at the mouth where SLR attenuates the tides. SLR alters the location of the points with minimum tidal range and overall tidal range patterns in an estuary. Variations in tidal range were more evident in converging estuaries, shallower systems, or in estuaries with strong river inflows. These findings provide an indication of how different estuary types may respond to estuaries and may assist estuarine managers and decision makers.
Subject(s)
Estuaries/classification , Sea Level Rise/statistics & numerical data , Hydrodynamics , Models, Theoretical , Rivers , Water Quality , WetlandsABSTRACT
BACKGROUND: Treating perihilar cholangiocarcinoma (PHCC) is particularly difficult due to the fact that it is usually in an advanced stage at the time of diagnosis. Irreversible electroporation treatment (IRE) involves the local administration of a high-voltage electric current to target lesions without causing damage to surrounding structures. This study investigated the safety and efficacy of using IRE in conjunction with intraoperative biliary stent placement in cases of unresectable PHCC. METHODS: This study enrolled 17 patients with unresectable Bismuth type III/IV PHCC who underwent IRE in conjunction with intraoperative biliary stent placement (laparotomic) in two medical centers in Asia between June 2015 and July 2018. Analysis focused on the perioperative clinical course, the efficacy of biliary decompression, and outcomes (survival). RESULTS: Mean total serum bilirubin levels (mg/dL) on postoperative day (POD) 7, POD30, and POD90 were significantly lower than before IRE (respectively 3.46 vs 4.54, p=0.007; 1.21 vs 4.54, p<0.001; 1.99 vs 4.54, p<0.001). Mean serum carbohydrate antigen 19-9 (CA19-9, U/ml) levels were significantly higher on POD3 than before the operation (518.8 vs 372.4, p=0.001) and significantly lower on POD30 and POD90 (respectively 113.7 vs 372.4, p<0.001; 63.9 vs 372.4, p<0.001). No cases of Clavien-Dindo grade III/IV adverse events or mortality occurred within 90 days post-op. The median progression-free survival was 21.5 months, and the median overall survival was 27.9 months. All individuals who survived for at least one year did so without the need to carry percutaneous biliary drainage (PTBD) tubes. CONCLUSIONS: It appears that IRE treatment in conjunction with intraoperative biliary stent placement is a safe and effective approach to treating unresectable PHCC. The decompression of biliary obstruction without the need for PTBD tubes is also expected to improve the quality of life of patients.
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Background: Pancreatic cancer (PC) is one of the most lethal types of cancer with extremely poor diagnosis and prognosis, and the tumor microenvironment plays a pivotal role during PC progression. Poor prognosis is closely associated with the unsatisfactory results of currently available treatments, which are largely due to the unique pancreatic tumor microenvironment (TME). Methods: In this study, a total of 177 patients with PC from The Cancer Genome Atlas (TCGA) cohort and 65 patients with PC from the GSE62452 cohort in Gene Expression Omnibus (GEO) were included. Based on the proportions of 22 types of infiltrated immune cell subpopulations calculated by cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT), the TME was classified by K-means clustering and differentially expressed genes (DEGs) were determined. A combination of the elbow method and the gap statistic was used to explore the likely number of distinct clusters in the data. The ConsensusClusterPlus package was utilized to identify radiomics clusters, and the samples were divided into two subtypes. Result: Survival analysis showed that the patients with TMEscore-high phenotype had better prognosis. In addition, the TMEscore-high had better inhibitory effect on the immune checkpoint. A total of 10 miRNAs, 311 DEGs, and 68 methylation sites related to survival were obtained, which could be biomarkers to evaluate the prognosis of patients with pancreatic cancer. Conclusions: Therefore, a comprehensive description of TME characteristics of pancreatic cancer can help explain the response of pancreatic cancer to immunotherapy and provide a new strategy for cancer treatment.
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The inspection of electrical and mechanical (E&M) devices using unmanned aerial vehicles (UAVs) has become an increasingly popular choice in the last decade due to their flexibility and mobility. UAVs have the potential to reduce human involvement in visual inspection tasks, which could increase efficiency and reduce risks. This paper presents a UAV system for autonomously performing E&M device inspection. The proposed system relies on learning-based detection for perception, multi-sensor fusion for localization, and path planning for fully autonomous inspection. The perception method utilizes semantic and spatial information generated by a 2-D object detector. The information is then fused with depth measurements for object state estimation. No prior knowledge about the location and category of the target device is needed. The system design is validated by flight experiments using a quadrotor platform. The result shows that the proposed UAV system enables the inspection mission autonomously and ensures a stable and collision-free flight.
ABSTRACT
With the excellent structural design, rotary triboelectric nanogenerator (R-TENG) is suitable for harvesting mechanical energy such as wind energy and water energy to build a self-powered electrochemical system for environmental science. The electrochemical performance has been greatly improved by using the pulsed direct-current (PDC) output of a TENG; however, a full-wave PDC (FW-PDC) is hardly realized in R-TENG devices due to existence of phase superposition. Here, a R-TENG with FW-PDC output is reported to perform a self-powered electro-Fenton system for enhancing the removal efficiency of levofloxacin (OFL). By adjusting the rotation center angle ratio between each rotator and stator unit, the phase superposition of R-TENG caused by multiple parallel electrodes can be effectively eliminated, thus achieving the desired FW-PDC output. Because of the reduced electrode passivation effect, the removal efficiency of OFL is improved by 30% under equal electric charges through using the designed R-TENG with FW-PDC output compared to traditional R-TENG. This study provides a promising methodology to improve the performance of self-powered electrochemical process for treating environment pollutions.
Subject(s)
Electric Power Supplies , Nanotechnology , Electricity , Electrodes , LevofloxacinABSTRACT
Peptides derived from crimson snapper scales (CSSPs) were reported to possess excellent free radical scavenging activities in vitro. In present study, the anti-aging and anti-oxidative stress effects of CSSPs were evaluated in Drosophila melanogaster models. Results showed that the addition of CSSPs in the diets of normal Drosophila could effectively extend their lifespan and improve the motor ability of aged Drosophila. Moreover, CSSPs could protect Drosophila from oxidative damage induced by H2O2, paraquat and UV irradiation. The extension of lifespan was found to be associated with the effects of CSSPs in improving the antioxidant defense system of Drosophila, manifesting as the reduction of oxidation products MDA and PCO, the elevated activities of T-SOD, CAT and GSH-Px, and the upregulated expression of antioxidant related genes after CSSPs supplemented. Furthermore, CSSPs at 6 mg/mL significantly downregulated mTOR signaling pathway and activated autophagy in aged male Drosophila, and the inhibition on mTOR activation was probably mediated by the antioxidant effects of CSSPs. Our findings suggest that CSSPs have the potential in making dietary supplements against natural aging and oxidative stress in organisms.
Subject(s)
Animal Scales/chemistry , Antioxidants/pharmacology , Drosophila melanogaster/drug effects , Oxidative Stress/drug effects , Peptides/pharmacology , Animals , Autophagy/drug effects , Drosophila melanogaster/radiation effects , Female , Fishes , Hydrogen Peroxide/toxicity , Locomotion/drug effects , Longevity/drug effects , Male , Oxidative Stress/radiation effects , Paraquat/toxicity , Signal Transduction/drug effects , Ultraviolet RaysABSTRACT
A magnetic molecularly imprinted silica solid was obtained by sol-gel polymerization for the separation of domoic acid. The solid showed rapid adsorption kinetics with an adsorption equilibrium time of 5 min. The solid showed affinity to domoic acid under the interference of tryptophan and could be repeatedly used for 5 times at least. The solid was used as a solid-phase-extraction sorbent for the extraction of domoic acid from clam samples before measurement with liquid chromatography. The detection limit of 0.20 mg kg-1 was lower than the allowable limits in several countries or areas. The recoveries in the spiked samples were 88% approximately.
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In the last decade, an emerging three-dimensional (3D) printing technique named freeform 3D printing has revolutionized the biomedical engineering field by allowing soft matters with or without cells to be printed and solidified with high precision regardless of their poor self-supportability. The key to this freeform 3D printing technology is the supporting matrices that hold the printed soft ink materials during omnidirectional writing and solidification. This approach not only overcomes structural design restrictions of conventional layer-by-layer printing but also helps to realize 3D printing of low-viscosity or slow-curing materials. This article focuses on the recent developments in freeform 3D printing of soft matters such as hydrogels, cells, and silicone elastomers, for biomedical engineering. Herein, we classify the reported freeform 3D printing systems into positive, negative, and functional based on the fabrication process, and discuss the rheological requirements of the supporting matrix in accordance with the rheological behavior of counterpart inks, aiming to guide development and evaluation of new freeform printing systems. We also provide a brief overview of various material systems used as supporting matrices for freeform 3D printing systems and explore the potential applications of freeform 3D printing systems in different areas of biomedical engineering.
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Additive manufacturing (AM) of biomaterials has evolved from a rapid prototyping tool into a viable approach for the manufacturing of patient-specific implants over the past decade. It can tailor to the unique physiological and anatomical criteria of the patient's organs or bones through precise controlling of the structure during the 3D printing. Silicone elastomers, which is a major group of materials in many biomedical implants, have low viscosities and can be printed with a special AM platform, known as freeform 3D printing systems. The freeform 3D printing systems are composed of a supporting bath and a printing material. Current supporting matrices that are either commercially purchased or synthesized were usually disposed of after retrieval of the printed part. In this work, we proposed a new and improved supporting matrix comprises of synthesized calcium alginate microgels produced via encapsulation which can be recycled, reused, and recovered for multiple prints, hence minimizing wastage and cost of materials. The dehydration tolerance of the calcium alginate microgels was improved through physical means by the addition of glycerol and chemical means by developing new calcium alginate microgels encapsulated with glycerol. The recyclability of the heated calcium alginate microgels was also enhanced by a rehydration step with sodium chloride solution and a recovery step with calcium chloride solution via the ion exchange process. We envisaged that our reusable and recyclable biocompatible calcium alginate microgels can save material costs, time, and can be applied in various freeform 3D printing systems.