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1.
Food Chem X ; 22: 101467, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38872719

ABSTRACT

This study was based on QuEChERS cleanup coupled with UHPLC-MS/MS for the determination of γ-oryzanol compounds in vegetable oils. Several parameters of QuEChERS and UHPLC-MS/MS were studied for purification and detection of γ-oryzanol compounds in oil samples. Under the optimized conditions, the whole pretreatment procedure could be accomplished within 10 min without tedious procedure, larger volume of organic solvent and complicated apparatus. The limit of detections and the limit of quantifications for γ-oryzanol compounds were ranging from 0.1-0.3 µg kg-1 and 0.4-1.0 µg kg-1, respectively. Satisfactory recoveries of all analyts were ranging from 72.2 % to 101.3 %, and the intra-day and inter-day precision were less than 10.6 %. The validation indicated that rice band oil and corn oil were rich in 24-mCAF, CAF, ß-SIF, CMF and STF. The QuEChERS-UHPLC-MS/MS simultaneously quantified five γ-oryzanol compounds in lipid matrices and assessed the nutritional and functional substances of vegetable oils.

2.
J Cogn Neurosci ; 36(8): 1695-1714, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38579269

ABSTRACT

The brain is a hierarchical modular organization that varies across functional states. Network configuration can better reveal network organization patterns. However, the multi-hierarchy network configuration remains unknown. Here, we propose an eigenmodal decomposition approach to detect modules at multi-hierarchy, which can identify higher-layer potential submodules and is consistent with the brain hierarchical structure. We defined three metrics: node configuration matrix, combinability, and separability. Node configuration matrix represents network configuration changes between layers. Separability reflects network configuration from global to local, whereas combinability shows network configuration from local to global. First, we created a random network to verify the feasibility of the method. Results show that separability of real networks is larger than that of random networks, whereas combinability is smaller than random networks. Then, we analyzed a large data set incorporating fMRI data from resting and seven distinct tasking conditions. Experiment results demonstrates the high similarity in node configuration matrices for different task conditions, whereas the tasking states have less separability and greater combinability between modules compared with the resting state. Furthermore, the ability of brain network configuration can predict brain states and cognition performance. Crucially, derived from tasks are highlighted with greater power than resting, showing that task-induced attributes have a greater ability to reveal individual differences. Together, our study provides novel perspectives for analyzing the organization structure of complex brain networks at multi-hierarchy, gives new insights to further unravel the working mechanisms of the brain, and adds new evidence for tasking states to better characterize and predict behavioral traits.


Subject(s)
Brain , Magnetic Resonance Imaging , Nerve Net , Humans , Brain/physiology , Brain/diagnostic imaging , Adult , Male , Nerve Net/physiology , Nerve Net/diagnostic imaging , Female , Young Adult , Brain Mapping , Connectome , Psychomotor Performance/physiology
3.
Int J Biol Macromol ; 268(Pt 2): 131736, 2024 May.
Article in English | MEDLINE | ID: mdl-38653433

ABSTRACT

A novel cationic lipoic acid grafted low molecular weight chitosan (LCNE-LA) conjugate was constructed and further self-assembled into GSH-responsive cationic nanocarrier to achieve better antitumor effect by combining encapsulated chemotherapy and oxidative damage induced by ROS. The resultant LCNE-LA cationic micelle exhibited favorable physicochemical properties (low CMC, small size, positively zeta potential and good stability), excellent biosafety and desired redox sensitivity. Next, doxorubicin (Dox) was embedded into hydrophobic core to form stable Dox/LCNE-LA micelle that had superior loading capacity. The GSH-induced release behavior, cellular uptake ability, ROS generation and GSH consumption capacity and in vitro antitumor activity of Dox/LCNE-LA micelle were systematically evaluated. Consequently, Dox/LCNE-LA cationic micelle with positively charged could efficiently enter into cancer cell and redox-sensitive release Dox via disulfide-thiol exchange reaction, which usually expend abundant GSH and disrupt redox homeostasis. Studies further confirmed that Dox/LCNE-LA micelle could increase ROS and reduced GSH content which might cause oxidative damage to tumor cell. Antitumor activity indicated that Dox/LCNE-LA micelle achieved an excellent cancer-killing effect, which might be attributed to combination treatment of Dox and ROS induce oxidative damage. Overall, this research was expected to provide a platform for antitumor treatment by triggering Dox release and promoting ROS generation.


Subject(s)
Antineoplastic Agents , Chitosan , Doxorubicin , Glutathione , Micelles , Molecular Weight , Oxidative Stress , Chitosan/chemistry , Chitosan/pharmacology , Doxorubicin/pharmacology , Doxorubicin/chemistry , Glutathione/metabolism , Humans , Oxidative Stress/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Cations/chemistry , Drug Carriers/chemistry , Reactive Oxygen Species/metabolism , Drug Liberation , Cell Line, Tumor
4.
Water Res ; 254: 121410, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38471200

ABSTRACT

Packed fixed-bed reactors are traditionally used for heterogeneous catalytic ozonation. However, a high solid-to-liquid requirement, poor ozone dissolution, ineffective utilization of catalyst surface area, and production of large amounts of catalyst waste impede application of such reactors. In this study, we designed a suspension catalytic ozonation reactor and compared the performance of this reactor with that of a traditional fixed-bed catalytic ozonation reactor employing oxalic acid (OA) as the target contaminant. Our results showed that total O3 dissolved into the suspension reactor (117-134 mg.L-1) was much higher compared to that measured in the fixed-bed reactor (53 mg.L-1) due to a higher O3(g) interphase mass transfer rate in the suspension reactor. In accordance with the higher O3(g) interphase mass transfer, we observed a much higher proportional OA removal (32 %) compared to that achieved in the fixed-bed reactor (10%) employing an Fe-oxide catalyst supported on Al2O3 (Fe-oxide@Al2O3) in both reactors. Use of a double-layered Cu-Al hydroxide (Cu-Al LDHs) catalyst in the suspension reactor further enhanced the performance with nearly 90 % OA removal observed. Given the superior performance of the suspension reactor, we investigated the impact of operating conditions (catalyst dosage, hydraulic retention time and ozone dosage) employing Cu-Al LDHs as the catalyst. We also developed a mathematical kinetic model to describe the performance of the suspension reactor and, through use of the kinetic model, showed that O3(g) interphase transfer rate was the rate-limiting step in OA removal. Thus, improvement in ozone gas diffuser design is required to improve the performance of the suspension reactor. Overall, the present study demonstrated that suspension reactors were more effective than fixed-bed reactors for oxidation of surface-active organic compounds such as OA due to the higher ozone interphase mass transfer rate and effective utilization of the catalyst surface area that can be achieved. As such, further research on suspension reactor design and development of catalysts suitable for use in suspension reactors should facilitate large-scale application of catalytic ozonation processes by the wastewater treatment industry.


Subject(s)
Ozone , Water Pollutants, Chemical , Water Purification , Water Purification/methods , Oxides , Oxidation-Reduction , Models, Theoretical , Catalysis , Oxalic Acid , Water Pollutants, Chemical/analysis
5.
Front Neurosci ; 18: 1303741, 2024.
Article in English | MEDLINE | ID: mdl-38525375

ABSTRACT

Brain network analysis provides essential insights into the diagnosis of brain disease. Integrating multiple neuroimaging modalities has been demonstrated to be more effective than using a single modality for brain network analysis. However, a majority of existing brain network analysis methods based on multiple modalities often overlook both complementary information and unique characteristics from various modalities. To tackle this issue, we propose the Beta-Informativeness-Diffusion Multilayer Graph Embedding (BID-MGE) method. The proposed method seamlessly integrates structural connectivity (SC) and functional connectivity (FC) to learn more comprehensive information for diagnosing neuropsychiatric disorders. Specifically, a novel beta distribution mapping function (beta mapping) is utilized to increase vital information and weaken insignificant connections. The refined information helps the diffusion process concentrate on crucial brain regions to capture more discriminative features. To maximize the preservation of the unique characteristics of each modality, we design an optimal scale multilayer brain network, the inter-layer connections of which depend on node informativeness. Then, a multilayer informativeness diffusion is proposed to capture complementary information and unique characteristics from various modalities and generate node representations by incorporating the features of each node with those of their connected nodes. Finally, the node representations are reconfigured using principal component analysis (PCA), and cosine distances are calculated with reference to multiple templates for statistical analysis and classification. We implement the proposed method for brain network analysis of neuropsychiatric disorders. The results indicate that our method effectively identifies crucial brain regions associated with diseases, providing valuable insights into the pathology of the disease, and surpasses other advanced methods in classification performance.

6.
J Integr Plant Biol ; 66(4): 638-641, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38351739

ABSTRACT

The compact CRISPR/CasΦ2 system provides a complementary genome engineering tool for efficient gene editing including cytosine and adenosine base editing in wheat and rye with high specificity, efficient use of the protospacer-adjacent motif TTN, and an alternative base-editing window.


Subject(s)
Gene Editing , Triticum , Triticum/genetics , CRISPR-Cas Systems/genetics , Secale/genetics , Clustered Regularly Interspaced Short Palindromic Repeats
7.
Int J Endocrinol ; 2024: 9294113, 2024.
Article in English | MEDLINE | ID: mdl-38379936

ABSTRACT

Purpose: Type 2 diabetes mellitus is considered as one of the risk factors for cognitive impairment. DPP4 inhibitors are effective drugs for the treatment of type 2 diabetes mellitus. However, the relationship between DPP4 inhibitors and cognitive dysfunction remains unclear. Therefore, we used a meta-analysis to determine the association between DPP4 inhibitors and cognitive impairment in type 2 diabetes mellitus. Methods: We systematically searched PubMed, CNKI, and the Cochrane Library at the time of establishment, 2022, and then made inclusion criteria and screened strategies to identify studies with more precise correlations. Results: We included 10 studies with 5,583 participants. The data showed that DPP4 inhibitors significantly reduced the incidence rate of cognitive impairment in type 2 diabetes mellitus (SMD: 0.99; 95% CI [0.59, 1.38]). Furthermore, there was a linear correlation found between cognitive impairment in type 2 diabetes mellitus and fasting blood glucose, 2-hour postprandial blood glucose, and glycosylated hemoglobin. DPP4 inhibitors decreased fasting blood glucose (FPG) (SMD: 0.52; 95% CI [-0.68, -0.37]), blood glucose (2hPPG) at 2 hours after the meal (SMD: 0.82; 95% CI, [-1.2, -0.43]), and HbA1c (SMD: 0.34; 95% CI [-0.48, -0.21]). All data were statistically significant (P < 0.0001). Furthermore, we conducted subgroup analyses of the following measures at various treatment durations and ages: cognitive scores, fasting blood glucose, glycosylated hemoglobin, and two-hour postprandial blood glucose. Conclusion: DPP4 inhibitors significantly improved type 2 diabetic mellitus individuals' cognitive impairment and reduced fasting blood glucose, 2-hour postprandial blood glucose, and glycosylated hemoglobin. Subgroup analysis showed that people aged 60 to 70 years had better treatment effects at 0-180 days. This trial is registered with CRD42023399473.

8.
Int J Mol Sci ; 25(2)2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38255945

ABSTRACT

The determination of the soybean branch number plays a pivotal role in plant morphogenesis and yield components. This polygenic trait is subject to environmental influences, and despite its significance, the genetic mechanisms governing the soybean branching number remain incompletely understood. To unravel these mechanisms, we conducted a comprehensive investigation employing a genome-wide association study (GWAS) and bulked sample analysis (BSA). The GWAS revealed 18 SNPs associated with the soybean branch number, among which qGBN3 on chromosome 2 emerged as a consistently detected locus across two years, utilizing different models. In parallel, a BSA was executed using an F2 population derived from contrasting cultivars, Wandou35 (low branching number) and Ruidou1 (high branching number). The BSA results pinpointed a significant quantitative trait locus (QTL), designated as qBBN1, located on chromosome 2 by four distinct methods. Importantly, both the GWAS and BSA methods concurred in co-locating qGBN3 and qBBN1. In the co-located region, 15 candidate genes were identified. Through gene annotation and RT-qPCR analysis, we predicted that Glyma.02G125200 and Glyma.02G125600 are candidate genes regulating the soybean branch number. These findings significantly enhance our comprehension of the genetic intricacies regulating the branch number in soybeans, offering promising candidate genes and materials for subsequent investigations aimed at augmenting the soybean yield. This research represents a crucial step toward unlocking the full potential of soybean cultivation through targeted genetic interventions.


Subject(s)
Genome-Wide Association Study , Glycine max , Humans , Glycine max/genetics , Chromosomes, Human, Pair 2 , Genetic Engineering , Molecular Sequence Annotation
9.
Cardiovasc Ther ; 2023: 7611819, 2023.
Article in English | MEDLINE | ID: mdl-38125703

ABSTRACT

Objective: To investigate the association between ß1 adrenergic receptor autoantibodies (ß1-AA) and angiotensin II type-1 receptor autoantibodies (AT1-AA) and cardiac function in patients with hypertension complicated with left ventricular diastolic function limitation. Methods: A total of 120 patients with essential hypertension who were not taking drug treatment and were hospitalised in the Department of Cardiology at the authors' hospital from April 2018 to December 2018 were enrolled in this study and divided into a diastolic dysfunction group (65 cases) and a normal diastolic group (55 cases) according to their left ventricular diastolic function. The levels of cardiac parameters, ß1-AA, AT1-AA, and other indicators were compared. Logistic regression analysis was used to analyse the related factors affecting left ventricular diastolic dysfunction (LVDD). The diagnostic efficacy of related factors in the diagnosis of diastolic dysfunction was evaluated. Results: Univariate analysis demonstrated that the left ventricular posterior wall diameter (10.29 ± 1.23 vs. 9.12 ± 1.53), left ventricular systolic dysfunction (10.56 ± 1.37 vs. 9.43 ± 1.44), systolic blood pressure (152.37 ± 10.24 vs. 140.33 ± 5.99), diastolic blood pressure (95.66 ± 6.34 vs. 87.33 ± 7.28), ß1-AA (33 vs. 9 cases), and AT1-AA (35 cases vs. 12 cases) were higher in the dysfunction group than in the control group (all P < 0.05). Multivariate regression analysis showed that ß1-AA (odds ratio (OR) = 1.96, 95% confidence interval (CI): 1.369-4.345) and AT1-AA (OR = 2.02, 95% CI: 1.332-6.720) were independent risk factors for cardiac diastolic dysfunction (P < 0.05). Both autoimmune antibodies had a certain predictive value, and the combined prediction value of the two was the highest, with an area under the curve of 0.942 (95% CI: 0.881~0.985). Conclusion: The positive rate of ß1-AA and AT1-AA in essential hypertension patients with LVDD was higher than that in the normal group. Both ß1-AA and AT1-AA could be used as early markers of LVDD in essential hypertension patients.


Subject(s)
Cardiomyopathies , Hypertension , Ventricular Dysfunction, Left , Humans , Autoantibodies , Hypertension/complications , Hypertension/diagnosis , Hypertension/drug therapy , Ventricular Function, Left , Ventricular Dysfunction, Left/diagnosis , Cardiomyopathies/complications , Essential Hypertension/complications , Essential Hypertension/diagnosis
10.
Molecules ; 28(15)2023 Jul 28.
Article in English | MEDLINE | ID: mdl-37570706

ABSTRACT

The development of efficient electrocatalysts for hydrogen evolution reactions is an extremely important area for the development of green and clean energy. In this work, a precursor material was successfully prepared via electrodeposition of two doping elements to construct a co-doped cobalt hydroxide electrocatalyst (Ru-Co(OH)2-Se). This approach was demonstrated to be an effective way to improve the performance of the hydrogen evolution reaction (HER). The experimental results show that the material exhibited a smaller impedance value and a larger electrochemically active surface area. In the HER process, the overpotential was only 109 mV at a current density of 10 mA/cm2. In addition, the doping of selenium and ruthenium effectively prevented the corrosion of the catalysts, with the (Ru-Co(OH)2-Se) material showing no significant reduction in the catalytic performance after 50 h. This synergistic approach through elemental co-doping demonstrated good results in the HER process.

11.
Int J Biol Macromol ; 247: 125849, 2023 Aug 30.
Article in English | MEDLINE | ID: mdl-37460070

ABSTRACT

Amphiphilic low molecular weight chitosan-lipoic acid (LC-LA) conjugates with different degrees of substitution (DS) of LA were synthesized by N, N'­carbonyldiimidazole (CDI) catalysis to self-assemble into redox-sensitive micelles. Critical micelle concentration (CMC), size, zeta potential, biocompatibility and redox-sensitive behavior of blank micelles were investigated. The results indicated that blank micelles with low CMC, nanoscale size and positive zeta potential showed excellent biocompatibility and redox-sensitive behavior. Doxorubicin (Dox) loaded micelles were prepared by encapsulating Dox into blank micelles. The loading ability, trigger-release behavior, antitumor activity and cellular uptake of Dox loaded micelles were studied. The results demonstrated that Dox loaded micelles with superior loading ability exhibited redox-trigger behavior, strong antitumor activity and increased cellular uptake efficiency against A549 cell. Besides, the effect of DS of LA on above properties was estimated. An increase in DS of LA reduced the CMC and cumulative release amount of Dox, but improved the loading efficiency, antitumor activity, and cellular uptake of Dox loaded micelles, which resulted from stronger interaction of hydrophobic groups in micelles with the DS of LA increased. Overall, self-assembled LC-LA micelles with good biosecurity and redox-sensitive behavior hold promising application prospects in Dox delivery and improving cancer therapeutic effect of Dox.


Subject(s)
Chitosan , Thioctic Acid , Micelles , Chitosan/chemistry , Thioctic Acid/chemistry , Drug Carriers/chemistry , Molecular Weight , Doxorubicin/pharmacology , Doxorubicin/chemistry , Oxidation-Reduction , Drug Delivery Systems/methods , Hydrogen-Ion Concentration
12.
Food Chem ; 429: 136886, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37499506

ABSTRACT

New amphiphilic low molecular weight chitosan-graft-nicotinic acid bearing decyl groups (LCND) was synthesized by two-step reaction and spontaneously assembled into cationic micelle by ultra-sonication method to improve water solubility and photostability properties of α-tocopherol. The chemical structure of LCND was characterized and physical properties of cationic micelle were evaluated. Results displayed that cationic micelle exhibited strong self-assemble ability with nanoscale spherical morphology and showed best loading ability with loading content of 18.50% when the feeding ratio of LCND to α-tocopherol reached 10:3. Meanwhile, the greatly enhanced water solubility, photostability and sustained release behavior of α-tocopherol in cationic micelle were observed. The cumulative release of α-tocopherol in cationic micelle reached up 82.18% within 96 h while free α-tocopherol was completely released within 10 h. Additionally, release kinetics models were also fitted. The LCND cationic micelle could be promising nanocarrier for improving the physicochemical properties of α-tocopherol in food fields.


Subject(s)
Chitosan , Micelles , alpha-Tocopherol/chemistry , Solubility , Chitosan/chemistry , Delayed-Action Preparations , Molecular Weight , Drug Carriers/chemistry , Water/chemistry , Particle Size
13.
Pediatr Blood Cancer ; : e30382, 2023 Jun 07.
Article in English | MEDLINE | ID: mdl-37283279

ABSTRACT

OBJECTIVE: To analyze the prognostic factors of sepsis in children with acute leukemia admitted to the pediatric intensive care unit (PICU) and to compare the efficacy of different scoring systems for predicting the outcome of children. METHODS: Patients with an acute leukemia diagnosis admitted to a tertiary care university hospital PICU due to sepsis during chemotherapy between May 2015 and August 2022 were retrospectively analyzed through an electronic medical record system. RESULTS: During this period, 693 children with acute leukemia initially diagnosed were admitted to the center, and 155 (22.3%) of them were transferred to PICU due to deterioration of the disease during treatment. Total 109 (70.3%) patients were transferred to PICU due to sepsis. Here, 17 patients was excluded (prior treatment from another hospital; referring from other hospitals; discontinued treatment; incomplete medical record). Of the 92 patients studied, the mortality rate was 35.9%. Multivariate analysis revealed that remission status, lactate level, invasive mechanical ventilation (IMV), and inotropic support within 48 hours after PICU transfer were independent risk factors for PICU mortality. The pediatric sequential organ failure assessment (PSOFA) score had the greatest predictive validity for hospital mortality (area under the receiver operating characteristic curve [AUROC]: 0.83, 95% confidence intervals [CI]: 0.74-0.92), followed by the pediatric early warning score (PEWS) (0.82, 0.73-0.91) and pediatric critical illness score (PCIS) (0.79, 0.69-0.88). CONCLUSION: The mortality rate among children with acute leukemia complicated with sepsis is high after being transferred to the PICU. Various scoring systems can be used to monitor the clinical status of patients, identify sepsis early, detect critical illness, and determine the optimal time for transfer to the PICU for supportive treatment, thereby improving the prognosis of these patients.

14.
Front Cardiovasc Med ; 10: 984572, 2023.
Article in English | MEDLINE | ID: mdl-36873392

ABSTRACT

A-41-year-old man diagnosed with acute myeloid leukemia (AML) survived dasatinib + fluconazole drug-induced long QT syndrome, sudden cardiac arrest, and torsade de pointes. Drug features and interaction jointly contributed to the whole process. Therefore, appropriate attention to drug interaction and close ECG monitoring are highly recommended for hospitalized patients, especially for those undergoing multi-drug regimens.

15.
Angew Chem Int Ed Engl ; 62(15): e202300159, 2023 Apr 03.
Article in English | MEDLINE | ID: mdl-36762878

ABSTRACT

Despite the significance of sultines in synthesis, medicine, and materials science, the chemistry of sultines has remained unexplored due to their inaccessibility. Herein, we demonstrate the development of a photoredox-catalyzed multifluoromethyl radical addition/SO2 incorporation/polar cyclization cascade approach to multifluoromethylated γ-sultines. The reactions proceed by single electron transfer induced multifluoromethyl radical addition to an alkene followed by SO2 incorporation, and single-electron reduction for polar 5-exo-tet cyclization. Key to the success of the protocol is the use of easily oxidizable multifluoroalkanesulfinates as bifunctional reagents. The reactions proceed with excellent functional-group tolerance to deliver γ-sultines in moderate to excellent yields.

16.
Front Comput Neurosci ; 17: 1109371, 2023.
Article in English | MEDLINE | ID: mdl-36817319

ABSTRACT

Meltblown nonwoven materials have gained attention due to their excellent filtration performance. The research on the performance of the intercalation meltblown preparation process is complex and a current research focus in the field of chemical production. Based on data related to intercalated and unintercalated meltblown materials under given process conditions, a product performance prediction model of intercalated meltblown materials was established under different process parameters (receiving distance, hot air velocity). The structural variables (thickness, porosity, and compressive resilience), the change in product performance, and the relationship between structural variables and product performance (filtration resistance, efficiency, air permeability) after intercalation were studied. Multiple regression analysis was used to analyze the structural variables, and evaluation of the regression results were made using R2, MSE, SSR, and SST. A BP neural network prediction model for product performance was established. The BP neural network model was used to find the maximum filtration efficiency. The study provides theoretical support for regulating product performance by solving the maximum filtration efficiency using BP neural network model.

17.
Plants (Basel) ; 12(2)2023 Jan 10.
Article in English | MEDLINE | ID: mdl-36679038

ABSTRACT

Brassica napus L. is a vital plant oil resource worldwide. The fatty acid biosynthesis and oil accumulation in its seeds are controlled by several genetic and environmental factors, including daytime and nighttime temperatures. We analyzed changes in oleic and erucic acid content in two double haploid (DH) lines, DH0729, a weakly temperature-sensitive line, and DH0815, a strongly temperature-sensitive line, derived from B. napus plants grown at different altitudes (1600, 1800, 2000, 2200, and 2400 m a.s.l., 28.85° N, 112.35° E) and nighttime temperatures (20/18, 20/16, 20/13 and 20/10 °C, daytime/nighttime temperature). Based on medium- and long-chain fatty acid metabolites, the total oleic acid content 35 and 43 days after flowering was significantly lower in low nighttime temperature (LNT, 20/13 °C) plants than in high nighttime temperature (HNT, 20/18 °C) plants (HNT: 58-62%; LNT: 49-54%; an average decrease of 9%), and the total erucic acid content was significantly lower in HNT than in LNT plants (HNT: 1-2%; LNT: 8-13%; an average increase of 10%). An RNA-seq analysis showed that the expression levels of SAD (LOC106366808), ECR (LOC106396280), KCS (LOC106419344), KAR (LOC106367337), HB1(LOC106430193), and DOF5 (LOC111211868) in STSL seeds increased under LNT conditions. In STSL seeds, a base mutation in the cis-acting element involved in low-temperature responsiveness (LTR), the HB1 and KCS promoter caused loss of sensitivity to low temperatures, whereas that of the KCS promoter caused increased sensitivity to low temperatures.

18.
Drug Metab Dispos ; 51(3): 350-359, 2023 03.
Article in English | MEDLINE | ID: mdl-36627162

ABSTRACT

Recent advancements in single-cell technologies have enabled detection of RNA, proteins, metabolites, and xenobiotics in individual cells, and the application of these technologies has the potential to transform pharmacological research. Single-cell data has already resulted in the development of human and model species cell atlases, identifying different cell types within a tissue, further facilitating the characterization of tumor heterogeneity, and providing insight into treatment resistance. Research discussed in this review demonstrates that distinct cell populations express drug metabolizing enzymes to different extents, indicating there may be variability in drug metabolism not only between organs, but within tissue types. Additionally, we put forth the concept that single-cell analyses can be used to expose underlying variability in cellular response to drugs, providing a unique examination of drug efficacy, toxicity, and metabolism. We will outline several of these techniques: single-cell RNA-sequencing and mass cytometry to characterize and distinguish different cell types, single-cell proteomics to quantify drug metabolizing enzymes and characterize cellular responses to drug, capillary electrophoresis-ultrasensitive laser-induced fluorescence detection and single-probe single-cell mass spectrometry for detection of drugs, and others. Emerging single-cell technologies such as these can comprehensively characterize heterogeneity in both cell-type-specific drug metabolism and response to treatment, enhancing progress toward personalized and precision medicine. SIGNIFICANCE STATEMENT: Recent technological advances have enabled the analysis of gene expression and protein levels in single cells. These types of analyses are important to investigating mechanisms that cannot be elucidated on a bulk level, primarily due to the variability of cell populations within biological systems. Here, we summarize cell-type-specific drug metabolism and how pharmacologists can utilize single-cell approaches to obtain a comprehensive understanding of drug metabolism and cellular heterogeneity in response to drugs.


Subject(s)
Neoplasms , Proteomics , Humans , Proteomics/methods , Precision Medicine/methods , Proteins , Single-Cell Analysis/methods
19.
Mar Drugs ; 22(1)2023 Dec 27.
Article in English | MEDLINE | ID: mdl-38248643

ABSTRACT

Three redox-sensitive nanocarriers were rationally designed based on amphiphilic low molecular weight chitosan-cystamine-octylamine/dodecylamin/cetylamine (LC-Cys-OA, LC-Cys-DA, LC-Cys-CA) conjugates containing disulfide linkage for maximizing therapeutic effect by regulating hydrophobic interaction. The resultant spherical micelles had the characteristics of low CMC, suitable size, excellent biosafety and desired stability. The drug-loaded micelles were fabricated by embedding doxorubicin (Dox) into the hydrophobic cores. The effect of hydrophobic chain lengths of amphiphilic conjugates on encapsulation capacity, redox sensitivity, trigger-release behavior, cellular uptake efficacy, antitumor effect and antimigratory activity of Dox-loaded micelles was systematically investigated. Studies found that Dox-loaded LC-Cys-CA micelle had superior loading capacity and enhanced redox sensitivity compared with the other two micelles. Release assay indicated that the three Dox-loaded micelles maintained sufficiently stability in normal blood circulation but rapidly disintegrated in tumor cells. More importantly, the LC-Cys-CA micelle with a longer hydrophobic chain length exhibited a higher accumulative Dox release percentage than the other two micelles. Additionally, an increase in hydrophobic chain lengths of amphiphilic conjugates improved cellular uptake efficiency, antitumor effect and antimigration activity of Dox-loaded micelles, which could be explained by enhanced loading ability and redox sensitivity. Our research was expected to provide a viable platform for achieving a desired therapeutic efficacy via the alteration of hydrophobic interaction.


Subject(s)
Chitosan , Micelles , Drug Liberation , Drug Delivery Systems , Doxorubicin/pharmacology , Oxidation-Reduction
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