ABSTRACT
Bladder cancer (BC) represents a prevalent and formidable malignancy necessitating innovative diagnostic and therapeutic strategies. Circular RNAs (circRNAs) have emerged as crucial regulators in cancer biology. In this study, we comprehensively evaluated ferroptosis levels in BC cells utilizing techniques encompassing lipid peroxidation assessment, transmission electron microscopy, and malondialdehyde (MDA) measurement. Additionally, we probed into the mechanistic intricacies by which circRNAs govern BC, employing RNA pull-down, RNA immunoprecipitation (RIP), and immunoprecipitation (IP) assays. Our investigation unveiled circSIRT5, which displayed significant downregulation in BC. Notably, circSIRT5 emerged as a promising prognostic marker, with diminished expression correlating with unfavorable clinical outcomes. Functionally, circSIRT5 was identified as an inhibitor of BC progression both in vitro and in vivo. Mechanistically, circSIRT5 exerted its tumor-suppressive activities through the formation of a ternary complex involving circSIRT5, SYVN1, and PHGDH. This complex enhanced the ubiquitination and subsequent degradation of PHGDH, ultimately promoting ferroptosis in BC cells. This ferroptotic process contributed significantly to the inhibition of tumor growth and metastasis in BC. In addition, FUS was found to accelerate the biogenesis of circSIRT5 in BC. These findings provide valuable insights into the pivotal role of circSIRT5 in BC pathogenesis, underscoring its potential as a diagnostic biomarker and therapeutic target for this malignancy.
ABSTRACT
Metabolic responses to cellular stress are pivotal in cell ferroptosis, with mitophagy serving as a crucial mechanism in both metabolic processes and ferroptosis. This study aims to elucidate the effects of high glucose on cardiomyocytes (CMs) and cardiac fibroblasts (CFs) regarding ferroptosis and to uncover the underlying mechanisms involved. We examined alterations in glycolysis, mitochondrial oxidative phosphorylation (OXPHOS), and mitophagy, which are essential for metabolic adaptations and ferroptosis. High glucose exposure induced ferroptosis specifically in CMs, while CFs exhibited resistance to ferroptosis, increased glycolytic activity, and no change in OXPHOS. Moreover, high glucose treatment enhanced mitophagy and upregulated mitochondrial ferritin (FTMT). Notably, the combination of FTMT and the autophagy-related protein nuclear receptor coactivator 4 (NCOA4) increased under high glucose conditions. Silencing FTMT significantly impeded mitophagy and eliminated ferroptosis resistance in CFs cultured under high glucose conditions. The transcription factor forkhead box A1 (FOXA1) was upregulated in CFs upon high glucose exposure, playing a crucial role in the increased expression of FTMT. Within the 5'-flanking sequence of the FTMT mRNA, approximately -500 nt from the transcription initiation site, three putative FOXA1 binding sites were identified. High glucose augmented the binding affinity between FOXA1 and these sequences, thereby promoting FTMT transcription. In summary, high glucose upregulated FOXA1 expression and stimulated FTMT promoter activity in CFs, thereby promoting FTMT-dependent mitophagy and conferring ferroptosis resistance in CFs.
ABSTRACT
Evidence on the link of long-term exposure to ozone (O3) with childhood asthma, rhinitis, conjunctivitis and eczema is inconclusive. We did a population-based cross-sectional survey, including 177,888 children from 173 primary and middle schools in 14 Chinese cities. A satellite-based spatiotemporal model was employed to assess four-year average O3 exposure at both residential and school locations. Information on asthma, allergic rhinitis, eczema and conjunctivitis was collected by a standard questionnaire developed by the American Thoracic Society. We used generalized non-linear and linear mixed models to test the associations. We observed linear exposure-response associations between O3 and all outcomes. The odds ratios of doctor-diagnosed asthma, rhinitis, eczema, and conjunctivitis associated with per interquartile increment in home-school O3 concentration were 1.31 (95 % confidence interval [CI]: 1.28, 1.34), 1.25 (95 %CI: 1.23, 1.28), 1.19 (95 %CI: 1.16, 1.21), and 1.28 (95 %CI: 1.21, 1.34), respectively. Similar associations were observed for asthma-related outcomes including current asthma, wheeze, current wheeze, persistent phlegm, and persistent cough. Moreover, stronger associations were observed among children who were aged > 12 years, physically inactive, and exposed to higher temperature. In conclusion, long-term O3 exposure was associated with higher risks of asthma, allergic rhinitis, conjunctivitis and eczema in children.
Subject(s)
Air Pollutants , Asthma , Cities , Conjunctivitis , Eczema , Ozone , Rhinitis , Humans , Ozone/analysis , Ozone/toxicity , Child , China/epidemiology , Asthma/epidemiology , Asthma/chemically induced , Eczema/epidemiology , Eczema/chemically induced , Male , Female , Rhinitis/epidemiology , Rhinitis/chemically induced , Air Pollutants/toxicity , Air Pollutants/analysis , Conjunctivitis/chemically induced , Conjunctivitis/epidemiology , Cross-Sectional Studies , Environmental Exposure/adverse effects , AdolescentABSTRACT
Most known chemiluminescence (CL) systems are flash-type that generate weak luminescence and decline quickly after dozens of seconds, while the glow-type CL systems have stable emission for an extended period to achieve accurate quantitation. In this work, a long-term CL system based on hydrazine-hydrate (N2H4·H2O) modified carbon quantum dots (N-CQDs) as a luminescent probe, with K2S2O8 and H2O2 as co-reactants, was proposed. The CL emission enhanced by H2O2 increased 18-fold more than that of N-CQDs and K2S2O8 direct reaction, and decayed by 5% of the maximum intensity over 700 s. In the reaction system, K2S2O8 and H2O2 co-reactants can promote each other to continuously generate corresponding radicals (â¢OH, O2â¢-, 1O2), which in turn trigger the CL emission of N-CQDs. This phenomenon was identified as the primary cause for the production of persistent CL. In addition, a stable and selective CL sensor based on the N-CQDs-K2S2O8-H2O2 CL enhancing system was developed for ascorbic acid quantitation in the linear range from 0.1 to 10.0 mM with a detection limit of 0.036 mM. The method has been applied to the analysis of tablet samples and holds potential in pharmaceutical analysis field.
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Energy consumption from air cooling systems in summer, water scarcity in hot regions, and the functional reusability of waste paper are emerging environmental problems. Finding solutions to these problems simultaneously remains a significant challenge. Herein, a superhydrophobic passive cooling Cellulose-CaCO3 film with hierarchical nano-sheets was fabricated to realize daytime radiative cooling with a temperature drop of 15-20 °C in summer and water harvesting with harvesting efficiency of 387 mg cm-2h-1 bd utilization of recycled waste paper. The superhydrophobic Cellulose-CaCO3 film demonstrates its self-cleaning properties against inorganic and organic pollutants. Furthermore, the superhydrophobicity of the film was maintained after base/acid corrosions, dynamic water flushing, and thermal treatment at 100 °C for 7 h, exhibiting good durability of the superhydrophobicity. Moreover, the superhydrophobic Cellulose-CaCO3 film is nonflammable after exposure to fire combustion for 1 min. In addition to waste paper, waste maize straws, and pasteboards were also collected to produce superhydrophobic passive cooling films. Results indicate that the above three cellulose-based raw materials can be well used to prepare durable superhydrophobic passive cooling materials. Environmental toxicology assessments confirm the safety of the material. This study not only provides a protocol for preparing superhydrophobic materials; but also demonstrates their potential for passive cooling and water harvesting.
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The development of two-dimensional (2D) materials has received wide attention as a generation of optoelectronics, thermoelectric, and other applications. In this study, a novel 2D material, PbN, is proposed as an elemental method using the prototype of a recent reported nitride (J. Phys. Chem. C 2023, 127, 43, 21,006-21014). Based on first-principle calculations, the PbN monolayer is investigated as stable at 900 K, and the isotropic mechanical behavior is addressed by the Young's modulus and Poisson's ratio at 67.4 N m-1 and 0.15, respectively. The PbN monolayer also presents excellent catalytic performance with Gibbs free energy of 0.41 eV. Zero bandgap is found for the PbN monolayer, and it can be opened at about 0.128 eV by forming a heterostructure with CdO. Furthermore, the PbN/CdO is constructed by Van der Waals interaction, while the apparent potential drop and charge transfer are investigated at the interface. The PbN/CdO heterostructure also possesses excellent light absorption properties. The results provide theoretical guidance for the design of layered functional materials.
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The powerful capability of reconfigurable intelligent surfaces (RISs) in tailoring electromagnetic waves and fields has put them under the spotlight in wireless communications. However, the current designs are criticized due to their poor frequency selectivity, which hinders their applications in real-world scenarios where the spectrum is becoming increasingly congested. Here we propose a filtering RIS to feature sharp frequency-selecting and 2-bit phase-shifting properties. It permits the signals in a narrow bandwidth to transmit but rejects the out-of-band ones; meanwhile, the phase of the transmitted signals can be digitally controlled, enabling flexible manipulations of signal propagations. A prototype is designed, fabricated, and measured, and its high quality factor and phase-shifting characteristics are validated by scattering parameters and beam-steering phenomena. Further, we conduct a wireless communication experiment to illustrate the intriguing functions of the RIS. The filtering behavior enables the RIS to perform wireless signal manipulations with anti-interference ability, thus showing big potential to advance the development of next-generation wireless communications.
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To realize strong donor-acceptor face-to-face stacking for efficient through-space charge transfer-type thermally activated delayed fluorescence, a conceptually new design strategy is proposed to couple flexible bridges with adequate rigidity via built-in intramolecular hydrogen bonds (IHBs). The resulting emitter ACE-CN has a planarized benzyl methyl ether bridge self-anchored by the C-H···O IHB and shows a high photoluminescence quantum efficiency of 93%. The solution- and vacuum-processed devices exhibited high external quantum efficiencies of 11.8% and 24.7%, respectively.
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Environmental pollution and poor feed quality pose potential threats to aquatic organisms and human health, representing challenges for the aquaculture industry. In light of the rising demand for aquatic organisms, there is an urgent need to improve aquacultural production and protect the products from contamination. Char, a carbonaceous material derived through pyrolysis of organic carbon-rich biomass, has proven advantages in soil, air, and water remediation. While char's performance and the associated physicochemical characteristics depend strongly on the pyrolysis temperature, residence time, and feedstock type, char generally shows advantages in pollutant removal from the environment and livestock. This enables it to enhance the health and growth performance of livestock. Given the growing attention to char application in aquaculture in recent years, this review summarises major studies on three applications: aquacultural water treatment, sediment remediation, and char-feed supplement. Most of these studies have demonstrated char's positive effects on pollutant removal from organisms and aquacultural environments. Moreover, adopting char as fish feed can improve fish growth performance and the condition of their intestinal villi. However, due to insufficient literature, further investigation is needed into the mechanistic aspects of pollutants removal in aquatic organisms by char as a feed additive, such as the transportation of char inside aquatic organisms, the positive and negative effects of char on these products, and how char alters the gut microbiota community of these products. This paper presents an overview of the current application of char in aquaculture and highlights the research areas that require further investigation to enrich future studies.
Subject(s)
Aquaculture , Charcoal , Aquaculture/methods , Charcoal/chemistry , Animal Feed/analysis , Animals , Water Pollutants, Chemical/analysis , Water Purification/methods , Environmental Restoration and Remediation/methods , FishesSubject(s)
Bronchoscopy , Fever , Humans , Bronchoscopy/methods , Fever/etiology , Male , Female , Middle AgedABSTRACT
BACKGROUND: Carotid duplex ultrasonography (DUS) is the primary screening tool for carotid artery stenosis, but has low reliability. MHR, which is the ratio of monocytes to high-density lipoprotein cholesterol (HDL-C), can be a marker for the degree and distribution of extracranial and intracranial atherosclerotic stenosis. OBJECTIVE: We determined the diagnostic value of DUS+MHR for internal carotid artery (ICA) stenosis. METHODS: We divided 273 hospitalized patients into non-stenosis (<50%) and ICA stenosis (≥50%) groups based on Digital Subtraction Angiography (DSA). We determined the peak systolic velocity (PSV) in the ICA on DUS, calculated the MHR, and investigated their relationship with ICA stenosis. RESULTS: On DSA, 34.1% (93/273) patients had moderate-to-severe ICA stenosis. DUS and DSA showed low concordance for detecting ICA stenosis (kappa = 0.390). With increasing age, the incidence of moderate-to-severe ICA stenosis increased. PSV, monocyte count, and MHR were significantly greater in the stenosis group than in the non-stenosis group (P < 0.001), while the HDL-C level was significantly lower (P = 0.001). PSV (OR: 1.020, 95% CI: 1.011-1.029, P < 0.001) and MHR (OR: 5.662, 95% CI: 1.945-16.482, P = 0.002) were independent risk factors for ICA stenosis. The area under the receiver operating characteristic curve of PSV+MHR (0.819) was significantly higher than that of PSV or MHR alone (77.42% sensitivity, P = 0.0207; 73.89% specificity, P = 0.0032). CONCLUSION: The combination of ICA PSV on DUS and MHR is better than PSV alone at identifying ICA stenosis and is well-suited to screen high-risk patients.
Subject(s)
Angiography, Digital Subtraction , Carotid Stenosis , Monocytes , Humans , Carotid Stenosis/diagnostic imaging , Carotid Stenosis/blood , Male , Female , Aged , Middle Aged , Angiography, Digital Subtraction/methods , Carotid Artery, Internal/diagnostic imaging , Ultrasonography, Doppler, Duplex/methods , Cholesterol, HDL/blood , Aged, 80 and over , ROC Curve , Ultrasonography, Carotid ArteriesABSTRACT
Patients with schizophrenia often encounter notable weight gain during their illness, heightening the risk of metabolic diseases. While previous studies have noted a correlation between obesity and cognitive impairment in schizophrenia, many were cross-sectional, posing challenges in establishing a causal relationship between weight gain and cognitive function. The aim of this longitudinal study is to examine the relationship between weight gain and cognitive function in patients with first-episode schizophrenia (FES) during the initial 6-month antipsychotic treatments. Employing linear and logistic regression analyses, the study involved 337 participants. Significantly, baseline scores in processing speed (OR = 0.834, p = 0.007), working memory and attention (OR = 0.889, p = 0.043), and executive function (OR = 0.862, p = 0.006) were associated with clinically relevant weight gain (CRW, defined as an increase in body weight > 7%) at the 6-month endpoint. On the other hand, CRW correlated with improvements in the Brief Visuospatial Memory Test (p = 0.037). These findings suggest that patients with lower baseline cognitive performance undergo more substantial weight gain. Conversely, weight gain was correlated with cognitive improvements, particularly in the domain of visual learning and memory. This suggested a potential bidirectional relationship between weight gain and cognitive function in first-episode schizophrenia patients.
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Improving the humification of compost through a synergistic approach of biotic and abiotic methods is of great significance. This study employed a composite reagent, comprising Fenton-like agents and effective microorganisms (EM) to improve humification. This composite reagent increased humic-acid production by 37.44 %, reaching 39.82 g kg-1, surpassing the control group. The composite reagent synergistically promoted micromolecular fulvic acid and large humic acid production. Collaborative mechanism suggests that Fenton-like agents contributed to bulk residue decomposition and stimulated the evolution of microbial communities, whereas EMs promoted highly aromatic substance synthesis and adjusted the microbial community structure. Sequencing analysis indicates the Fenton-like agent initiated compost decomposition by Firmicutes, and EM reduced the abundance of Virgibacillus, Lentibacillus, and Alcanivorax. Applied as an organic fertilizer in Brassica chinensis L. plantations, the composite reagent considerably improved growth and photosynthetic pigment content. This composite reagent with biotic and abiotic components provides a learnable method for promoting humification.
Subject(s)
Benzopyrans , Composting , Humic Substances , Hydrogen Peroxide , Iron , Composting/methods , Iron/chemistry , Iron/pharmacology , Hydrogen Peroxide/pharmacology , Brassica , Soil Microbiology , Soil/chemistry , Bacteria , FertilizersABSTRACT
To assess the total daily mercury intake and main exposure sources of residents, six food groups, including marine fish, freshwater fish, poultry, livestock, vegetables, and cereals, were collected from five districts of Chengdu, China. The median concentrations of total mercury (THg) and methylmercury (MeHg) were 12.8 and 6.94 µg kg-1 ww, respectively. Cereals (32.2%), vegetables (30.5%), and livestock (16.2%) contributed to a much larger extent to the total consumption for the participants in Chengdu. All food categories that contributed the most of THg (2.16 µg day-1) and MeHg 1.44 (µg day-1) to the daily intake in Chengdu were cereals and marine fish, respectively. The total Hazard Ratios values below 1 in this study indicate that there is no health risk associated with Hg ingestion from the consumption of these foods for the residents in Chengdu.
Subject(s)
Mercury , Methylmercury Compounds , Animals , Humans , Mercury/analysis , Environmental Monitoring , Food Contamination/analysis , Methylmercury Compounds/analysis , Diet , Risk Assessment , Vegetables , Fishes , Edible Grain/chemistry , ChinaABSTRACT
Background: The early safety and efficacy of Castor branch stents have been demonstrated. However, the effect of aortic arch morphology on endovascular therapy remains an unresolved issue. This study aims to assess the impact of aortic arch morphology on the early outcomes of endovascular repair using Castor stent graft in patients who have acute type B aortic dissection involving the left subclavian artery (LSA). Methods: This is a retrospective cohort study. From January 2019 to December 2021, forty-one patients scheduled for thoracic endovascular aortic repair (TEVAR) of TBADs from Beijing Anzhen Hospital were enrolled in this retrospective cohort study and divided into two groups based on the length of the proximal landing zone left common carotid artery-LSA (PLZ LCCA-LSA), specifically the distance between the LCCA and the LSA (group A ≤10 mm and group B >10 mm). The study recorded technical success, mortality and aortic-related post-operative adverse events. Morphological indices were analyzed including the bird-beak configuration. The bird-beak configuration refers to the wedge-shaped gap between the undersurface of the endograft and the lesser curvature of the arch. The relationship between the risk of bird-beak configuration and PLZ was assessed with logistic regression analysis. Meanwhile, the relationship between the risk of aortic-related adverse events and bird-beak configuration was assessed with logistic regression analysis. Follow-up data were analyzed by Kaplan-Meier life table analysis. Results: The study included 41 patients with a mean age of 63.1±9.2 years, of which 80.5% were male. 18 patients from group A and 23 patients from group B were included in the comparative analysis. There were no significant differences in aortic-related adverse events, bird-beak phenomenon and re-intervention between groups A and B in 30-day outcomes. Six-month outcomes: aortic-related adverse events and the bird-beak phenomenon were observed in 11 (26.8%) and 12 (29.3%) patients, respectively. There was a significant difference in the occurrence of aortic-related adverse events (P=0.036) and bird-beak phenomenon (P=0.002) between groups A and B. In comparison to group B, the aortic-related adverse event rate was significantly higher in group A, with event-free rates of 83.3%, 83.3%, and 72.2% at 1, 3, and 6 months, respectively (P=0.020). Multivariable logistic regression analyses revealed that PLZ LCCA-LSA length [odds ratio (OR) 0.79; 95% CI: 0.64 to 0.97; P=0.026] was significantly associated with the occurrence of the bird-beak configuration, and bird-beak (OR 17.19; 95% CI: 2.24 to 131.81; P=0.006) was a significant risk factor for aortic-related adverse events. Conclusions: TEVAR with LSA revascularization has good early outcomes. However, it is more susceptible to aortic adverse events when the PLZ LCCA-LSA is less than 10 mm in length. This should be carefully considered, taking into account the risks and benefits.
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Aging can lead to various disorders in organisms and with the escalating impact of population aging, the incidence of age-related diseases is steadily increasing. As a major risk factor for chronic illnesses in humans, the prevention and postponement of aging have become focal points of research among numerous scientists. Aging biomarkers, which mirror molecular alterations at diverse levels in organs, tissues, and cells, can be used to monitor and evaluate biological changes associated with aging. Currently, aging biomarkers are primarily categorized into physiological traits, imaging characteristics, histological features, cellular-level alterations, and molecular-level changes that encompass the secretion of aging-related factors. However, in the context of the musculoskeletal soft tissue system, aging-related biological indicators primarily involve microscopic parameters at the cellular and molecular levels, resulting in inconvenience and uncertainty in the assessment of musculoskeletal soft tissue aging. To identify convenient and effective indicators, we conducted a comprehensive literature review to investigate the correlation between ectopic mineralization and age-related changes in the musculoskeletal soft tissue system. Here, we introduce the concept of ectopic mineralization as a macroscopic, reliable, and convenient biomarker for musculoskeletal soft tissue aging and present novel targets and strategies for the future management of age-related musculoskeletal soft tissue disorders.
Subject(s)
Calcinosis , Ossification, Heterotopic , Humans , Aged , Osteogenesis , Ossification, Heterotopic/etiology , Ossification, Heterotopic/pathology , Aging , BiomarkersABSTRACT
BACKGROUND: Genetic polymorphism of KIAA1217 has been reported to be associated with lumbar disc herniation (LDH) in different populations such as Japanese population and Finnish population. This study aimed to explore whether the genetic polymorphism of KIAA1217 is functionally associated with LDH in Chinese population. METHODS: SNP rs16924573 of KIAA1217 was genotyped in 1272 patients and 1248 healthy controls. The mRNA expression of KIAA1217 in the intervertebral disc was analyzed for 84 patients and 32 controls. The differences of genotype and allele distributions between LDH patients and healthy controls were evaluated using the Chi-square test. One-way ANOVA test was used to compare the relationship between genotypes and tissue expression of KIAA1217. RESULTS: Patients were found to have significantly higher frequency of genotype GG of rs16924573 than the controls (64.2% vs. 52.8%, p<0.001). The frequency of allele G was remarkably higher in the patients than in the controls (79.8% vs. 73.2%, p<0.001), with an OR of 1.45 (95% confidential interval=1.27-1.66). Compared with the controls, LDH patients were observed to have significantly decreased expression of KIAA1217. Patients with genotype GG had remarkably lower mRNA expression of KIAA1217 than those with genotype AG or AA (p=0.01). CONCLUSIONS: SNP rs16924573 of KIAA1217 could be functionally associated with LDH in the Chinese population. More in vivo and vitro experiments need to be carried out to further clarify the regulatory mechanism of functional variants in KIAA1217.
Subject(s)
Intervertebral Disc Degeneration , Intervertebral Disc Displacement , Humans , Case-Control Studies , China/epidemiology , Genetic Predisposition to Disease/genetics , Intervertebral Disc Degeneration/genetics , Intervertebral Disc Displacement/genetics , Lumbar Vertebrae , Polymorphism, Single Nucleotide/genetics , RNA, MessengerABSTRACT
Smart electromagnetic interference (EMI) shielding materials are of great significance in coping with the dynamic performance demands of cutting-edge electronic devices. However, smart EMI shielding materials are still in their infancy and face a variety of challenges (e.g., large thickness, limited tunable range, poor reversibility, and unclear mechanisms). Here, we report a method for controllable shielding electromagnetic (EM) waves through subwavelength structure changes regulated by the customized structure via a direct printing route. The highly conductive MXene ink is regulated with metal ions (Al3+ ions), giving superb metallic conductivity (â¼5000 S cm-1) for the printed lines without an annealing treatment. The reversible tunability of EMI shielding effectiveness (SE) ranging from 8.2 dB ("off" state) to 34 dB ("on" state) is realized through the controllable modulation of subwavelength structure driven by stress. This work provides a feasible strategy to develop intelligent shielding materials and EM devices.
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Soil samples were collected in at different depths from the conflagration area in Liangshan Yi Autonomous Region, China, to investigate the distribution characteristics and ecological and human health risks of heavy metals after a wildfire. The samples collected comprise wildfire ash (WA) above the soil surface, ash soil (AS) 0-5 cm, and plain soil (PS) 5-15 cm below the soil surface. Additionally, reference soil (RS) was collected from a nearby unburned area at the same latitude as the conflagration area. The results showed that the concentrations of zinc (Zn), copper (Cu), lead (Pb), and cadmium (Cd) in the WA and AS were significantly higher than in reference soil (RS) (p < 0.05). Concentrations of Pb in the PS were 2.52 times higher than that in RS (17.9 mg kg-1) (p < 0.05). The AS and WA had the highest Index of potential ecological risks (RI > 600). In addition, The Cd in AS and WA contributed the most to the highest Improved nemerow index (INI) and RI with a contribution of more than 80%. The concentration of heavy metals was used to establish non-carcinogenic effects and cancer risks in humans via three exposure pathways: accident ingestion of soil, dermal contact with soil, and inhalation of soil particles. Hazard index (HI) values of each sample were all less than 1, indicating the non-carcinogenic risk was within the acceptable range and would not adversely affect the local population's health. The Cancer risk (CR) values of Cr, As, Cd, and Ni were all below 1 × 10-6, indicating that heavy metal pollution from this wildfire did not pose a cancer risk to residents.
Subject(s)
Metals, Heavy , Neoplasms , Soil Pollutants , Wildfires , Humans , Soil , Environmental Monitoring , Cadmium , Lead , Risk Assessment , Soil Pollutants/analysis , Metals, Heavy/analysis , ChinaABSTRACT
Executive function, including working memory, attention and inhibitory control, is crucial for decision making, thinking and planning. Lisdexamfetamine, the prodrug of d-amphetamine, has been approved for treating attention-deficit hyperactivity disorder and binge eating disorder, but whether it improves executive function under non-disease condition, as well as the underlying pharmacokinetic and neurochemical properties, remains unclear. Here, using trial unique non-matching to location task and five-choice serial reaction time task of rats, we found lisdexamfetamine (p.o) enhanced spatial working memory and sustained attention under various cognitive load conditions, while d-amphetamine (i.p) only improved these cognitive performances under certain high cognitive load condition. Additionally, lisdexamfetamine evoked less impulsivity than d-amphetamine, indicating lower adverse effect on inhibitory control. In vivo pharmacokinetics showed lisdexamfetamine produced a relative stable and lasting release of amphetamine base both in plasma and in brain tissue, whereas d-amphetamine injection elicited rapid increase and dramatical decrease in amphetamine base levels. Microdialysis revealed lisdexamfetamine caused lasting release of dopamine within the medial prefrontal cortex (mPFC), whereas d-amphetamine produced rapid increase followed by decline to dopamine level. Moreover, lisdexamfetamine elicited more obvious efflux of noradrenaline than that of d-amphetamine. The distinct neurochemical profiles may be partly attributed to the different action of two drugs to membranous catecholamine transporters level within mPFC, detecting by Western Blotting. Taken together, due to its certain pharmacokinetic and catecholamine releasing profiles, lisdexamfetamine produced better pharmacological action to improving executive function. Our finding provided valuable evidence on the ideal pharmacokinetic and neurochemical characteristics of amphetamine-type psychostimulants in cognition enhancement.