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BACKGROUND AND OBJECTIVE: Recent studies have highlighted the key role of the ATP-binding cassette (ABC) transporters, including the P-glycoprotein (P-gp), the breast cancer resistance protein (BCRP), and the multi-drug resistance protein 4 (MRP4) in limiting the brain distribution of several antiviral agents. In this study, we investigated whether the inhibition of these transporters increases the permeability of the blood-brain barrier (BBB) to ganciclovir. METHODS: A microdialysis and high-performance liquid chromatographic method was developed to monitor the concentrations of unbound ganciclovir in the brain interstitial fluid and plasma, with and without the administration of ABC transporter inhibitors. Pharmacokinetic parameters, including the area under the plasma concentration-time curve from time 0 to time of the last measurable analyte concentration (AUC0-t,plasma), the area under the brain interstitial fluid concentration-time curve from time 0 to time of the last measurable analyte concentration (AUC0-t,brain), and the unbound brain-to-plasma concentration ratio (Kp,uu,brain) were calculated. RESULTS: The mean AUC0-t,plasma, AUC0-t,brain, and Kp,uu,brain in rats who received ganciclovir (30 mg/kg, intraperitoneal) alone were 1090 min·µg/mL, 150 min·µg/mL, and 14%, respectively. After the administration of tariquidar (inhibitor of P-gp), Ko143 (inhibitor of BCRP), or MK-571 (inhibitor of MRP4), the Kp,uu,brain of ganciclovir increased to 31 ± 2.1%, 26 ± 1.3%, and 32 ± 2.0%, respectively. CONCLUSIONS: The findings of this study suggest that ABC transporters P-gp, BCRP, and MRP4 mediate the efflux of ganciclovir at the BBB and that the inhibition of these transporters facilitates the penetration of the BBB by ganciclovir.
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PURPOSE: This study compared the efficacy and safety of intravenous chemotherapy combined with intravesical chemotherapy versus intravesical chemotherapy alone for high-risk nonmuscle invasive bladder cancer (HRNMIBC) patients after transurethral resection of the bladder tumor (TURBT) surgery. METHODS: A retrospective analysis was performed on 349 HRNMIBC cases admitted to TangDu hospital between January 2014 and June 2019. After TURBT, 262 patients received intravesical chemotherapy alone, whereas 87 patients underwent intravesical chemotherapy in combination with intravenous chemotherapy. The recurrence rate and progression rate were assessed by Chi-square test, the prognostic factors for tumor recurrence were predicted by univariable and multivariable Cox hazards analyses, recurrence-free survival (RFS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. RESULTS: In this study, the recurrence rate was 24.7% (19/77) in the intravenous chemotherapy combined group and 41.6% (102/245) in the intravesical chemotherapy group, while the progression rate was 6.5% (5/77) and 14.3% (35/245) in the two groups respectively. The two groups differed significantly in recurrence rate (p = 0.007) while the progression rate did not show a significant difference (p = 0.071). Multivariable analyses revealed that additional intravenous chemotherapy treatment was an independent prognostic factor for tumor recurrence in the cohort (hazard ratio [HR], 0.495, 95% confidence interval [CI], 0.275-0.892, p = 0.019). Kaplan-Meier curves showed significant differences in RFS and PFS between the two groups, with a log-rank P value of p < 0.005 and p = 0.045, respectively. Grade 3/4 toxicity was reported in 2 of 77 patients in the intravenous chemotherapy combined group, including nausea/vomiting 1.3% (1/77) and hypoleukemia 1.3% (1/77). CONCLUSION: Intravenous chemotherapy of gemcitabine and cisplatin combined with intravesical chemotherapy after TURBT can effectively reduce the postoperative recurrence rate, most toxicities were minor and reversible, and it may be considered as a new choice for HRNMIBC patients.
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AIMS: The aim of this study was to assess the influence of the major transporters at blood-brain barrier and blood-cerebrospinal fluid barrier on levofloxacin (LVFX) pharmacokinetics in rat. To explore the different effects of transporters on drug concentrations in cerebrospinal fluid (CSF) and brain extracellular fluid (ECF). METHODS: High-performance liquid chromatography coupled with microdialysis was used to continuously and synchronously measure unbound concentrations of LVFX in rat blood, hippocampal ECF, and lateral ventricle CSF for comprehensive characterization of brain pharmacokinetics. The role of transporters in the brain efflux mechanism of LVFX was analyzed in the absence and presence of various transporter inhibitors. RESULTS: Following LVFX (50 mg/kg) administration, the unbound partition coefficient of LVFX in brain ECF and CSF (Kp,uu,ECF and Kp,uu,CSF ) were 34.0 ± 1.7% and 41.2 ± 2.4%, respectively. When probenecid was coadministered with LVFX, the AUC and the mean residence time (MRT) in rat blood increased significantly (p < 0.05). After MK571 intervention, 1.35-fold and 1.16-fold increases in Kp,uu,ECF and Kp,uu,CSF were observed, respectively (p < 0.05). Treatment with Ko143 increased the levels of LVFX in brain ECF. The difference in LVFX concentration in brain ECF and CSF was <3-fold with or without treatment with transporter inhibitors. CONCLUSION: Efflux of LVFX from the central nervous system (CNS) involves multidrug resistance-associated proteins (MRPs), breast cancer resistance protein (BCRP), and organic anion transporters (OATs). MRPs play an important role in mediating the brain/CSF-to-blood efflux of LVFX. LVFX concentrations in CSF can be used as a surrogate to predict the concentrations inside brain parenchyma.
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Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Encéfalo , Levofloxacino , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Animais , Ratos , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Levofloxacino/farmacocinética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismoRESUMO
Topologically nontrivial electronic states are recently found in a family of noncentrosymmetric transition metal pnictidesTRuX(T=Zr, Hf;X=P, As), presenting a unique platform for superconductivity to interplay with topological electronic states and asymmetric spin-orbit coupling. Here, we investigate the superconducting order parameter of HfRuP and ZrRuAs by measuring the magnetic penetration depth changeΔλ(T)using a method based on the tunnel-diode oscillator. Both compounds show clear exponential temperature dependence inΔλ(T)at low temperatures, suggesting fully-gapped superconductivity. Moreover, the superfluid densities in both HfRuP and ZrRuAs can be reasonably described by ans-wave superconducting model.
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Acute hypobaric hypoxia (AHH) exposure causes altitude mountain sickness (AMS) and life-threatening high altitude cerebral edema (HACE). Despite decades of research, the role of cerebral blood flow (CBF) changes in the pathophysiology of severe AMS remains unclear. The current study evaluated spatiotemporal responses of CBF associated with HACE in mice during the early stages of ascent to high altitudes. First, mice were exposed to AHH to test their tolerance to increasing altitudes (3000-8000 m). Because of its significant influence on both locomotor activity and rotarod behavior tests in mice, further observations were initiated at an altitude of 6000 m to investigate the specific pathophysiology of AMS. Compared with controls, laser speckle contrast imaging (LSCI) revealed a significant decrease in CBF during the early stage (0.5-24 h) at an altitude of 6000 m that was accompanied by a significant increase in brain water content (BWC). Moreover, observations of brain lipid oxidative damage and oxidative stress during the early stage of AHH exposure revealed DNA and cellular damage in cortical and hippocampal regions. Transcriptome profiling of the hippocampus revealed upregulation of forkhead box transcription factors. Similarly, western blot assays revealed upregulation of FOXO1a, FOXO3a, caspase-3 and Bax, and downregulation of Bcl-2, indicating a temporal influence of AHH on mitochondrial function and neuronal apoptosis. Thus, we found that the pathophysiology of HACE occurred with dynamic CBF changes, which triggered oxidative stress and neuronal damage in the mouse brain after AHH exposure. Our findings provide potential strategies for treatment of AHH in the future.
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Doença da Altitude , Edema Encefálico , Altitude , Animais , Circulação Cerebrovascular/fisiologia , Hipóxia , CamundongosRESUMO
Organophosphate (OP) compounds are widely used in agriculture, industry, and even terrorism. It is important to distinguish high-toxicity OP compounds from low-toxicity OP compounds in dealing with chemical accidents. However, there are very few portable and simple detection methods. Mesoporous silica gated switches may provide an effective solution. In this study, a gated switch based on mesoporous silica as an inorganic scaffold loaded with sulforhodamine B and capped with acetylcholinesterase (AChE) was prepared for specific detection of OP compounds. Carbamate derivatives (G1-G6) were designed and synthetized as grafting compounds in consideration of the binding ability with AChE. Through further modification and optimization, grafting compound G6 with phenylpyridine as the substituent showed the best capping capacity, and it achieved excellent blocking of mesoporous silica gated switches for loaded sulforhodamine B. In the presence of high-toxicity OP compounds, low-toxicity OP compounds, AChE substrates and reversible AChE inhibitors respectively, only high-toxicity OP compounds could make the gated switch release loaded sulforhodamine B. The limit of detection for paraoxon-ethyl was 10.6 µΜ. Furthermore, the preparation process of the gated switch is fast and simple, and the prepared gated switch has good stability and rapid distinguishing ability. The results of this paper provide a new idea for rapidly distinguishing high-toxicity OP compounds from low-toxicity OP compounds and other related compounds on the spot.
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Acetilcolinesterase , Organofosfatos , Acetilcolinesterase/química , Carbamatos , Inibidores da Colinesterase/química , Inibidores da Colinesterase/toxicidade , Organofosfatos/toxicidade , Dióxido de Silício/químicaRESUMO
lncRNAs, a group of eukaryotic cell genome-encoded transcripts, have been demonstrated to exert a notable impact on tumorigenesis. LINC01535, belonging to the lncRNA family, was reported to have an aberrant expression in certain types of cancers and thus affect cancer progression. Nevertheless, the expression pattern and potential roles of LINC01535 in clear cell renal cell carcinoma (ccRCC) remain to be elucidated. Here, LINC01535 expression was detected in ccRCC by RT-qPCR, cell proliferation by CCK-8 assays, and invasion by transwell assays. Besides, effects of LINC01535 on in vivo tumor growth were investigated by xenograft tumor models. The miR-146b-5p/LINC01535/TRIM2 interaction was evaluated via luciferase reporter assays. This study showed downregulation of LINC01535 in ccRCC. Moreover, LINC01535 upregulation attenuated in vitro ccRCC development and hindered in vivo tumor growth. Furthermore, LINC01535 sponged miR-146b-5p which had a negative correlation with LINC01535, and TRIM2 was a direct target of miR-146b-5p and mediated by LINC01535. Mechanically, LINC01535/miR-146b-5p/TRIM2 axis affected ccRCC progression by mediating the PI3K/Akt signaling. All in all, our observations suggest the LINC01535/miR-146b-5p/TRIM2 axis as a crucial role in ccRCC.
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BACKGROUND AND OBJECTIVE: Acyclovir is effective in treating herpes simplex virus infections of the central nervous system. The purpose of this study was to investigate the interactions between acyclovir and the efflux pumps P-glycoprotein (P-gp), breast cancer resistance protein (Bcrp), multidrug resistance protein 2 (Mrp2), and organic anion transporter 3 (Oat3) at the blood-brain barrier (BBB). METHODS: Acyclovir concentrations in the blood and brain were evaluated by microdialysis and high-performance liquid chromatography. Acyclovir pharmacokinetic parameters, including the area under the unbound blood concentration-time curve (AUCu,blood), the area under the unbound brain concentration-time curve (AUCu,brain), and the ratio of AUCu,brain to AUCu,blood (Kp.uu.brain), were evaluated in the presence and absence of elacridar (P-gp/Bcrp inhibitor, 7.5 mg/kg), tariquidar (P-gp/Bcrp inhibitor, 7.5 mg/kg), MK571 (Mrp2 inhibitor, 7.5 mg/kg), cyclosporine (P-gp/Bcrp/Mrp2 inhibitor, 25 mg/kg), and probenecid (Oat3 inhibitor, 50 mg/kg). RESULTS: The average AUCu,blood, AUCu,brain, and Kp.uu.brain in rats who received acyclovir (25 mg/kg, intravenous) alone were 1377.7 min · µg/ml, 435.4 min · µg/ml, and 31.6%, respectively. Probenecid drastically increased the AUCu,blood of acyclovir 1.73-fold, whereas coadministration with elacridar, tariquidar, MK571, and cyclosporine did not alter the blood pharmacokinetic parameters of acyclovir. Elacridar, tariquidar, MK571, cyclosporine, and probenecid significantly increased the AUCu,brain of acyclovir 1.51-, 1.54-, 1.47-, 1.95-, and 2.34-fold, respectively. Additionally, the Kp.uu.brain of acyclovir markedly increased 1.48-, 1.63-, 1.39-, 1.90-, and 1.35-fold following elacridar, tariquidar, MK571, cyclosporine, and probenecid administration, respectively. CONCLUSION: The present study demonstrated that P-gp, Bcrp, Mrp2, and Oat3 inhibition increased the penetration of acyclovir across the BBB, supporting the hypothesis that these efflux pumps restrict the distribution of acyclovir in the brain.
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Aciclovir , Barreira Hematoencefálica , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Transporte Biológico/fisiologia , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Proteínas de Neoplasias , Ratos , Membro 4 da Subfamília B de Transportadores de Cassetes de Ligação de ATPAssuntos
Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Junção Esofagogástrica/cirurgia , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Imunidade , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Gástricas/patologiaRESUMO
Recent studies indicate that inhibition of the efflux transporter P-glycoprotein (P-gp) at the blood-brain barrier (BBB) may represent a putative strategy to increase the BBB penetration of several antibiotics. Therefore, the present study aimed to investigate the effect of P-gp inhibition on the transport of ceftriaxone (CFX) across the BBB. Blood and brain microdialysis in rats was used to monitor blood and brain unbound CFX concentrations following intravenous administration (50 mg/kg), with or without pretreatment with one of the P-gp inhibitors, cyclosporin A (6.25, 12.5, 25 mg/kg) or verapamil (5, 10, 20 mg/kg). An inhibitory effect was demonstrated by an increase in the ratio of unbound brain to unbound blood concentration (Kp.uu.brain) of CFX. The concentrations of CFX in blood and brain from 0 to 180 min after intravenous administration (CFX, 50 mg/kg) ranged from 3 to 40 µg/ml and 1 to 10 µg/ml, respectively. The Kp.uu.brain of CFX was 24.74 ± 1.34%. Pretreatment with cyclosporin A increased the brain concentration and the Kp.uu.brain of CFX in a dose-dependent manner. However, pretreatment with verapamil increased the brain concentration of CFX but not the Kp.uu.brain. The present data shows that CFX might be a substrate of P-gp efflux transporter at the BBB and P-gp inhibition might enhance the brain concentration of CFX. Future studies involving more selective P-gp inhibitors or knockout mouse models should be conducted to specifically elucidate the impact of P-gp inhibition on penetration of CFX across the BBB.
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Barreira Hematoencefálica , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Animais , Transporte Biológico/fisiologia , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Ceftriaxona/farmacologia , Camundongos , RatosRESUMO
As a natural heme protein catalyzing the oxidation of sulfides to sulfoxides without sulfone formation, chloroperoxidase (CPO) is well suited for the degradation of sulfur mustard (HD), a persistent chemical warfare agent that has been widely disposed since World War II and continuously leaks into aquatic environments. Herein, we report the first systematic investigation of CPO-catalyzed degradation of HD and the potential application of CPO in destroying chemical weapons under mild conditions. The related Michaelis-Menten parameters (Km=0.17 mM, Vmax=0.06 mM s-1 (R2 =0.935), and kcat= 2717 s-1) indicated nearly a prominent enzymatic efficiency. Under optimal conditions, 80% of HD was transformed to bis(2-chloroethyl) sulfoxide as identified by mass spectroscopy and nuclear magnetic resonance (NMR) spectroscopy. Other metabolites were also generated during the decontamination process. A plausible oxidation mechanism was proposed based on the degradation products, NMR titration experiments, and molecular dynamics simulations. CPO also promoted the degradation of other chemical weapon agents, namely, Lewisite (L) and venomous agent X (VX), thereby exhibiting a broad substrate scope. The high potential of the developed system for the decontamination of aquatic environments was demonstrated by the successful hatching of zebrafish embryos after HD degradation and the survival of zebrafish (Danio rerio, AB strain) larvae after the degradation of Agent Yellow (L+HD).
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Cloreto Peroxidase , Gás de Mostarda , Animais , Catálise , Gás de Mostarda/toxicidade , Estresse Oxidativo , Peixe-Zebra/metabolismoRESUMO
A fluorescent probe was developed for ratiometric detection of thallium ions in mineral water samples by modifying a G-rich aptamer (PS2.M - 7) with a fluorescence donor (Cyanine-3, Cy3) and a quencher (Cyanine-5, Cy5). The probe had a random coil structure that changed into a G-quadruplex structure upon binding with Tl+. This change in structure decreased the distance between the donor and acceptor moieties, which resulted in fluorescence resonance energy transfer between Cy3 and Cy5. Under optimized conditions, the limit of detection and linear concentration range for Tl+ were 30.1 µM (3σ) and 10 µM-10 mM (R2 = 0.9981), respectively. This simple and cost-effective fluorescence sensor provided satisfactory results for detection of thallium ions in spiked mineral water samples.
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Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Quadruplex G , Transferência Ressonante de Energia de Fluorescência , Limite de Detecção , TálioRESUMO
Dermatomyositis (DM) is an idiopathic inflammatory myopathy that is closely related to malignant diseases. Our study aims to investigate the incidence and predictive factors for occurrence of malignancy among DM patients from Central China.We performed a retrospective, paired, case-control study of 736 DM patients admitted to the First Affiliated Hospital of Zhengzhou University between 2010 and 2017. We paired the 65 patients with malignancy with age-matched and sex-matched patients without malignancy in a ratio of 1:2. Two hundred two patients were finally enrolled and their clinical and laboratory data were collected.The incidence of malignancy in DM patients was 8.83% (65/736). Most malignancies were detected in the most recent 1 year before (9/65, 13.85%) or within 3 years after (40/65, 61.54%) the onset of DM. Males (35/65, 53.85%) and patients aged between 50 and 69 years (43/65, 66.15%) were prone to develop malignancies. Lung cancer (nâ=â11, 31.43%) was the most common malignancy in male patients, while for females, thyroid, breast and cervical cancer (nâ=â4 each, 13.33%) were more prevalent. Adenocarcinoma and squamous cell carcinoma (both 18/65, 27.69%) were the top two most common pathological types. Univariate analysis demonstrated that Gottron's sign (Pâ=â.02), dysphagia (Pâ=â.04), albumin (ALB) reduction (Pâ=â.003), aspartate aminotransferase (AST, Pâ=â.03), creatine kinase-MB (Pâ=â.02), absence of fever (Pâ=â.02), arthralgia (Pâ=â.04) and interstitial lung disease (ILD, Pâ=â.05) were closely related to the occurrence of malignancy. Multivariate analysis revealed the independent risk factors of ALB reduction (odds ratioâ=â1.546, Pâ=â.04) and the protective factor of ILD (odds ratioâ=â0.349, Pâ=â.003). There was no significant difference in the follow-up period between patients with and without ILD (Pâ=â.38).ALB reduction and the absence of ILD were the risk factors for malignancy in DM patients. The protective mechanism of ILD for DM patients needs further study.
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Dermatomiosite/epidemiologia , Neoplasias/epidemiologia , Fatores Etários , Idade de Início , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Neoplasias/patologia , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fatores de TempoRESUMO
Cyclin-dependent kinase 5 (Cdk5) is a regulator of axon growth and radial neuronal migration in the developing mouse brain, and it plays critical roles in cortical structure formation and brain function. However, the function of Cdk5 in cortico-cortical and cortico-sensorimotor networks in the adult remains largely unknown. In this study, we investigated the function of Cdk5 in the rostral secondary motor cortex (M2) in the male mouse using CRISPR/Cas9 gene editing and somatic brain transgenesis, to produce M2-specific knockdown of Cdk5 in neurons in the male mouse. Mouse deficient in Cdk5 in the M2 exhibited a reduction in both the number of functional synapses and the total basal dendritic length, as well as motor dysfunction. Furthermore, whole-cell patch-clamp recordings in layer V green fluorescent protein (GFP)-tag pyramidal neurons revealed a decrease in the frequency and amplitude of miniature EPSCs and miniature IPSCs, as well as a reduction in the population synaptic responses (fEPSPs) in these mice. Specifically, retrograde labeling showed that Cdk5 knockdown in the M2 caused a reduction in long-range projections to the M2 from the thalamus/prefrontal cortex and claustrum. Collectively, our findings show a new regulatory role of Cdk5 in neural circuit maintenance, and that the changes in neural transmission and circuits in the mice with Cdk5 knockdown in the M2 likely contribute to the motor dysfunction in these animals.
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Quinase 5 Dependente de Ciclina , Córtex Motor , Animais , Quinase 5 Dependente de Ciclina/genética , Quinase 5 Dependente de Ciclina/metabolismo , Masculino , Camundongos , Córtex Motor/metabolismo , Neurônios/metabolismo , Células Piramidais/metabolismo , Transmissão SinápticaRESUMO
The simultaneous detection of K+ and Tl+ can serve as a toxicological diagnostic tool for thallium poisoning. Colorimetric-reaction-based nanoprobes have emerged as promising sensors for the rapid and ultrasensitive detection of molecular species in simple systems. However, the development of viable screening tools for multicomponent analysis in complex systems remains challenging owing to interference from coexisting materials in the media. Herein, a simple chemical sensor array based on the peroxidase-like activity of gold nanoparticles modified with single-stranded DNA (AuNPs-ssDNA) and chemometrics was developed for the simultaneous detection of K+ and Tl+ in aqueous solutions and serum. The use of a K+ adapter conferred high selectivity to the developed method. Optimized AuNPs-ssDNAs were used to construct a sensor array, which together with chemometrics provided fingerprints that can facilitate the simultaneous analysis of multiple components. The developed colorimetric reaction in combination with the chemometrics assay was directly used as a biosensor array, which exhibited detection limits of 107.33 nM for K+ and 19.26 nM for Tl+. The developed method could potentially serve as a diagnostic technique for investigating thallium poisoning and toxicology.
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Água Potável/análise , Potássio/análise , Tálio/análise , Técnicas Biossensoriais/métodos , Colorimetria/métodos , DNA de Cadeia Simples/química , Ouro/química , Humanos , Nanopartículas Metálicas/química , Potássio/sangue , Espectrofotometria Ultravioleta/métodos , Tálio/sangueRESUMO
The detection of psychoactive substances is an important branch of modern analytical chemistry and has many legally and socially relevant implications. The use of a surface plasmon resonance (SPR)-based gene-nanoparticle system has emerged as a promising technique for the rapid and ultrasensitive detection of molecular species such as drugs of abuse in biofluids. However, the development of a viable screening tool for the detection of multiple classes of drugs in complex media is a considerable challenge because the existing techniques lack affinity toward certain species due to matrix interference. Our aim was to develop a simple optical sensor array for the classification of nine narcotic drugs in aqueous solution and human urine. The UV-vis spectra of DNA-gold nanoparticles in the presence of nine narcotic drugs (pentobarbital sodium, caffeine, morphine, remifentanil, fentanyl, ketamine, etomidate, carfentanil, and sulfentanyl) were distinctly different. Furthermore, the narcotic drugs present in aqueous solution and in human urine were classified correctly through partial least squares discriminant analysis (PLS-DA). Combination with a multi-sensor unit further improved the prediction accuracy of the PLS-DA models. The proposed method has potential for on-site drug detection and drug abuse screening.
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Técnicas de Química Analítica , Nanotecnologia/métodos , Entorpecentes/urina , Detecção do Abuso de Substâncias/métodos , Análise Discriminante , Ouro/química , Humanos , Nanopartículas Metálicas/química , Espectrofotometria Ultravioleta , Ressonância de Plasmônio de Superfície/métodosRESUMO
A wide range of metals exhibit anomalous electrical and thermodynamic properties when tuned to a quantum critical point (QCP), although the origins of such strange metals have posed a long-standing mystery. The frequent association of strange metals with unconventional superconductivity and antiferromagnetic QCPs1-4 has led to the belief that they are highly entangled quantum states5. By contrast, ferromagnets are regarded as an unlikely setting for strange metals, because they are weakly entangled and their QCPs are often interrupted by competing phases or first-order phase transitions6-8. Here we provide evidence that the pure ferromagnetic Kondo lattice9,10 CeRh6Ge4 becomes a strange metal at a pressure-induced QCP. Measurements of the specific heat and resistivity under pressure demonstrate that the ferromagnetic transition is continuously suppressed to zero temperature, revealing a strange-metal behaviour around the QCP. We argue that strong magnetic anisotropy has a key role in this process, injecting entanglement in the form of triplet resonating valence bonds into the ordered ferromagnet. We show that a singular transformation in the patterns of the entanglement between local moments and conduction electrons, from triplet resonating valence bonds to Kondo-entangled singlet pairs at the QCP, causes a jump in the Fermi surface volume-a key driver of strange-metallic behaviour. Our results open up a direction for research into ferromagnetic quantum criticality and establish an alternative setting for the strange-metal phenomenon. Most importantly, strange-metal behaviour at a ferromagnetic QCP suggests that quantum entanglement-not the destruction of antiferromagnetism-is the common driver of the varied behaviours of strange metals.
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Rapid and precise detection of Tl+ and Pb2+ is important to prevent water poisoning and environmental pollution. Gold nanoparticles (AuNPs) have gained focus for heavy metal ion detection but cannot yet achieve accurate quantitative analyses when Tl+ and Pb2+ coexist. We propose a sensitive, flexible, and low-cost method for the qualitative and quantitative analysis of binary Tl+/Pb2+ mixtures based on AuNP sensors. Partial least squares, back interval partial least squares and data fusion applied to analyze UV-Vis spectral data according to the AuNPs aggregation behavior, revealed discrete responses to the target analytes. The limits of detection for Tl+ and Pb2+ in the binary mixture were 5.23 and 1.76 nM, respectively, and good linear dependence was obtained. The method was successfully applied to the detection of both ions in tap and mineral water. This method can reveal water poisoning and environmental pollution events to ensure drinking water safety.
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Água Potável/química , Chumbo/análise , Nanopartículas Metálicas/química , Tálio/análise , Cátions/química , OuroRESUMO
OBJECTIVE: To determine thallium in whole blood by atomic absorption detection method, and to investigate the eliminating effect of hemoperfusion (HP) for thallium in blood. METHODS: The blood of Beagle dogs which had not exposed to thallium before were obtained for preparation of thallium nitrate ( TlNO3 )-containing solution in three concentrations according to the conversion formula based on animal weight and volume of blood. HP was performed in the simulated in vivo environment. The content of TlNO3 in blood of the next group was determined on the amount of TlNO3 for the last HP of the former dose group. Thallium quantity in different samples was measured with atomic absorption spectrometer blood samples before and after HP. Finally, the thallium concentration in blood was analyzed statistically. RESULTS: Thallium concentrations showed a good linear relationship in the range of 0-200 µg/L (r = 0.998 4). The intra-day precision (RSD) was lower than 4.913%, the intra-day recovery rate was 96.2%-111.9%; the inter-day precision (RSD) was lower than 7.502%, the inter-day recovery rate was 89.6%-105.2%. The concentration of thallium in blood was significantly reduced after HP per time in high, middle, and low dose groups [(453.43 ± 27.80) mg/L to (56.09 ± 14.44) mg/L in high dose group, F = 8.820, P = 0.003; (64.51 ± 13.60) mg/L to (3.19 ± 0.23) mg/L in middle dose group, F = 36.312, P = 0.000; (5.40 ± 0.98) mg/L to (0.38 ± 0.25) mg/L in low dose group, F = 46.240, P = 0.000 ]. The adsorption rate of four times of HP in high, middle and low dose group were (87.63 ± 2.48 )%, (95.06 ± 1.54 )% and (92.76 ± 4.87)%, respectively, without significant difference (F = 4.231, P = 0.070). CONCLUSIONS: The method for measuring thallium was established, and it shows a very stable, simple, sensitive for determination of thallium. HP can effectively remove thallium from blood. Thallium concentration can be reduced by 90% after four times of HP. HP is also effective even when thallium concentration is not high.
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Hemoperfusão , Espectrofotometria Atômica , Animais , Cães , TálioRESUMO
A new isotope-dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of sulfur mustard (SM) has been developed using a direct chemical derivatization method by nucleophile potassium thioacetate (PTA) in aqueous solution. The reaction conditions for derivatization, such as reaction temperature, time, solvent and concentration of PTA, were optimized for high performance. Reversed phase liquid chromatography was suitable for analysis of such a PTA derivatized SM in complex environmental samples. Compared with other conventional gas chromatography or gas chromatography-mass spectrometry methods for direct detection on SM, better sensitivity and selectivity were achieved by this direct derivatization and LC-MS/MS method, where SM can be detected as low as 0.05 ng/mL in acetonitrile. The linear range was from 0.1 to 1000 ng/mL. The relative standard deviation (RSD) of the intra-day precision was less than 11.8%, and RSD of the inter-day precision was less than 12.3%. The whole procedure for both derivatization and analysis was quick and simple, and the total time was less than 1h. This established method has been successfully employed for determination of spiking samples both in water and soil. A detection limit of 0.1 ng/mL was achieved for river water, while the SM in soil sample could be detected at 0.1 ng/g.