RESUMEN
α7 nicotinic acetylcholine receptors (nAChRs) are mainly distributed in the central nervous system (CNS), including the hippocampus, striatum, and cortex of the brain. The α7 nAChR has high Ca2+ permeability and can be quickly activated and desensitized, and is closely related to Alzheimer's disease (AD), epilepsy, schizophrenia, lung cancer, Parkinson's disease (PD), inflammation, and other diseases. α-conotoxins from marine cone snail venom are typically short, disulfide-rich neuropeptides targeting nAChRs and can distinguish various subtypes, providing vital pharmacological tools for the functional research of nAChRs. [Q1G, ΔR14]LvΙB is a rat α7 nAChRs selective antagonist, modified from α-conotoxin LvΙB. In this study, we utilized three types of fluorescein after N-Hydroxy succinimide (NHS) activation treatment: 6-TAMRA-SE, Cy3 NHS, and BODIPY-FL NHS, labeling the N-Terminal of [Q1G, ΔR14]LvΙB under weak alkaline conditions, obtaining three fluorescent analogs: LvIB-R, LvIB-C, and LvIB-B, respectively. The potency of [Q1G, ΔR14]LvΙB fluorescent analogs was evaluated at rat α7 nAChRs expressed in Xenopus laevis oocytes. Using a two-electrode voltage clamp (TEVC), the half-maximal inhibitory concentration (IC50) values of LvIB-R, LvIB-C, and LvIB-B were 643.3 nM, 298.0 nM, and 186.9 nM, respectively. The stability of cerebrospinal fluid analysis showed that after incubation for 12 h, the retention rates of the three fluorescent analogs were 52.2%, 22.1%, and 0%, respectively. [Q1G, ΔR14]LvΙB fluorescent analogs were applied to explore the distribution of α7 nAChRs in the hippocampus and striatum of rat brain tissue and it was found that Cy3- and BODIPY FL-labeled [Q1G, ΔR14]LvΙB exhibited better imaging characteristics than 6-TAMARA-. It was also found that α7 nAChRs are widely distributed in the cerebral cortex and cerebellar lobules. Taking into account potency, imaging, and stability, [Q1G, ΔR14]LvΙB -BODIPY FL is an ideal pharmacological tool to investigate the tissue distribution and function of α7 nAChRs. Our findings not only provide a foundation for the development of conotoxins as visual pharmacological probes, but also demonstrate the distribution of α7 nAChRs in the rat brain.
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Encéfalo , Conotoxinas , Xenopus laevis , Receptor Nicotínico de Acetilcolina alfa 7 , Animales , Receptor Nicotínico de Acetilcolina alfa 7/metabolismo , Conotoxinas/farmacología , Conotoxinas/química , Ratas , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Oocitos/efectos de los fármacos , Oocitos/metabolismo , Antagonistas Nicotínicos/farmacología , Colorantes Fluorescentes , Ratas Sprague-Dawley , Masculino , FemeninoRESUMEN
α6ß4* nicotinic acetylcholine receptor (nAChR) (* represents the possible presence of additional subunits) is mainly distributed in the central and peripheral nervous system and is associated with neurological diseases, such as neuropathic pain; however, the ability to explore its function and distribution is limited due to the lack of pharmacological tools. As one of the analogs of α-conotoxin (α-CTx) LvIC from Conus lividus, [D1G, Δ14Q]LvIC (Lv) selectively and potently blocks α6/α3ß4 nAChR (α6/α3 represents a chimera). Here, we synthesized three fluorescent analogs of Lv by connecting fluorescent molecules 6-carboxytetramethylrhodamine succinimidyl ester (6-TAMRA-SE, R), Cy3 NHS ester (Cy3, C) and BODIPY-FL NHS ester (BDP, B) to the N-terminus of the peptide and obtained Lv-R, Lv-C, and Lv-B, respectively. The potency and selectivity of three fluorescent peptides were evaluated using two-electrode voltage-clamp recording on nAChR subtypes expressed in Xenopus laevis oocytes, and the potency and selectivity of Lv-B were almost maintained with the half-maximal inhibition (IC50) of 64 nM. Then, we explored the stability of Lv-B in artificial cerebrospinal fluid and stained rat brain slices with Lv-B. The results indicated that the stability of Lv-B was slightly improved compared to that of native Lv. Additionally, we detected the distribution of the α6ß4* nAChR subtype in the cerebral cortex using green fluorescently labeled peptide and fluorescence microscopy. Our findings not only provide a visualized pharmacological tool for exploring the distribution of the α6ß4* nAChR subtype in various situ tissues and organs but also extend the application of α-CTx [D1G, Δ14Q]LvIC to demonstrate the involvement of α6ß4 nAChR function in pathophysiology and pharmacology.
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Conotoxinas , Caracol Conus , Receptores Nicotínicos , Ratas , Animales , Receptores Nicotínicos/química , Conotoxinas/química , Conotoxinas/farmacología , Caracol Conus/química , Péptidos/química , ÉsteresRESUMEN
α4/6-conotoxin TxID, which was identified from Conus textile, simultaneously blocks rat (r) α3ß4 and rα6/α3ß4 nicotinic acetylcholine receptors (nAChRs) with IC50 values of 3.6 nM and 33.9 nM, respectively. In order to identify the effects of loop2 size on the potency of TxID, alanine (Ala) insertion and truncation mutants were designed and synthesized in this study. An electrophysiological assay was used to evaluate the activity of TxID and its loop2-modified mutants. The results showed that the inhibition of 4/7-subfamily mutants [+9A]TxID, [+10A]TxID, [+14A]TxID, and all the 4/5-subfamily mutants against rα3ß4 and rα6/α3ß4 nAChRs decreased. Overall, ala-insertion or truncation of the 9th, 10th, and 11th amino acid results in a loss of inhibition and the truncation of loop2 has more obvious impacts on its functions. Our findings have strengthened the understanding of α-conotoxin, provided guidance for further modifications, and offered a perspective for future studies on the molecular mechanism of the interaction between α-conotoxins and nAChRs.
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Conotoxinas , Caracol Conus , Receptores Nicotínicos , Ratas , Animales , Conotoxinas/química , Caracol Conus/química , Receptores Nicotínicos/metabolismo , Alanina , Antagonistas Nicotínicos/farmacología , Antagonistas Nicotínicos/químicaRESUMEN
Heavy metal pollution, including that caused by cadmium (Cd), is a matter of increasing concern. Although in situ passivation remediation has been widely used to treat heavy metal-polluted soils, most studies have focused on acidic soils, while studies on alkaline soil conditions are scarce. In this study, the effects of biochar (BC), phosphate rock powder (PRP), and humic acid (HA) on Cd2+ adsorption were examined alone and in combination to choose an appropriate Cd passivation approach for weakly alkaline soils. Additionally, the combined impact of passivation on Cd availability, plant Cd absorption, plant physiology indexes, and soil microbial community was elucidated. BC had a higher Cd adsorption capacity and removal rate than those of PRP and HA. Moreover, HA and PRP enhanced the adsorption capacity of BC. A combination of biochar and humic acid (BHA), and biochar and phosphate rock powder (BPRP) significantly affected soil Cd passivation. BHA and BPRP decreased the plant Cd content and soil Cd-DTPA (diethylenetriaminepentaacetic acid) by 31.36 %, 20.80 %, 38.19 %, and 41.26 %, respectively; however, they increased the fresh weight by 65.64-71.48 % respectively, and dry weight by 62.41-71.35 %, respectively. Notably, only BPRP increased the node and root tip number in wheat. Total protein (TP) content increased in BHA and BPRP, with BHA showing lower TP than BPRP. BHA and BPRP showed a reduction in glutathione (GSH), malondialdehyde (MDA), H2O2, and peroxidase (POD); BHA showed a significantly lower GSH than BPRP. Additionally, BHA and BPRP increased soil sucrase, alkaline phosphatase, and urease activities, with BPRP showing considerably higher enzyme activity than BHA. Both BHA and BPRP increased the number of soil bacteria, altered the community composition, and critical metabolic pathways. The results demonstrated that BPRP could be used as a highly effective, novel passivation technique for the remediation of Cd-contaminated soil.
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Metales Pesados , Contaminantes del Suelo , Cadmio/análisis , Suelo , Sustancias Húmicas , Peróxido de Hidrógeno , Polvos , Contaminantes del Suelo/análisis , Metales Pesados/análisis , Carbón Orgánico , FosfatosRESUMEN
Conotoxins are widely distributed and important for studying ligand-gated ion channels. TxIB, a conotoxin consisting of 16 amino acids derived from Conus textile, is a unique selective ligand that blocks rat α6/α3ß2ß3 nAChR (IC50 = 28 nM) without affecting other rat subtypes. However, when the activity of TxIB against human nAChRs was examined, it was unexpectedly found that TxIB had a significant blocking effect on not only human α6/α3ß2ß3 nAChR but also human α6/α3ß4 nAChR, with an IC50 of 537 nM. To investigate the molecular mechanism of this species specificity and to establish a theoretical basis for drug development studies of TxIB and its analogs, different amino acid residues between human and rat α6/α3 and ß4 nAChR subunits were identified. Each residue of the human species was then substituted with the corresponding residue of the rat species via PCR-directed mutagenesis. The potencies of TxIB towards the native α6/α3ß4 nAChRs and their mutants were evaluated through electrophysiological experiments. The results showed that the IC50 of TxIB against h[α6V32L, K61R/α3]ß4L107V, V115I was 22.5 µM, a 42-fold decrease in potency compared to the native hα6/α3ß4 nAChR. Val-32 and Lys-61 in the human α6/α3 subunit and Leu-107 and Val-115 in the human ß4 subunit, together, were found to determine the species differences in the α6/α3ß4 nAChR. These results also demonstrate that the effects of species differences between humans and rats should be fully considered when evaluating the efficacy of drug candidates targeting nAChRs in rodent models.
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Conotoxinas , Caracol Conus , Receptores Nicotínicos , Ratas , Humanos , Animales , Especificidad de la Especie , Conotoxinas/farmacología , Conotoxinas/química , Caracol Conus/química , Reacción en Cadena de la Polimerasa , Receptores Nicotínicos/metabolismoRESUMEN
Dissolved organic matter (DOM) has been known to inhibit the degradation of trace organic contaminants (TrOCs) in advanced oxidation processes but quantitative understanding is lacking. Adenine (ADN) was selected as a model TrOC due to the wide occurrence of purine groups in TrOCs and the well-documented transient spectra of its intermediate radicals. ADN degradation in the presence of DOM during UV/peroxydisulfate treatment was quantified using steady-state photochemical experiments, time-resolved spectroscopy, and kinetic modeling. The inhibitory effects of DOM were found to include competing for photons, scavenging SO4â¢- and HOâ¢, and also converting intermediate ADN radicals (ADN(-H)â¢) back into ADN. Half of the ADN(-H)⢠were reduced back to ADN in the presence of about 0.2 mgC L-1 of DOM. The quenching rate constants of ADN(-H)⢠by the 10 tested DOM isolates were in the range of (0.39-1.18) × 107 MC-1 s-1. They showed a positive linear relationship with the total antioxidant capacity of DOM. The laser flash photolysis results of the low-molecular-weight analogues of redox-active moieties further supported the dominant role of antioxidant moieties in DOM in the quenching of ADN(-H)â¢. The diverse roles of DOM should be considered in predicting the abatement of TrOCs in advanced oxidation processes.
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Antioxidantes , Contaminantes Químicos del Agua , Materia Orgánica Disuelta , Oxidación-Reducción , Fotólisis , Purinas , Contaminantes Químicos del Agua/químicaRESUMEN
Recently, there has been increasing concern about the health hazards of heavy metal-polluted farmlands. Recent findings suggest that intercropping could be effective remediation strategy for agricultural soils without affecting crop biomass yield. However, there are concerns on the heavy metal accumulation in plant organs in phytoremediation, emphasizing the need to develop an effective intercropping remediation model. In this study, we evaluated the effects of intercropping rape and wheat with different accumulation characteristics of cadmium (Cd), and crop growth and physiological characteristics. Intercropping significantly reduced the Cd content of rape shoot and root, with the rape-low Cd-accumulating wheat intercropping system yielding the best results. However, intercropping had no significant effect on Cd accumulation in wheat. Additionally, intercropping affected the root system configuration and structure, photosynthetic indicators, chlorophyll content, crop enzyme content, and rhizosphere enzyme activity of both species, but did not significantly affect the biomass of wheat and rape. Overall, our findings showed that intercropping rape with a low Cd-accumulating wheat variety could be an effective model for safe production of wheat and rape in weak alkaline soils without compromising biomass yield. The study demonstrates that similar innovative, effective, and judicious intercropping strategy can enrich the theory of contaminated soil remediation.
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Violación , Triticum , Cadmio , Suelo , BiomasaRESUMEN
Timely and accurate identification of fault types at the early stage of minor faults is significant for cutting off fault evolution. In order to have a clear understanding of the pipeline robot's own situation in the pipeline, this paper proposes a fault diagnosis system for pipeline robots based on sound signal recognition. This can effectively reduce the probability of serious faults such as shutdown and loss of control in the pipeline without affecting the safe operation of the pipeline robot, which is a key issue to improve the reliability of the pipeline robot. The system consists of a combination of three parts: hardware, software, and algorithm. On the one hand, Raspberry Pi is the core module, while on the other hand, it is also responsible for the data transmission between the various modules, including storing the original sound signals collected by the sensors and transmitting the diagnosis results to the upper computer software interface. The proposed system is validated on the dataset collected by the data experimentation platform. The experimental results show that the proposed fault prediction method obtains advanced results on this dataset, verifying the effectiveness and stability of the proposed fault diagnosis system for pipeline robots based on sound signal recognition.
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Robótica , Algoritmos , Reproducibilidad de los Resultados , Robótica/métodos , Programas Informáticos , SonidoRESUMEN
Nicotinic acetylcholine receptor (nAChR), a member of pentameric ligand-gated ion channel transmembrane protein composed of five subunits, is widely distributed in the central and peripheral nervous system. The nAChRs are associated with various neurological diseases, including schizophrenia, Alzheimer's disease, Parkinson's disease, epilepsy and neuralgia. Receptors containing the α3 subunit are associated with analgesia, generating our interest in their role in pharmacological studies. In this study, α-conotoxin (α-CTx) LvIF was identified as a 16 amino acid peptide using a genomic DNA clone of Conus lividus (C. lividus). The mature LvIF with natural structure was synthesized by a two-step oxidation method. The blocking potency of α-CTx lvIF on nAChR was detected by a two-electrode voltage clamp. Our results showed that α-CTx LvIF was highly potent against rα3ß2 and rα6/α3ß2ß3 nAChR subtypes, The half-maximal inhibitory concentration (IC50) values of α-CTx LvIF against rα3ß2 and rα6/α3ß2ß3 nAChRs expressed in Xenopus oocytes were 8.9 nM and 14.4 nM, respectively. Furthermore, α-CTx LvIF exhibited no obvious inhibition on other nAChR subtypes. Meanwhile, we also conducted a competitive binding experiment between α-CTxs MII and LvIF, which showed that α-CTxs LvIF and MII bind with rα3ß2 nAChR at the partial overlapping domain. These results indicate that the α-CTx LvIF has high potential as a new candidate tool for the studying of rα3ß2 nAChR related neurophysiology and pharmacology.
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Conotoxinas/farmacología , Caracol Conus , Antagonistas Nicotínicos/farmacología , Receptores Nicotínicos/metabolismo , Animales , Conotoxinas/química , Antagonistas Nicotínicos/químicaRESUMEN
Tobacco smoking has become a prominent health problem faced around the world. The α3ß4 nicotinic acetylcholine receptor (nAChR) is strongly associated with nicotine reward and withdrawal symptom. α-Conotoxin TxID, cloned from Conus textile, is a strong α3ß4 nAChR antagonist, which has weak inhibition activity of α6/α3ß4 nAChR. Meanwhile, its analogue [S9K]TxID only inhibits α3ß4 nAChR (IC50 = 6.9 nM), and has no inhibitory activity to other nAChRs. The present experiment investigates the effect of α3ß4 nAChR antagonists (TxID and [S9K]TxID) on the expression and reinstatement of nicotine-induced conditioned place preference (CPP) and explores the behaviors of acute nicotine in mice. The animal experimental results showed that TxID and [S9K] TxID could inhibit the expression and reinstatement of CPP, respectively. Moreover, both had no effect in acute nicotine experiment and the locomotor activity in mice. Therefore, these findings reveal that the α3ß4 nAChR may be a potential target for anti-nicotine addiction treatment. [S9K]TxID, α3ß4 nAChR antagonist, exhibit a superior effect for anti-nicotine addiction, which is promising to develop a novel smoking cessation drug.
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Condicionamiento Operante/efectos de los fármacos , Conotoxinas/farmacología , Nicotina/antagonistas & inhibidores , Nicotina/farmacología , Agonistas Nicotínicos/farmacología , Antagonistas Nicotínicos/farmacología , Animales , Conotoxinas/síntesis química , Masculino , Ratones , Ratones Endogámicos C57BL , Actividad Motora/efectos de los fármacos , Antagonistas Nicotínicos/síntesis química , Receptores Nicotínicos/efectos de los fármacosRESUMEN
Inductive transducers are widely applied to active magnetic bearings (AMBs). However, when the rotor rotates at a high speed, the rotor defects will affect the measuring signal (the magnetic field generated by transducer coils) and then reduce the transducer measuring accuracy. The rotor in AMBs is assembled with laminations, which will result in rotor non-mechanical errors. In this paper, rotor non-mechanical errors, including the anisotropic internal permeability and anisotropic surface conductivity, and their influence on double-pole variable-gap inductive transducers are explored in depth. The anisotropic internal permeability will affect the transducer measuring accuracy and bring about 1.3 ± 0.1 % measurement error. The anisotropic surface conductivity leads to different eddy currents around the rotor, influences the equivalent reluctance of the magnetic circuit, and then affectsthe transducer measuring accuracy. The experiments prove that rotor non-mechanical errors have a significant influence on transducer measurement accuracy, and the reduction of the transducer excitation frequency can reduce the measurement error and improve the AMB control performance.
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α-Conotoxin LvIA is derived from Conus lividus, native to Hainan, and is the most selective inhibitor of α3ß2 nicotinic acetylcholine receptors (nAChRs) known to date. In this study, an efficient approach for the production of recombinant α-Conotoxin LvIA is described. Tandem repeats of a LvIA gene fragment were constructed and fused with a KSI gene and a His6 tag in a Escherichia coli (E. coli) expression vector pET-31b(+). The recombinant plasmids were transformed into E. coli and were found to express well. The KSI-(LvIA)n-His6 fusion protein was purified by metal affinity chromatography and then cleaved with CNBr to release recombinant LvIA (rLvIA). High yields of fusion protein ranging from 100 to 500 mg/L culture were obtained. The pharmacological profile of rLvIA was determined by two-electrode voltage-clamp electrophysiology in Xenopus laevis oocytes expressing rat nAChR subtypes. The rLvIA antagonized the α3ß2 nAChR subtype selectively with a nano-molar IC50. The rLvIA was analgesic in a mouse hot-plate test model of pain. Overall, this study provides an effective method to synthesize α-conotoxin LvIA in an E. coli recombinant expression system, and this approach could be useful to obtain active conopeptides in large quantity and at low cost.
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Conotoxinas/química , Escherichia coli/química , Receptores Nicotínicos/metabolismo , Proteínas Recombinantes/química , Analgésicos/farmacología , Animales , Caracol Conus , Escherichia coli/metabolismo , Humanos , Concentración 50 Inhibidora , Ratones , Dimensión del Dolor , Ratas , Agua de Mar , Xenopus laevisRESUMEN
Cone snails express a sophisticated arsenal of small bioactive peptides known as conopeptides or conotoxins (CTxs). Through evolutionary selection, these peptides have gained the ability to interact with a range of ion channels and receptors, such as nicotinic acetylcholine receptors (nAChRs). Here, we used reversed-phase high performance liquid chromatography (RP-HPLC) and electrospray ionization-mass spectrometry (ESI-MS) to explore the venom peptide diversity of Conus textile, a species of cone snail native to Hainan, China. One fraction of C. textile crude venom potently blocked α3ß2 nAChRs. Subsequent purification, synthesis, and tandem mass spectrometric analysis demonstrated that the most active compound in this fraction was identical to α-CTx TxIA, an antagonist of α3ß2 nAChRs. Then three disulfide isoforms of α-CTx TxIA were synthesized and their activities were investigated systematically for the first time. As we observed, disulfide isomerisation was particularly important for α-CTx TxIA potency. Although both globular and ribbon isomers showed similar retention times in RP-HPLC, globular TxIA potently inhibited α3ß2 nAChRs with an IC50 of 5.4 nM, while ribbon TxIA had an IC50 of 430 nM. In contrast, beads isomer had little activity towards α3ß2 nAChRs. Two-step oxidation synthesis produced the highest yield of α-CTx TxIA native globular isomer, while a one-step production process based on random oxidation folding was not suitable. In summary, this study demonstrated the relationship between conotoxin activity and disulfide connectivity on α-CTx TxIA.
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Conotoxinas/farmacología , Cistina/química , Antagonistas Nicotínicos/farmacología , Animales , Células Cultivadas , Cromatografía Líquida de Alta Presión , Cromatografía de Fase Inversa , Conotoxinas/síntesis química , Conotoxinas/aislamiento & purificación , Caracol Conus/química , Potenciales de la Membrana/efectos de los fármacos , Antagonistas Nicotínicos/síntesis química , Antagonistas Nicotínicos/aislamiento & purificación , Ratas , Receptores Nicotínicos/metabolismo , Espectrometría de Masa por Ionización de Electrospray , Relación Estructura-Actividad , Xenopus laevisRESUMEN
The low current density impedes the practical application of microbial electrosynthesis for CO2 fixation. Engineering the reactor design is an effective way to increase the current density, especially for H2-mediated microbial electrosynthesis reactors. The electrolytic bubble column microbial electrosynthesis reactor has shown great potential for scaling up, but the mixing and gas mass transfer still need to be enhanced to further increase the current density. Here, we introduced an inner draft tube to the bubble column to tackle the problem. The addition of draft tube resulted in a 76.6% increase in the volumetric mass transfer coefficient (kLa) of H2, a 40% increase in the maximum current density (337 A/m2) and a 72% increase in average acetate production rate (3.1 g/L/d). The computational fluid dynamics simulations showed that the addition of draft tube enhanced mixing efficiency by enabling a more ordered cyclic flow pattern and a more uniform gas/liquid distribution. These results indicate that the electro-bubble column reactor with draft tube holds great potential for industrial implementation.
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Reactores Biológicos , Dióxido de Carbono , AcetatosRESUMEN
The two most active disulfide bond isomers of the analgesic αO-conotoxin GeXIVA, namely GeXIVA[1, 2] and GeXIVA[1, 4], were subjected to Asp-scanning mutagenesis to determine the key amino acid residues for activity at the rat α9α10 nicotinic acetylcholine receptor (nAChR). These studies revealed the key role of arginine residues for the activity of GeXIVA isomers towards the α9α10 nAChR. Based on these results, additional analogues with 2-4 mutations were designed and tested. The analogues [T1A,D14A,V28K]GeXIVA[1, 2] and [D14A,I23A,V28K]GeXIVA[1, 4] were developed and showed sub-nanomolar activity for the α9α10 nAChR with IC50 values of 0.79 and 0.38 nM. The latter analogue had exceptional selectivity for the α9α10 receptor subtype over other nAChR subtypes and can be considered as a drug candidate for further development. Molecular dynamics of receptor-ligand complexes allowed us to make deductions about the possible causes of increases in the affinity of key GeXIVA[1, 4] mutants for the α9α10 nAChR.
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Arginina , Ácido Aspártico , Conotoxinas , Receptores Nicotínicos , Conotoxinas/química , Conotoxinas/genética , Conotoxinas/farmacología , Receptores Nicotínicos/genética , Receptores Nicotínicos/metabolismo , Receptores Nicotínicos/química , Animales , Arginina/química , Ratas , Ácido Aspártico/química , Ácido Aspártico/genética , Antagonistas Nicotínicos/química , Antagonistas Nicotínicos/farmacología , Simulación de Dinámica Molecular , Mutagénesis , IsomerismoRESUMEN
RATIONALE: This study reports the first case of congenital hypothyroidism (CH) and alpha thalassemia in a child in China, with anemia and muscle damage as the main manifestations. Analyzing and studying this case is of great significance in reducing missed and misdiagnosed CH and will provide a clinical strategy for treating these patients. PATIENT CONCERNS: Child, female, 2 years and 7 months old, the child appeared dispirited, had poor appetite, shallow complexion, reduced activities with anemia, elevated muscle enzymes, height, and growth retardation. DIAGNOSES: The child was diagnosed with CH with alpha thalassemia. INTERVENTIONS: The patient was treated with levothyroxine sodium and anemia correction. OUTCOMES: The children's current spirit, appetite, red face, normal limb activity, physical development, and intelligence were significantly better than those of normal children of the same age. CONCLUSIONS: CH with alpha thalassemia, especially anemia and muscle damage as the main manifestations, has not been reported. Administration of levothyroxine sodium is effective in correcting anemia in patients with CH and alpha thalassemia. LESSON: Due to CH and alpha thalassemia, there are no specific symptoms and they are prone to missed diagnosis and misdiagnosis. Therefore, patients with anemia and elevated muscle enzyme levels should be routinely tested for thyroid function to diagnose them early and provide proper treatment to avoid negative consequences.
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Anemia , Hipotiroidismo Congénito , Tiroxina , Talasemia alfa , Humanos , Femenino , Talasemia alfa/complicaciones , Talasemia alfa/diagnóstico , Hipotiroidismo Congénito/complicaciones , Hipotiroidismo Congénito/diagnóstico , Hipotiroidismo Congénito/tratamiento farmacológico , Preescolar , Tiroxina/uso terapéutico , Anemia/etiología , Anemia/tratamiento farmacológico , Enfermedades Musculares/etiología , Enfermedades Musculares/diagnóstico , Enfermedades Musculares/complicacionesRESUMEN
This article proposes an adaptive fuzzy neural network (NN) command filtered impedance control for constrained robotic manipulators with disturbance observers. First, barrier Lyapunov functions are introduced to handle the full-state constraints. Second, the adaptive fuzzy NN is introduced to handle the unknown system dynamics and a disturbance observer is designed to eliminate the effect of unknown bound disturbance. Then, a modified auxiliary system is designed to suppress the input saturation effect. In addition, the command filtered technique and error compensation mechanism are used to directly obtain the derivative of the virtual control law and improve the control accuracy. The barrier Lyapunov theory is used to prove that all the signals in the closed-loop system are semiglobally uniformly ultimately bounded. Finally, simulation studies are performed to illustrate the effectiveness of the proposed control method.
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This brief is concerned with neural network (NN)-based adaptive finite-time output feedback attitude tracking control for rigid spacecraft in the presence of actuator saturation, inertial uncertainty, and external disturbance. First, a neural state observer is designed to estimate the unknown state. Then, based on the estimated state, the adaptive neural finite-time command filtered backstepping (CFB) is applied to construct virtual control signal and controller with updating law. The finite-time command filter is given to avoid the computation complexity problem in traditional backstepping, and the compensation signals based on fractional power are constructed to remove filtering errors. Using Lyapunov stability theory, we show that the attitude tracking error (TE) can converge into the desired neighborhood of the origin in finite time and all the signals in the closed-loop system are bounded in finite time although input saturation exists. The numerical simulations are used to show the effectiveness of the given algorithm.
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This article presents an event-triggered adaptive NN command-filtered control for a class of multi-input and multi-output (MIMO) nonlinear systems with unknown rate-dependent hysteresis in the actuator and the constraints on full states. The ETM is used to reduce the communication frequency between controller and actuator. The command filter technique is first employed to solve the dilemma between the nondifferentiable control signal at triggering instants and rate-dependent hysteresis input premise while avoiding the "explosion of complexity" problem. During the backstepping design, the barrier Lyapunov functions are utilized to guarantee that system states will stay in certain regions and the unknown nonlinear items are approximated by adaptive neural networks. The compensating signals are constructed to eliminate filtering errors. The estimates of unknown hysteresis parameters are updated by adaptive laws. The stability analysis is given and the effectiveness of the proposed method is verified by simulation.
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In this article, an adaptive neural-network (NN) command-filtered output-feedback control strategy is proposed for a class of stochastic nonlinear systems (SNSs) with the actuator constraint. The problem of "explosion of complexity" existing in the conventional backstepping design procedure for SNSs is successfully resolved based on the command filter technique, and the error compensation mechanism is introduced to remove effectively the influence of filtered error. By using the NNs to identify the unknown nonlinear functions, a neural-network-based state observer is designed to estimate the unmeasurable states of the SNSs. Based on the quartic Lyapunov function, the stability of stochastic closed-loop systems is analyzed. It is proved that all signals of the closed-loop systems are bounded in probability, and the tracking error approaches a small neighborhood of the origin in probability. Finally, the effectiveness of the developed control algorithm in this article is verified by a comparison example.