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Synthetic cathinones have gained increasing popularity in the illicit drug market, yet their abuse potential remains poorly understood. In this study, zebrafish were used to compare the addictive potential of three cathinone analogs, namely pentylone, eutylone, and N-ethylpentylone (NEP). The zebrafish received various doses (0 to 60 mg/kg) of the cathinone analogs by oral gavage over two sessions per day for two consecutive days to induce conditioned place preference (CPP). Pentylone, eutylone, and NEP dose-dependently induced CPP, with NEP showing significantly higher CPP than pentylone and eutylone at the dose of 20 mg/kg. The fish that received 60 mg/kg of cathinones underwent extinction, followed by reinstatement triggered by drug priming. NEP required six sessions to meet the criteria of extinction, followed by eutylone, which required four sessions, and pentylone, which required three sessions. Furthermore, NEP and eutylone at a dose of 40 mg/kg could reinstate the extinguished CPP, while 60 mg/kg of pentylone was necessary for CPP reinstatement. The persistence of susceptibility to reinstatement was also assessed at 7 and 14 days after the initial reinstatement. The CPP induced by all three cathinone analogs could be reinstated 7 days after the initial reinstatement, whereas only CPP induced by NEP, but not pentylone and eutylone, could be reinstated again after 14 days. Considering the potency to induce CPP, resistance to extinction, and the propensity for reinstatement, the abuse liability rank order of the cathinone analogs might be as follows: NEP > eutylone > pentylone. These findings suggest that the zebrafish CPP paradigm can serve as a viable model for assessing the relative abuse liability of substances.
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Alkaloids are the main medicinal components in Houttuynia cordata. In this study, two accessions 6# and 7# of H. cordata underwent thorough metabolomic analyses to identify and quantify alkaloid phytometabolites. It turned out that the alkaloid types were largely similar between 6# and 7#, and the identified 81 alkaloids could be divided into nine structural classes. However, the content of alkaloids in the two accessions was quite different. According to transcriptome data, a total of 114 differentially expressed genes related to alkaloid metabolism were screened. The alkaloid synthesis pathway of the two varieties was mainly different in the isoquinoline alkaloid biosynthesis and indole alkaloid biosynthesis; four genes A22110063c_transcript_59323, A22110063c_transcript_60118, A22110063c_transcript_51672 and A22110063c_transcript_48784 were highly expressed in 7#, which could be key candidate genes of alkaloid metabolism and warrant further analysis. These results provide a reference for the medicinal application of H. cordata and breeding alkaloid rich varieties.
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Aminoglycosides are commonly used antibiotics for treatment of gram-negative bacterial infections, however, they might act on inner ear, leading to hair-cell death and hearing loss. Currently, there is no targeted therapy for aminoglycoside ototoxicity, since the underlying mechanisms of aminoglycoside-induced hearing impairments are not fully defined. This study aimed to investigate whether the calcium channel blocker verapamil and changes in intracellular & extracellular calcium could ameliorate aminoglycoside-induced ototoxicity in zebrafish. The present findings showed that a significant decreased number of neuromasts in the lateral lines of zebrafish larvae at 5 days' post fertilization after neomycin (20 µM) and gentamicin (20 mg/mL) exposure, which was prevented by verapamil. Moreover, verapamil (10-100 µM) attenuated aminoglycoside-induced toxic response in different external calcium concentrations (33-3300 µM). The increasing extracellular calcium reduced hair cell loss from aminoglycoside exposure, while lower calcium facilitated hair cell death. In contrast, calcium channel activator Bay K8644 (20 µM) enhanced aminoglycoside-induced ototoxicity and reversed the protective action of higher external calcium on hair cell loss. However, neomycin-elicited hair cell death was not altered by caffeine, ryanodine receptor (RyR) agonist, and RyR antagonists, including thapsigargin, ryanodine, and ruthenium red. The uptake of neomycin into hair cells was attenuated by verapamil and under high external calcium concentration. Consistently, the production of reactive oxygen species (ROS) in neuromasts exposed to neomycin was also reduced by verapamil and high external calcium. Significantly, zebrafish larvae when exposed to neomycin exhibited decreased swimming distances in reaction to droplet stimulus when compared to the control group. Verapamil and elevated external calcium effectively protected the impaired swimming ability of zebrafish larvae induced by neomycin. These data imply that prevention of hair cell damage correlated with swimming behavior against aminoglycoside ototoxicity by verapamil and higher external calcium might be associated with inhibition of excessive ROS production and aminoglycoside uptake through cation channels. These findings indicate that calcium channel blocker and higher external calcium could be applied to protect aminoglycoside-induced listening impairments.
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Antibacterianos , Bloqueadores de los Canales de Calcio , Calcio , Gentamicinas , Células Ciliadas Auditivas , Neomicina , Verapamilo , Pez Cebra , Animales , Bloqueadores de los Canales de Calcio/farmacología , Calcio/metabolismo , Verapamilo/farmacología , Neomicina/toxicidad , Células Ciliadas Auditivas/efectos de los fármacos , Células Ciliadas Auditivas/metabolismo , Gentamicinas/toxicidad , Antibacterianos/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Ototoxicidad/prevención & control , Aminoglicósidos/toxicidad , Sistema de la Línea Lateral/efectos de los fármacos , Larva/efectos de los fármacos , Pérdida Auditiva/inducido químicamente , Pérdida Auditiva/prevención & controlRESUMEN
Low-cost, small-sized, and easy integrated high-performance photodetectors for photonics are still the bottleneck of photonic integrated circuits applications and have attracted increasing attention. The tunable narrow bandgap of two-dimensional (2D) layered molybdenum ditelluride (MoTe2) from â¼0.83 to â¼1.1 eV makes it one of the ideal candidates for near-infrared (NIR) photodetectors. Herein, we demonstrate an excellent waveguide-integrated NIR photodetector by transferring mechanically exfoliated 2D MoTe2onto a silicon nitride (Si3N4) waveguide. The photoconductive photodetector exhibits excellent responsivity (R), detectivity (D*), and external quantum efficiency at 1550 nm and 50 mV, which are 41.9 A W-1, 16.2 × 1010Jones, and 3360%, respectively. These optoelectronic performances are 10.2 times higher than those of the free-space device, revealing that the photoresponse of photodetectors can be enhanced due to the presence of waveguide. Moreover, the photodetector also exhibits competitive performances over a broad wavelength range from 800 to 1000 nm with a highRof 15.4 A W-1and a largeD* of 59.6 × 109Jones. Overall, these results provide an alternative and prospective strategy for high-performance on-chip broadband NIR photodetectors.
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Conditioned place preference (CPP) paradigm in zebrafish has been used to measure drug reward, but there is limited research on CPP reinstatement to determine relapse vulnerability. The present study aimed to investigate extinction and reinstatement of methamphetamine (MA)-induced CPP in zebrafish and evaluate the model's predictive validity. Zebrafish received different doses of MA (0-60 mg/kg) during CPP training. The preferred dose of MA at 40 mg/kg was used for extinction via either confined or nonconfined procedures. The extinguished CPP was reinstated by administering a priming dose of MA (20 mg/kg) or various stressors. To assess persistent susceptibility to reinstatement, MA CPP and reinstatement were retested following 14 days of abstinence. In addition, the effects of SCH23390, naltrexone, and clonidine on MA CPP during acquisition, expression, or reinstatement phases were monitored. MA induced CPP in a dose-dependent manner. Both nonconfined and confined extinction procedures time-dependently reduced the time spent on the MA-paired side. A priming dose of MA, chasing stress, or yohimbine reinstated the extinguished CPP. After 14 days of abstinence, the MA CPP remained extinguished and was significantly reinstated by MA priming or chasing stress. Similar to the observations in rodents, SCH23390 suppressed the acquisition of MA CPP, naltrexone reduced the expression and MA priming-induced reinstatement, while clonidine prevented stress-induced reinstatement of MA CPP. This work expanded the zebrafish CPP paradigm to include extinction and reinstatement phases, demonstrating predictive validity and highlighting its potential as a valuable tool for exploring drug relapse.
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Metanfetamina , Animales , Metanfetamina/farmacología , Pez Cebra , Morfina/farmacología , Extinción Psicológica , Clonidina/farmacología , Naltrexona/farmacología , RecurrenciaRESUMEN
BACKGROUND: Cortisol plays a role in the pathogenesis of central serous chorioretinopathy (CSC). CSC patients have abnormal time-dependent changes in cortisol levels. Here we report a rare case of a patient with central serous chorioretinopathy whose pigment epithelial detachment (PED) exhibited time-dependent recurrence and resolution. CASE PRESENTATION: A 47-year-old man presented in 2016 for vision loss in the left eye related to recurrent CSC. During follow-up, his PED was observed to resolve spontaneously while he was still in our clinic and recurred the next morning. Such time-dependent changes of the PED were observed in several next follow-ups without any intervention. After excluding possible external factors, the abnormal diurnal variation of cortisol was considered as the internal factor affecting PED. CONCLUSIONS: This is the first article that described the spontaneous time-dependent recurrence and resolution of PED without external interference, where endogenous cortisol may be responsible. Interventions against the abnormal cortisol level might be a potential treatment strategy for CSC. More research is urged to explore the impact of the diurnal change in cortisol levels on eyes with CSC.
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Coriorretinopatía Serosa Central , Desprendimiento de Retina , Masculino , Humanos , Persona de Mediana Edad , Coriorretinopatía Serosa Central/complicaciones , Coriorretinopatía Serosa Central/diagnóstico , Hidrocortisona , Desprendimiento de Retina/etiología , Desprendimiento de Retina/complicaciones , Epitelio Pigmentado de la Retina/patología , Tomografía de Coherencia Óptica , Angiografía con Fluoresceína , Estudios RetrospectivosRESUMEN
BACKGROUND: With the popularity of coronavirus disease 2019 (COVID-19) vaccination, some rare ocular adverse events have gradually been reported. This report shows a rare case of retinal vasculitis following COVID-19 vaccination. DESCRIPTION: A 37-year-old male complained of unilateral severe vision loss 13 days after the first dose of an inactivated COVID-19 vaccine. The initial eye examination showed gray-white edema in the macula, and scattered patchy gray-white lesions in the peripheral retina, accompanied by peripheral retinal small vessel occlusion. After glucocorticoid treatment, the gray-white lesions gradually subsided. However, due to the initial severe damage in the fundus, macular and peripheral retinal lesions were significantly atrophied, and the vision recovery was poor. CONCLUSION: The ocular adverse event in this report may be related to the inactivated COVID-19 vaccination, however, it is difficult to rule out the accidental rare adverse events after a large number of vaccinations.
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Vacunas contra la COVID-19 , COVID-19 , Vasculitis Retiniana , Adulto , Humanos , Masculino , COVID-19/complicaciones , Vacunas contra la COVID-19/efectos adversos , Angiografía con Fluoresceína , Retina/patología , Vasculitis Retiniana/diagnóstico , Vasculitis Retiniana/etiología , Vacunación/efectos adversosRESUMEN
Droplet microfluidics offers a platform from which new digital molecular assay, disease screening, wound healing and material synthesis technologies have been proposed. However, the current commercial droplet generation, assembly and imaging technologies are too expensive and rigid to permit rapid and broad-range tuning of droplet features/cargoes. This rapid prototyping bottleneck has limited further expansion of its application. Herein, an inexpensive home-made pipette droplet microfluidics kit is introduced. This kit includes elliptical pipette tips that can be fabricated with a simple DIY (Do-It-Yourself) tool, a unique tape-based or 3D printed shallow-center imaging chip that allows rapid monolayer droplet assembly/immobilization and imaging with a smart-phone camera or miniature microscope. The droplets are generated by manual or automatic pipetting without expensive and lab-bound microfluidic pumps. The droplet size and fluid viscosity/surface tension can be varied significantly because of our particular droplet generation, assembly and imaging designs. The versatility of this rapid prototyping kit is demonstrated with three representative applications that can benefit from a droplet microfluidic platform: (1) Droplets as microreactors for PCR reaction with reverse transcription to detect and quantify target RNAs. (2) Droplets as microcompartments for spirulina culturing and the optical color/turbidity changes in droplets with spirulina confirm successful photosynthetic culturing. (3) Droplets as templates/molds for controlled synthesis of gold-capped polyacrylamide/gold composite Janus microgels. The easily fabricated and user-friendly portable kit is hence ideally suited for design, training and educational labs.
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Técnicas Analíticas Microfluídicas , Microgeles , Microfluídica/métodos , Técnicas Analíticas Microfluídicas/métodos , Encapsulación Celular , Reacción en Cadena de la PolimerasaRESUMEN
Water molecules play a very important role in the hydration and dehydration process of hydrates, which may lead to distinct physical and chemical properties, affecting their availability in practical applications. However, miniaturized, integrated sensors capable of the rapid, sensitive sensing of water molecules in the hydrate are still lacking, limiting their proliferation. Here, we realize the high-sensitivity sensing of water molecules in copper sulfate pentahydrate (CuSO4·5H2O), based on an on-chip terahertz whispering gallery mode resonator (THz-WGMR) fabricated on silicon material via CMOS-compatible technologies. An integrated THz-WGMR with a high-Q factor of 3305 and a resonance frequency of 410.497 GHz was proposed and fabricated. Then, the sensor was employed to distinguish the CuSO4·xH2O (x = 5, 3, 1). The static characterization from the CuSO4·5H2O to the copper sulfate trihydrate (CuSO4·3H2O) experienced blueshifts of 0.55 GHz/µmol, whereas the dehydration process of CuSO4·3H2O to copper sulfate monohydrate (CuSO4·H2O) exhibited blueshifts of 0.21 GHz/µmol. Finally, the dynamic dehydration processes of CuSO4·5H2O to CuSO4·3H2O at different temperatures were monitored. We believe that our proposed THz-WGMR sensors with highly sensitive substance identification capabilities can provide a versatile and integrated platform for studying the transformation between substances, contributing to hydrated/crystal water-assisted biochemical applications.
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Sulfato de Cobre , Silicio , AguaRESUMEN
All-optical canonical logic unit (CLU) is the basic building block of high-speed optical logic operation and complex optical computing. By utilizing the parallelism of optical signals, multichannel multicasting of all-optical CLUs can expand the capacity of the computing system effectively. Here, we propose and experimentally demonstrate the 40 Gb/s all-optical reconfigurable two-input CLUs generated in seven wavelength channels via four-wave mixing (FWM) in the nonlinearity-enhanced silicon waveguide. By introducing reverse-biased PIN junctions to reduce nonlinear loss, the output power of converted light can be increased over 10 dB. Moreover, pumped by two optical signals and a continuous wave beam, a full set of reconfigurable CLUs is multicasted in seven parallel wavelength channels. All logic signals with error-free performance are realized. Attributing to the rate transparency of FWM and parallel multicasting of logic functions, the proposed scheme offers more flexibility and expandability in future high-speed optical logic processing and complex optical computing.
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MhOR5, an insect olfactory receptor (OR), has an occluded binding site for the odorant eugenol in both the open and closed states of the ion channel. We used atomistic molecular dynamics simulation (MD) and steered molecular dynamics to examine possible tunnels to the odorant binding site from the protein surface. Four high probability tunnels were identified in the MD results. Surprisingly, three of the tunnels connect the ligand binding site to the lipid bilayer. We found sharp 30%-50% increases or decreases in tunnel bottleneck areas over 70 nsec MD trajectories, both in the ligand-bound and unliganded OR structures. Steered MD showed that eugenol follows the tunnels to the protein surface, and the potential of mean force is quantitatively consistent with the known affinity of eugenol for MhOR5. We examined AlphaFold-generated models of 21 other insect ORs, and we found that 19 had odorant binding sites and tunnels in similar positions to MhOR5. The possibility of a tunnel between the odorant binding site and the lipid bilayer in insect ORs suggests new experiments to test molecular mechanisms for insect odorant reception.
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Receptores Odorantes , Animales , Sitios de Unión , Eugenol , Insectos/metabolismo , Ligandos , Membrana Dobles de Lípidos , Odorantes , Receptores Odorantes/químicaRESUMEN
Glucose transporter GLUT1 is ubiquitously expressed in the human body from the red cells to the blood-brain barrier to the skeletal muscles. It is physiologically relevant to understand how GLUT1 facilitates diffusion of glucose across the cell membrane. It is also pathologically relevant because GLUT1 deficiency causes neurological disorders and anemia and because GLUT1 overexpression fuels the abnormal growth of cancer cells. This article presents a quantitative investigation of GLUT1 based on all-atom molecular-dynamics (MD) simulations of the transporter embedded in lipid bilayers of asymmetric inner-and-outer-leaflet lipid compositions, subject to asymmetric intra-and-extra-cellular environments. This is in contrast with the current literature of MD studies that have not considered both of the aforementioned asymmetries of the cell membrane. The equilibrium (unbiased) dynamics of GLUT1 shows that it can facilitate glucose diffusion across the cell membrane without undergoing large-scale conformational motions. The Gibbs free-energy profile, which is still lacking in the current literature of GLUT1, quantitatively characterizes the diffusion path of glucose from the periplasm, through an extracellular gate of GLUT1, on to the binding site, and off to the cytoplasm. This transport mechanism is validated by the experimental data that GLUT1 has low water-permeability, uptake-efflux symmetry, and 10 kcal/mol Arrhenius activation barrier around 37 °C.
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Glucosa , Proteínas de Transporte de Monosacáridos , Transporte Biológico , Difusión , Glucosa/metabolismo , Transportador de Glucosa de Tipo 1/metabolismo , Humanos , Proteínas de Transporte de Monosacáridos/metabolismoRESUMEN
Dispersive time stretch has made many ultrafast applications possible owing to its high frame rate, as compared to conventional spectroscopies. By further introducing a converging time lens, this spectroscopy can resolve arbitrary emission spectra within the aperture. However, a spectral resolution of tens of picometers hinders its high-precision application. There are two limitations: the temporal aperture of the acquired signal and the actual acquisition bandwidth. To overcome these restrictions, two approaches were developed. First, a large-aperture time lens, with higher-order dispersion compensation, is used to overcome the fundamental limit of the time-bandwidth product. Second, asynchronous optical sampling, based on two frequency combs, overcomes the technical limit of the acquisition bandwidth. As a result, in this study, time-stretch spectroscopy achieved a 1-pm spectral resolution, 24-nm observation bandwidth, and 1-kHz frame rate. Moreover, it was used to observe some spectral dynamics of the random lasing process and devices with narrow spectral widths. This scheme provides essential improvement for time-stretch spectroscopy to achieve high precision.
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AQP7 is one of the four human aquaglyceroporins that facilitate glycerol transport across the cell membrane, a biophysical process that is essential in human physiology. Therefore, it is interesting to compute AQP7's affinity for its substrate (glycerol) with reasonable certainty to compare with the experimental data suggesting high affinity in contrast with most computational studies predicting low affinity. In this study aimed at computing the AQP7-glycerol affinity with high confidence, we implemented a direct computation of the affinity from unbiased equilibrium molecular dynamics (MD) simulations of three all-atom systems constituted with 0.16M, 4.32M, and 10.23M atoms, respectively. These three sets of simulations manifested a fundamental physics law that the intrinsic fluctuations of pressure in a system are inversely proportional to the system size (the number of atoms in it). These simulations showed that the computed values of glycerol-AQP7 affinity are dependent upon the system size (the inverse affinity estimations were, respectively, 47.3 mM, 1.6 mM, and 0.92 mM for the three model systems). In this, we obtained a lower bound for the AQP7-glycerol affinity (an upper bound for the dissociation constant). Namely, the AQP7-glycerol affinity is stronger than 1087/M (the dissociation constant is less than 0.92 mM). Additionally, we conducted hyper steered MD (hSMD) simulations to map out the Gibbs free-energy profile. From the free-energy profile, we produced an independent computation of the AQP7-glycerol dissociation constant being approximately 0.18 mM.
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Dopamine transporter mediates the neurotransmitter dopamine homeostasis in a sodium-dependent manner. The transport process involves an alternating access of a substrate to the extracellular and intracellular spaces, which is associated with different conformational states of the transporter. However, the underlying mechanism of modulation of the state transition remains elusive. Here we present a computational simulation study of human dopamine transporter to explore its two end states (outward-facing open and inward-facing open) that have not been determined experimentally. We show that the full-length transporter may tend to adopt the inward-facing open state in its free state. The binding of an amphetamine may not trap the transporter in the outward-facing open state with increasing length of the N-terminal. Furthermore, we identify distinct patterns in the interaction networks between the N-terminal and the intracellular region that could stabilize the state of the transporter, independent of substrate binding and phosphorylation. Our results reveal the essential role of the N-terminal dynamics in modulating the functional states of the dopamine transporter, providing molecular insights into the coupling of conformational transition and substrate passage in neurotransmitter transporters.
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Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , Simulación de Dinámica Molecular , Dopamina/metabolismo , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/química , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Humanos , Conformación Proteica , SodioRESUMEN
As an N-methyl-D-aspartate (NMDA) receptor inhibitor, ketamine has become a popular recreational substance and currently is used to address treatment-resistant depression. Since heavy ketamine use is associated with persisting psychosis, cognitive impairments, and neuronal damage, the safety of ketamine treatment for depression should be concerned. The nutrient supplement betaine has been shown to counteract the acute ketamine-induced psychotomimetic effects and cognitive dysfunction through modulating NMDA receptors. This study aimed to determine whether the adjunctive or subsequent betaine treatment would improve the enduring behavioral disturbances and hippocampal synaptic abnormality induced by repeated ketamine exposure. Mice received ketamine twice daily for 14 days, either combined with betaine co-treatment or subsequent betaine post-treatment for 7 days. Thereafter, three-chamber social approach test, reciprocal social interaction, novel location/object recognition test, forced swimming test, and head-twitch response induced by serotonergic hallucinogen were monitored. Data showed that the enduring behavioral abnormalities after repeated ketamine exposure, including disrupted social behaviors, recognition memory impairments, and increased depression-like and hallucinogen-induced head-twitch responses, were remarkably improved by betaine co-treatment or post-treatment. Consistently, betaine protected and reversed the reduced hippocampal synaptic activity, such as decreases in field excitatory post-synaptic potentiation (fEPSP), long-term potentiation (LTP), and PSD-95 levels, after repeated ketamine treatment. These results demonstrated that both co-treatment and post-treatment with betaine could effectively prevent and reverse the adverse behavioral manifestations and hippocampal synaptic plasticity after repeated ketamine use, suggesting that betaine can be used as a novel adjunct therapy with ketamine for treatment-resistant depression and provide benefits for ketamine use disorders.
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Antipsicóticos/farmacología , Conducta Animal/efectos de los fármacos , Betaína/farmacología , Hipocampo/efectos de los fármacos , Plasticidad Neuronal/efectos de los fármacos , Psicosis Inducidas por Sustancias/prevención & control , Transmisión Sináptica/efectos de los fármacos , Animales , Cognición/efectos de los fármacos , Modelos Animales de Enfermedad , Homólogo 4 de la Proteína Discs Large/metabolismo , Antagonistas de Aminoácidos Excitadores , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Femenino , Hipocampo/metabolismo , Hipocampo/fisiopatología , Ketamina , Locomoción/efectos de los fármacos , Masculino , Ratones Endogámicos ICR , Prueba de Campo Abierto/efectos de los fármacos , Psicosis Inducidas por Sustancias/etiología , Psicosis Inducidas por Sustancias/fisiopatología , Psicosis Inducidas por Sustancias/psicología , Reconocimiento en Psicología/efectos de los fármacos , Conducta Social , NataciónRESUMEN
Pyruvate metabolism requires the mitochondrial pyruvate carrier (MPC) proteins to transport pyruvate from the intermembrane space through the inner mitochondrial membrane to the mitochondrial matrix. The lack of the atomic structures of MPC hampers the understanding of the functional states of MPC and molecular interactions with the substrate or inhibitor. Here, we develop the de novo models of human MPC complexes and characterize the conformational dynamics of the MPC heterodimer formed by MPC1 and MPC2 (MPC1/2) by computational simulations. Our results reveal that functional MPC1/2 prefers to adopt an inward-open conformation, with the carrier open to the matrix side, whereas the outward-open states are less populated. The energy barrier for pyruvate transport in MPC1/2 is low enough, and the inhibitor UK5099 blocks the pyruvate transport by stably binding to MPC1/2. Notably, consistent with experimental results, the MPC1 L79H mutation significantly alters the conformations of MPC1/2 and thus fails for substrate transport. However, the MPC1 R97W mutation seems to retain the transport activity. The present de novo models of MPC complexes provide structural insights into the conformational states of MPC complexes and mechanistic understanding of interactions between the substrate/inhibitor and MPC proteins.
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Proteínas de Transporte de Membrana Mitocondrial/química , Transportadores de Ácidos Monocarboxílicos , Humanos , Mitocondrias , Proteínas de Transporte de Membrana Mitocondrial/metabolismo , Membranas Mitocondriales/metabolismo , Proteínas Mitocondriales/metabolismo , Ácido PirúvicoRESUMEN
Terahertz isolators, one of the typical nonreciprocal devices that can break Lorentz reciprocity, are indispensable building blocks in terahertz systems for their critical functionality of manipulating the terahertz flow. Here, we report an integrated terahertz isolator based on the magneto-optical effect of a nonreciprocal resonator. By optimizing the magneto-optical property and the loss of the resonator, we experimentally observe unidirectional propagation with an ultrahigh isolation ratio reaching up to 52 dB and an insertion loss around 7.5 dB at ~0.47 THz. With a thermal tuning method and periodic resonances, the isolator can operate at different central frequencies in the range of 0.405-0.495 THz. This on-chip terahertz isolator will not only inspire more solutions for integrated terahertz nonreciprocal devices, but also have the feasibility for practical applications such as terahertz sensing and reducing unnecessary reflections in terahertz systems.
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Rapid point-of-care (POC) quantification of low virus RNA load would significantly reduce the turn-around time for the PCR test and help contain a fast-spreading epidemic. Herein, we report a droplet digital PCR (ddPCR) platform that can achieve this sensitivity and rapidity without bulky lab-bound equipment. The key technology is a flattened pipette tip with an elliptical cross-section, which extends a high aspect-ratio microfluidic chip design to pipette scale, for rapid (<5 min) generation of several thousand monodispersed droplets â¼150 to 350 µm in size with a CV of â¼2.3%. A block copolymer surfactant (polyoxyalkylene F127) is used to stabilize these large droplets in oil during thermal cycling. At this droplet size and number, positive droplets can be counted by eye or imaged by a smartphone with appropriate illumination/filtering to accurately quantify up to 100 target copies. We demonstrate with 2019 nCoV-PCR assay LODs of 3.8 copies per 20 µL of sample and a dynamic range of 4-100 copies. The ddPCR platform is shown to be inhibitor resistant with spiked saliva samples, suggesting RNA extraction may not be necessary. It represents a rapid 1.5-h POC quantitative PCR test that requires just a pipette equipped with elliptical pipette tip, a commercial portable thermal cycler, a smartphone, and a portable trans-illuminator, without bulky and expensive micropumps and optical detectors that prevent POC application.