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1.
Cell ; 181(1): 115-135, 2020 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-32220309

RESUMO

Techniques for neuromodulation serve as effective routes to care of patients with many types of challenging conditions. Continued progress in this field of medicine will require (1) improvements in our understanding of the mechanisms of neural control over organ function and (2) advances in technologies for precisely modulating these functions in a programmable manner. This review presents recent research on devices that are relevant to both of these goals, with an emphasis on multimodal operation, miniaturized dimensions, biocompatible designs, advanced neural interface schemes, and battery-free, wireless capabilities. A future that involves recording and modulating neural activity with such systems, including those that exploit closed-loop strategies and/or bioresorbable designs, seems increasingly within reach.


Assuntos
Materiais Biocompatíveis/uso terapêutico , Sistema Nervoso , Próteses e Implantes , Animais , Humanos , Estimulação Elétrica Nervosa Transcutânea/métodos
2.
Nature ; 597(7877): 503-510, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34552257

RESUMO

Large, distributed collections of miniaturized, wireless electronic devices1,2 may form the basis of future systems for environmental monitoring3, population surveillance4, disease management5 and other applications that demand coverage over expansive spatial scales. Aerial schemes to distribute the components for such networks are required, and-inspired by wind-dispersed seeds6-we examined passive structures designed for controlled, unpowered flight across natural environments or city settings. Techniques in mechanically guided assembly of three-dimensional (3D) mesostructures7-9 provide access to miniature, 3D fliers optimized for such purposes, in processes that align with the most sophisticated production techniques for electronic, optoelectronic, microfluidic and microelectromechanical technologies. Here we demonstrate a range of 3D macro-, meso- and microscale fliers produced in this manner, including those that incorporate active electronic and colorimetric payloads. Analytical, computational and experimental studies of the aerodynamics of high-performance structures of this type establish a set of fundamental considerations in bio-inspired design, with a focus on 3D fliers that exhibit controlled rotational kinematics and low terminal velocities. An approach that represents these complex 3D structures as discrete numbers of blades captures the essential physics in simple, analytical scaling forms, validated by computational and experimental results. Battery-free, wireless devices and colorimetric sensors for environmental measurements provide simple examples of a wide spectrum of applications of these unusual concepts.


Assuntos
Biomimética , Equipamentos e Provisões Elétricas , Miniaturização/instrumentação , Sementes , Vento , Tecnologia sem Fio/instrumentação , Colorimetria , Monitoramento Ambiental/instrumentação , Monitoramento Ambiental/métodos , Fenômenos Mecânicos , Microfluídica , Vigilância da População/métodos , Rotação
3.
Proc Natl Acad Sci U S A ; 121(7): e2315476121, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38319970

RESUMO

Marine photosynthetic dinoflagellates are a group of successful phytoplankton that can form red tides in the ocean and also symbiosis with corals. These features are closely related to the photosynthetic properties of dinoflagellates. We report here three structures of photosystem I (PSI)-chlorophylls (Chls) a/c-peridinin protein complex (PSI-AcpPCI) from two species of dinoflagellates by single-particle cryoelectron microscopy. The crucial PsaA/B subunits of a red tidal dinoflagellate Amphidinium carterae are remarkably smaller and hence losing over 20 pigment-binding sites, whereas its PsaD/F/I/J/L/M/R subunits are larger and coordinate some additional pigment sites compared to other eukaryotic photosynthetic organisms, which may compensate for the smaller PsaA/B subunits. Similar modifications are observed in a coral symbiotic dinoflagellate Symbiodinium species, where two additional core proteins and fewer AcpPCIs are identified in the PSI-AcpPCI supercomplex. The antenna proteins AcpPCIs in dinoflagellates developed some loops and pigment sites as a result to accommodate the changed PSI core, therefore the structures of PSI-AcpPCI supercomplex of dinoflagellates reveal an unusual protein assembly pattern. A huge pigment network comprising Chls a and c and various carotenoids is revealed from the structural analysis, which provides the basis for our deeper understanding of the energy transfer and dissipation within the PSI-AcpPCI supercomplex, as well as the evolution of photosynthetic organisms.


Assuntos
Antozoários , Dinoflagellida , Animais , Antozoários/metabolismo , Complexos de Proteínas Captadores de Luz/metabolismo , Dinoflagellida/metabolismo , Proliferação Nociva de Algas , Simbiose , Microscopia Crioeletrônica , Complexo de Proteína do Fotossistema I/metabolismo , Clorofila/metabolismo
4.
Proc Natl Acad Sci U S A ; 121(22): e2404007121, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38768347

RESUMO

Sensations of heat and touch produced by receptors in the skin are of essential importance for perceptions of the physical environment, with a particularly powerful role in interpersonal interactions. Advances in technologies for replicating these sensations in a programmable manner have the potential not only to enhance virtual/augmented reality environments but they also hold promise in medical applications for individuals with amputations or impaired sensory function. Engineering challenges are in achieving interfaces with precise spatial resolution, power-efficient operation, wide dynamic range, and fast temporal responses in both thermal and in physical modulation, with forms that can extend over large regions of the body. This paper introduces a wireless, skin-compatible interface for thermo-haptic modulation designed to address some of these challenges, with the ability to deliver programmable patterns of enhanced vibrational displacement and high-speed thermal stimulation. Experimental and computational investigations quantify the thermal and mechanical efficiency of a vertically stacked design layout in the thermo-haptic stimulators that also supports real-time, closed-loop control mechanisms. The platform is effective in conveying thermal and physical information through the skin, as demonstrated in the control of robotic prosthetics and in interactions with pressure/temperature-sensitive touch displays.


Assuntos
Tato , Realidade Virtual , Tecnologia sem Fio , Humanos , Tecnologia sem Fio/instrumentação , Tato/fisiologia , Pele , Robótica/instrumentação , Robótica/métodos
5.
Proc Natl Acad Sci U S A ; 121(14): e2400868121, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38547066

RESUMO

Partial cystectomy procedures for urinary bladder-related dysfunction involve long recovery periods, during which urodynamic studies (UDS) intermittently assess lower urinary tract function. However, UDS are not patient-friendly, they exhibit user-to-user variability, and they amount to snapshots in time, limiting the ability to collect continuous, longitudinal data. These procedures also pose the risk of catheter-associated urinary tract infections, which can progress to ascending pyelonephritis due to prolonged lower tract manipulation in high-risk patients. Here, we introduce a fully bladder-implantable platform that allows for continuous, real-time measurements of changes in mechanical strain associated with bladder filling and emptying via wireless telemetry, including a wireless bioresorbable strain gauge validated in a benchtop partial cystectomy model. We demonstrate that this system can reproducibly measure real-time changes in a rodent model up to 30 d postimplantation with minimal foreign body response. Studies in a nonhuman primate partial cystectomy model demonstrate concordance of pressure measurements up to 8 wk compared with traditional UDS. These results suggest that our system can be used as a suitable alternative to UDS for long-term postoperative bladder recovery monitoring.


Assuntos
Bexiga Urinária , Infecções Urinárias , Animais , Humanos , Bexiga Urinária/cirurgia , Urodinâmica/fisiologia , Próteses e Implantes , Cistectomia
6.
N Engl J Med ; 388(18): 1668-1679, 2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-36876735

RESUMO

BACKGROUND: Data regarding clinical outcomes after intravascular imaging-guided percutaneous coronary intervention (PCI) for complex coronary-artery lesions, as compared with outcomes after angiography-guided PCI, are limited. METHODS: In this prospective, multicenter, open-label trial in South Korea, we randomly assigned patients with complex coronary-artery lesions in a 2:1 ratio to undergo either intravascular imaging-guided PCI or angiography-guided PCI. In the intravascular imaging group, the choice between intravascular ultrasonography and optical coherence tomography was at the operators' discretion. The primary end point was a composite of death from cardiac causes, target-vessel-related myocardial infarction, or clinically driven target-vessel revascularization. Safety was also assessed. RESULTS: A total of 1639 patients underwent randomization, with 1092 assigned to undergo intravascular imaging-guided PCI and 547 assigned to undergo angiography-guided PCI. At a median follow-up of 2.1 years (interquartile range, 1.4 to 3.0), a primary end-point event had occurred in 76 patients (cumulative incidence, 7.7%) in the intravascular imaging group and in 60 patients (cumulative incidence, 12.3%) in the angiography group (hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.89; P = 0.008). Death from cardiac causes occurred in 16 patients (cumulative incidence, 1.7%) in the intravascular imaging group and in 17 patients (cumulative incidence, 3.8%) in the angiography group; target-vessel-related myocardial infarction occurred in 38 (cumulative incidence, 3.7%) and 30 (cumulative incidence, 5.6%), respectively; and clinically driven target-vessel revascularization in 32 (cumulative incidence, 3.4%) and 25 (cumulative incidence, 5.5%), respectively. There were no apparent between-group differences in the incidence of procedure-related safety events. CONCLUSIONS: Among patients with complex coronary-artery lesions, intravascular imaging-guided PCI led to a lower risk of a composite of death from cardiac causes, target-vessel-related myocardial infarction, or clinically driven target-vessel revascularization than angiography-guided PCI. (Supported by Abbott Vascular and Boston Scientific; RENOVATE-COMPLEX-PCI ClinicalTrials.gov number, NCT03381872).


Assuntos
Doença da Artéria Coronariana , Stents Farmacológicos , Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , Angiografia Coronária/efeitos adversos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Doença da Artéria Coronariana/etiologia , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Estudos Prospectivos , Resultado do Tratamento , Ultrassonografia de Intervenção/métodos
7.
J Neurosci ; 44(15)2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38471780

RESUMO

Following peripheral nerve injury, denervated tissues can be reinnervated via regeneration of injured neurons or collateral sprouting of neighboring uninjured afferents into denervated territory. While there has been substantial focus on mechanisms underlying regeneration, collateral sprouting has received less attention. Here, we used immunohistochemistry and genetic neuronal labeling to define the subtype specificity of sprouting-mediated reinnervation of plantar hindpaw skin in the mouse spared nerve injury (SNI) model, in which productive regeneration cannot occur. Following initial loss of cutaneous afferents in the tibial nerve territory, we observed progressive centripetal reinnervation by multiple subtypes of neighboring uninjured fibers into denervated glabrous and hairy plantar skin of male mice. In addition to dermal reinnervation, CGRP-expressing peptidergic fibers slowly but continuously repopulated denervated epidermis, Interestingly, GFRα2-expressing nonpeptidergic fibers exhibited a transient burst of epidermal reinnervation, followed by a trend towards regression. Presumptive sympathetic nerve fibers also sprouted into denervated territory, as did a population of myelinated TrkC lineage fibers, though the latter did so inefficiently. Conversely, rapidly adapting Aß fiber and C fiber low threshold mechanoreceptor (LTMR) subtypes failed to exhibit convincing sprouting up to 8 weeks after nerve injury in males or females. Optogenetics and behavioral assays in male mice further demonstrated the functionality of collaterally sprouted fibers in hairy plantar skin with restoration of punctate mechanosensation without hypersensitivity. Our findings advance understanding of differential collateral sprouting among sensory neuron subpopulations and may guide strategies to promote the progression of sensory recovery or limit maladaptive sensory phenomena after peripheral nerve injury.


Assuntos
Traumatismos dos Nervos Periféricos , Feminino , Camundongos , Masculino , Animais , Regeneração Nervosa/fisiologia , Pele/inervação , Neurogênese , Neurônios Aferentes/fisiologia
8.
J Neurosci ; 44(30)2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38777598

RESUMO

Magnetogenetics was developed to remotely control genetically targeted neurons. A variant of magnetogenetics uses magnetic fields to activate transient receptor potential vanilloid (TRPV) channels when coupled with ferritin. Stimulation with static or RF magnetic fields of neurons expressing these channels induces Ca2+ transients and modulates behavior. However, the validity of ferritin-based magnetogenetics has been questioned due to controversies surrounding the underlying mechanisms and deficits in reproducibility. Here, we validated the magnetogenetic approach Ferritin-iron Redistribution to Ion Channels (FeRIC) using electrophysiological (Ephys) and imaging techniques. Previously, interference from RF stimulation rendered patch-clamp recordings inaccessible for magnetogenetics. We solved this limitation for FeRIC, and we studied the bioelectrical properties of neurons expressing TRPV4 (nonselective cation channel) and transmembrane member 16A (TMEM16A; chloride-permeable channel) coupled to ferritin (FeRIC channels) under RF stimulation. We used cultured neurons obtained from the rat hippocampus of either sex. We show that RF decreases the membrane resistance (Rm) and depolarizes the membrane potential in neurons expressing TRPV4FeRIC RF does not directly trigger action potential firing but increases the neuronal basal spiking frequency. In neurons expressing TMEM16AFeRIC, RF decreases the Rm, hyperpolarizes the membrane potential, and decreases the spiking frequency. Additionally, we corroborated the previously described biochemical mechanism responsible for RF-induced activation of ferritin-coupled ion channels. We solved an enduring problem for ferritin-based magnetogenetics, obtaining direct Ephys evidence of RF-induced activation of ferritin-coupled ion channels. We found that RF does not yield instantaneous changes in neuronal membrane potentials. Instead, RF produces responses that are long-lasting and moderate, but effective in controlling the bioelectrical properties of neurons.


Assuntos
Ferritinas , Neurônios , Animais , Ferritinas/metabolismo , Ratos , Neurônios/fisiologia , Masculino , Feminino , Canais de Cátion TRPV/metabolismo , Canais de Cátion TRPV/genética , Células Cultivadas , Campos Magnéticos , Ratos Sprague-Dawley , Potenciais da Membrana/fisiologia , Técnicas de Patch-Clamp , Hipocampo/fisiologia , Hipocampo/citologia
9.
Lancet ; 404(10457): 1029-1039, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39236729

RESUMO

BACKGROUND: Despite the detailed imaging information provided by optical coherence tomography (OCT) during percutaneous coronary intervention (PCI), clinical benefits of this imaging technique in this setting remain uncertain. The aim of the OCCUPI trial was to compare the clinical benefits of OCT-guided versus angiography-guided PCI for complex lesions, assessed as the rate of major adverse cardiac events at 1 year. METHODS: This investigator-initiated, multicentre, randomised, open-label, superiority trial conducted at 20 hospitals in South Korea enrolled patients aged 19-85 years for whom PCI with drug-eluting stents was clinically indicated. After diagnostic angiography, clinical and angiographic findings were assessed to identify patients who met the criterion of having one or more complex lesions. Patients were randomly assigned 1:1 to receive PCI with OCT guidance (OCT-guidance group) or angiography guidance without OCT (angiography-guidance group). Web-response permuted-block randomisation (mixed blocks of four or six) was used at each participating site to allocate patients. The allocation sequence was computer-generated by an external programmer who was not involved in the rest of the trial. Outcome assessors were masked to group assignment. Patients, follow-up health-care providers, and data analysers were not masked. PCI was done according to conventional standard methods with everolimus-eluting stents. The primary endpoint was major adverse cardiac events (a composite of cardiac death, myocardial infarction, stent thrombosis, or ischaemia-driven target-vessel revascularisation), 1 year after PCI. The primary analysis was done in the intention-to-treat population. The margin used to establish superiority was 1·0 as a hazard ratio. This trial is registered with ClinicalTrials.gov (NCT03625908) and is completed. FINDINGS: Between Jan 9, 2019, and Sept 22, 2022, 1604 patients requiring PCI with drug-eluting stents for complex lesions were randomly assigned to receive either OCT-guided PCI (n=803) or angiography-guided PCI (n=801). 1290 (80%) of 1604 patients were male and 314 (20%) were female. The median age of patients at randomisation was 64 years (IQR 57-70). 1588 (99%) patients completed 1-year follow-up. The primary endpoint occurred in 37 (5%) of 803 patients in the OCT-guided PCI group and 59 (7%) of 801 patients in the angiography-guided PCI group (absolute difference -2·8% [95% CI -5·1 to -0·4]; hazard ratio 0·62 [95% CI 0·41 to 0·93]; p=0·023). Rates of stroke, bleeding events, and contrast-induced nephropathy were not significantly different across the two groups. INTERPRETATION: Among patients who required drug-eluting stent implantation for complex lesions, OCT guidance resulted in a lower incidence of major adverse cardiac events at 1 year compared with angiography guidance. These findings indicate the existence of a therapeutic benefit of OCT as an intravascular imaging technique for PCI guidance in patients with complex coronary lesions. FUNDING: Abbott Vascular and Cardiovascular Research Center. TRANSLATION: For the Korean translation of the abstract see Supplementary Materials section.


Assuntos
Angiografia Coronária , Stents Farmacológicos , Intervenção Coronária Percutânea , Tomografia de Coerência Óptica , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/terapia , Intervenção Coronária Percutânea/métodos , República da Coreia , Tomografia de Coerência Óptica/métodos , Resultado do Tratamento
10.
Brief Bioinform ; 24(6)2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37798251

RESUMO

Natural products have successfully treated several diseases using a multi-component, multi-target mechanism. However, a precise mechanism of action (MOA) has not been identified. Systems pharmacology methods have been used to overcome these challenges. However, there is a limitation as those similar mechanisms of similar components cannot be identified. In this study, comparisons of physicochemical descriptors, molecular docking analysis and RNA-seq analysis were performed to compare the MOA of similar compounds and to confirm the changes observed when similar compounds were mixed and used. Various analyses have confirmed that compounds with similar structures share similar MOA. We propose an advanced method for in silico experiments in herbal medicine research based on the results. Our study has three novel findings. First, an advanced network pharmacology research method was suggested by partially presenting a solution to the difficulty in identifying multi-component mechanisms. Second, a new natural product analysis method was proposed using large-scale molecular docking analysis. Finally, various biological data and analysis methods were used, such as in silico system pharmacology, docking analysis and drug response RNA-seq. The results of this study are meaningful in that they suggest an analysis strategy that can improve existing systems pharmacology research analysis methods by showing that natural product-derived compounds with the same scaffold have the same mechanism.


Assuntos
Produtos Biológicos , Medicamentos de Ervas Chinesas , Plantas Medicinais , Simulação de Acoplamento Molecular , Transcriptoma , Produtos Biológicos/farmacologia , Extratos Vegetais , Medicina Tradicional Chinesa
11.
Brain ; 147(9): 2983-2990, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-38916065

RESUMO

Somatic mosaicism in a fraction of brain cells causes neurodevelopmental disorders, including childhood intractable epilepsy. However, the threshold for somatic mosaicism leading to brain dysfunction is unknown. In this study, we induced various mosaic burdens in focal cortical dysplasia type II (FCD II) mice, featuring mTOR somatic mosaicism and spontaneous behavioural seizures. The mosaic burdens ranged from approximately 1000 to 40 000 neurons expressing the mTOR mutant in the somatosensory or medial prefrontal cortex. Surprisingly, approximately 8000-9000 neurons expressing the MTOR mutant, extrapolated to constitute 0.08%-0.09% of total cells or roughly 0.04% of variant allele frequency in the mouse hemicortex, were sufficient to trigger epileptic seizures. The mutational burden was correlated with seizure frequency and onset, with a higher tendency for electrographic inter-ictal spikes and beta- and gamma-frequency oscillations in FCD II mice exceeding the threshold. Moreover, mutation-negative FCD II patients in deep sequencing of their bulky brain tissues revealed somatic mosaicism of the mTOR pathway genes as low as 0.07% in resected brain tissues through ultra-deep targeted sequencing (up to 20 million reads). Thus, our study suggests that extremely low levels of somatic mosaicism can contribute to brain dysfunction.


Assuntos
Epilepsias Parciais , Mosaicismo , Serina-Treonina Quinases TOR , Animais , Camundongos , Humanos , Epilepsias Parciais/genética , Epilepsias Parciais/fisiopatologia , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Masculino , Feminino , Malformações do Desenvolvimento Cortical do Grupo II/genética , Malformações do Desenvolvimento Cortical do Grupo II/fisiopatologia , Encéfalo/fisiopatologia , Encéfalo/metabolismo , Mutação , Criança , Neurônios/metabolismo , Camundongos Transgênicos , Eletroencefalografia , Modelos Animais de Doenças , Epilepsia , Malformações do Desenvolvimento Cortical do Grupo I
12.
Nature ; 565(7739): 361-365, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30602791

RESUMO

The fast-growing field of bioelectronic medicine aims to develop engineered systems that can relieve clinical conditions by stimulating the peripheral nervous system1-5. This type of technology relies largely on electrical stimulation to provide neuromodulation of organ function or pain. One example is sacral nerve stimulation to treat overactive bladder, urinary incontinence and interstitial cystitis (also known as bladder pain syndrome)4,6,7. Conventional, continuous stimulation protocols, however, can cause discomfort and pain, particularly when treating symptoms that can be intermittent (for example, sudden urinary urgency)8. Direct physical coupling of electrodes to the nerve can lead to injury and inflammation9-11. Furthermore, typical therapeutic stimulators target large nerve bundles that innervate multiple structures, resulting in a lack of organ specificity. Here we introduce a miniaturized bio-optoelectronic implant that avoids these limitations by using (1) an optical stimulation interface that exploits microscale inorganic light-emitting diodes to activate opsins; (2) a soft, high-precision biophysical sensor system that allows continuous measurements of organ function; and (3) a control module and data analytics approach that enables coordinated, closed-loop operation of the system to eliminate pathological behaviours as they occur in real-time. In the example reported here, a soft strain gauge yields real-time information on bladder function in a rat model. Data algorithms identify pathological behaviour, and automated, closed-loop optogenetic neuromodulation of bladder sensory afferents normalizes bladder function. This all-optical scheme for neuromodulation offers chronic stability and the potential to stimulate specific cell types.


Assuntos
Neurônios/fisiologia , Optogenética/instrumentação , Optogenética/métodos , Bexiga Urinária/inervação , Bexiga Urinária/fisiologia , Tecnologia sem Fio/instrumentação , Algoritmos , Animais , Células Cultivadas , Eletrônica , Feminino , Gânglios Espinais/citologia , Humanos , Neurônios/citologia , Ratos , Ratos Sprague-Dawley , Raízes Nervosas Espinhais/citologia
13.
Nano Lett ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847791

RESUMO

This work reports in situ (active) electrochemical control over the coupling strength between semiconducting nanoplatelets and a plasmonic cavity. We found that by applying a reductive bias to an Al nanoparticle lattice working electrode the number of CdSe nanoplatelet emitters that can couple to the cavity is decreased. Strong coupling can be reversibly recovered by discharging the lattice at oxidative potentials relative to the conduction band edge reduction potential of the emitters. By correlating the number of electrons added or removed with the measured coupling strength, we identified that loss and recovery of strong coupling are likely hindered by side processes that trap and/or inhibit electrons from populating the nanoplatelet conduction band. These findings demonstrate tunable, external control of strong coupling and offer prospects to tune selectivity in chemical reactions.

14.
BMC Plant Biol ; 24(1): 353, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693493

RESUMO

BACKGROUND: Wasabi, a Brassicaceae member, is well-known for its unique pungent and hot flavor which is produced from glucosinolate (GSL) degradation. Myrosinase (MYR) is a principle enzyme catalyzing the primary conversion of GSLs to GSL hydrolysis products (GHPs) which is responsible for plant defense system and food quality. Due to the limited information in relation to MYRs present in wasabi (Wasabia japonica M.), this study aimed to identify the MYR isogenes in W. japonica and analyze their roles in relation to GSL metabolism. RESULTS: In results, WjMYRI-1 was abundantly expressed in all organs, whereas WjMYRI-2 showed only trace expression levels. WjMYRII was highly expressed in the aboveground tissues. Interestingly, WjMYRII expression was significantly upregulated by certain abiotic factors, such as methyl jasmonate (more than 40-fold in petioles and 15-fold in leaves) and salt (tenfold in leaves). Young leaves and roots contained 97.89 and 91.17 µmol‧g-1 of GSL, whereas less GSL was produced in mature leaves and petioles (38.36 and 44.79 µmol‧g-1, respectively). Similar pattern was observed in the accumulation of GHPs in various plant organs. Notably, despite the non-significant changes in GSL production, abiotic factors treated samples enhanced significantly GHP content. Pearson's correlation analysis revealed that WjMYRI-1 expression significantly correlated with GSL accumulation and GHP formation, suggesting the primary role of WjMYRI-1-encoding putative protein in GSL degradation. In contrast, WjMYRII expression level showed no correlation with GSL or GHP content, suggesting another physiological role of WjMYRII in stress-induced response. CONCLUSIONS: In conclusions, three potential isogenes (WjMYRI-1, WjMYRI-2, and WjMYRII) encoding for different MYR isoforms in W. japonica were identified. Our results provided new insights related to MYR and GSL metabolism which are important for the implications of wasabi in agriculture, food and pharmaceutical industry. Particularly, WjMYRI-1 may be primarily responsible for GSL degradation, whereas WjMYRII (clade II) may be involved in other regulatory pathways induced by abiotic factors.


Assuntos
Acetatos , Glucosinolatos , Glicosídeo Hidrolases , Glucosinolatos/metabolismo , Glicosídeo Hidrolases/metabolismo , Glicosídeo Hidrolases/genética , Regulação da Expressão Gênica de Plantas , Brassicaceae/genética , Brassicaceae/metabolismo , Brassicaceae/enzimologia , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Folhas de Planta/metabolismo , Folhas de Planta/genética
15.
J Neuroinflammation ; 21(1): 180, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39044290

RESUMO

This study investigated the role of O-GlcNAc cycling in Alzheimer's disease-related changes in brain pathophysiology induced by chronic REM sleep deprivation (CSD) in mice. CSD increased amyloid beta (Aß) and p-Tau accumulation and impaired learning and memory (L/M) function. CSD decreased dendritic length and spine density. CSD also increased the intensity of postsynaptic density protein-95 (PSD-95) staining. All of these Alzheimer's disease (AD) pathogenic changes were effectively reversed through glucosamine (GlcN) treatment by enhancing O-GlcNAcylation. Interestingly, the lelvel of O-GlcNAcylated-Tau (O-Tau) exhibited an opposite trend compared to p-Tau, as it was elevated by CSD and suppressed by GlcN treatment. CSD increased neuroinflammation, as indicated by elevated levels of glial fibrillary acidic protein and IBA-1-positive glial cells in the brain, which were suppressed by GlcN treatment. CSD promoted the phosphorylation of GSK3ß and led to an upregulation in the expression of endoplasmic reticulum (ER) stress regulatory proteins and genes. These alterations were effectively suppressed by GlcN treatment. Minocycline not only suppressed neuroinflammation induced by CSD, but it also rescued the decrease in O-GlcNAc levels caused by CSD. Minocycline also reduced AD neuropathy without affecting CSD-induced ER stress. Notably, overexpressing O-GlcNAc transferase in the dentate gyrus region of the mouse brain rescued CSD-induced cognitive dysfunction, neuropathy, neuroinflammation, and ER stress responses. Collectively, our findings reveal that dysregulation of O-GlcNAc cycling underlies CSD-induced AD pathology and demonstrate that restoration of OGlcNAcylation protects against CSD-induced neurodegeneration.


Assuntos
Doença de Alzheimer , Encéfalo , Privação do Sono , Animais , Camundongos , Privação do Sono/metabolismo , Privação do Sono/complicações , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Encéfalo/metabolismo , Encéfalo/patologia , Masculino , Camundongos Endogâmicos C57BL , Proteínas tau/metabolismo , Acetilglucosamina/metabolismo , N-Acetilglucosaminiltransferases/metabolismo , Sono REM/fisiologia , Peptídeos beta-Amiloides/metabolismo
16.
J Intern Med ; 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39073177

RESUMO

BACKGROUND: Cardiopulmonary resuscitation (CPR) is the cornerstone intervention for cardiac arrest, with extracorporeal CPR (ECPR) demonstrating enhanced survival and neurologic outcomes in in-hospital cardiac arrest. This study explores the time interval between CPR initiation and the onset of extracorporeal membrane oxygenation (ECMO) in ECPR recipients, investigating its impact on survival outcomes. METHODS: This retrospective analysis included 1950 adults who received CPR at a single medical center between March 2019 and April 2023. Data from 198 adult patients who had ECMO inserted during CPR were analyzed. The interval from CPR initiation to ECMO initiation was quantified and categorized as ≤20, 20-40, and >40 min. Cox regression analysis assessed associations between CPR-to-ECMO time and short- and long-term mortalities. RESULTS: Among the 198 patients who underwent ECPR, 116 (58.6%) experienced 30-day mortality. Initiation of ECMO within 20 min occurred in 46 (23.2%), whereas 74 (37.4%) had ECMO initiated after 40 min. Cox regression revealed a significant association between time from CPR to ECMO initiation and 30-day mortality (adjusted hazard ratio [HR]: 2.20 in >40 min, HR: 2.63 in 20-40 min, p = 0.006) and 6-month mortality (HR: 1.81, in >40 min, HR: 1.99 in 20-40 min, p = 0.021). CONCLUSIONS: This study revealed that, in ECPR recipients, a shorter duration between CPR initiation and ECMO flow commencement is associated with improved short- and long-term patient prognoses. These findings emphasize the critical role of timely ECMO application in optimizing outcomes for patients undergoing ECPR.

17.
Small ; 20(34): e2400484, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38564789

RESUMO

Developing a robust artificial intelligence of things (AIoT) system with a self-powered triboelectric sensor for harsh environment is challenging because environmental fluctuations are reflected in triboelectric signals. This study presents an environmentally robust triboelectric tire monitoring system with deep learning to capture driving information in the triboelectric signals generated from tire-road friction. The optimization of the process and structure of a laser-induced graphene (LIG) electrode layer in the triboelectric tire is conducted, enabling the tire to detect universal driving information for vehicles/robotic mobility, including rotation speeds of 200-2000 rpm and contact fractions of line. Employing a hybrid model combining short-term Fourier transform with a convolution neural network-long short-term memory, the LIG-based triboelectric tire monitoring (LTTM) system decouples the driving information, such as traffic lines and road states, from varied environmental conditions of humidity (10%-90%) and temperatures (50-70 °C). The real-time line and road state recognition of the LTTM system is confirmed on a mobile platform across diverse environmental conditions, including fog, dampness, intense sunlight, and heat shimmer. This work provides an environmentally robust monitoring AIoT system by introducing a self-powered triboelectric sensor and hybrid deep learning for smart mobility.

18.
Small ; 20(9): e2305796, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37857585

RESUMO

Although various types of bifacial solar cells exist, few studies have been conducted on bifacial semitransparent CuInSe2 solar cells (BS-CISe SCs) despite the attractive potential in power generation from both sides in an albedo environment. The optimized BS-CISe SCs with 300 and 800 nm-thick absorber via a streamlined single-stage co-evaporation process exhibit a power conversion efficiency (PCE) of 6.32% and 10.6%, respectively. When double-sided total 2.0 sun illumination is assumed in an albedo environment, the bifacial power generation densities (BPGD) of them increases to 9.41% and 13.9%. Four-terminal bifacial semitransparent tandem solar cells (4T-BST SCs) are fabricated to increase the BPGD by mechanically stacking a BS-perovskite (PVK) top cell on top of a BS-CISe bottom cell with the 300 and 800 nm-thick absorber layers. When summed up, the best top and bottom cell PCEs of the 4T-BST SC with 300 and 800 nm-thick BS-CISe SC are 18.8% and 21.1%, respectively. However, the practical BPGD values of the 4T-BST SC under total 2 sun illumination are interestingly 23.4% and 24.4%, respectively. This is because the BS-CISe bottom cell's thickness affects how much rear-side illumination is transmitted to the BS-PVK top cell, increasing its current density and BPGD.

19.
Small ; : e2403147, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38989706

RESUMO

All-solid-state batteries (ASSBs) possess the advantage of ensuring safety while simultaneously maximizing energy density, making them suitable for next-generation battery models. In particular, sulfide solid electrolytes (SSEs) are viewed as promising candidates for ASSB electrolytes due to their excellent ionic conductivity. However, a limitation exists in the form of interfacial side reactions occurring between the SSEs and cathode active materials (CAMs), as well as the generation of sulfide-based gases within the SSE. These issues lead to a reduction in the capacity of CAMs and an increase in internal resistance within the cell. To address these challenges, cathode composite materials incorporating zinc oxide (ZnO) are fabricated, effectively reducing various side reactions occurring in CAMs. Acting as a semiconductor, ZnO helps mitigate the rapid oxidation of the solid electrolyte facilitated by an electronic pathway, thereby minimizing side reactions, while maintaining electron pathways to the active material. Additionally, it absorbs sulfide-based gases, thus protecting the lithium ions within CAMs. In this study, the mass spectrometer is employed to observe gas generation phenomena within the ASSB cell. Furthermore, a clear elucidation of the side reactions occurring at the cathode and the causes of capacity reduction in ASSB are provided through density functional theory calculations.

20.
Bioinformatics ; 39(1)2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36688702

RESUMO

MOTIVATION: Cellular behavior is determined by complex non-linear interactions between numerous intracellular molecules that are often represented by Boolean network models. To achieve a desired cellular behavior with minimal intervention, we need to identify optimal control targets that can drive heterogeneous cellular states to the desired phenotypic cellular state with minimal node intervention. Previous attempts to realize such global stabilization were based solely on either network structure information or simple linear dynamics. Other attempts based on non-linear dynamics are not scalable. RESULTS: Here, we investigate the underlying relationship between structurally identified control targets and optimal global stabilizing control targets based on non-linear dynamics. We discovered that optimal global stabilizing control targets can be identified by analyzing the dynamics between structurally identified control targets. Utilizing these findings, we developed a scalable global stabilizing control framework using both structural and dynamic information. Our framework narrows down the search space based on strongly connected components and feedback vertex sets then identifies global stabilizing control targets based on the canalization of Boolean network dynamics. We find that the proposed global stabilizing control is superior with respect to the number of control target nodes, scalability, and computational complexity. AVAILABILITY AND IMPLEMENTATION: We provide a GitHub repository that contains the DCGS framework written in Python as well as biological random Boolean network datasets (https://github.com/sugyun/DCGS). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Redes Reguladoras de Genes , Dinâmica não Linear , Algoritmos
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