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1.
Nature ; 620(7972): 72-77, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37168015

RESUMO

A recent study demonstrated near-ambient superconductivity in nitrogen-doped lutetium hydride1. This stimulated a worldwide interest in exploring room-temperature superconductivity at low pressures. Here, by using a high-pressure and high-temperature synthesis technique, we have obtained nitrogen-doped lutetium hydride (LuH2±xNy), which has a dark-blue colour and a structure with the space group [Formula: see text] as evidenced by X-ray diffraction. This structure is the same as that reported in ref. 1, with a slight difference in lattice constant. Raman spectroscopy of our samples also showed patterns similar to those observed in ref. 1. Energy-dispersive X-ray spectroscopy confirmed the presence of nitrogen in the samples. We observed a metallic behaviour from 350 K to 2 K at ambient pressure. On applying pressures from 2.1 GPa to 41 GPa, we observed a gradual colour change from dark blue to violet to pink-red. By measuring the resistance at pressures ranging from 0.4 GPa to 40.1 GPa, we observed a progressively improved metallic behaviour; however, superconductivity was not observed above 2 K. Temperature dependence of magnetization at high pressure shows a very weak positive signal between 100 K and 320 K, and the magnetization increases with an increase in magnetic field at 100 K. All of these are not expected for superconductivity above 100 K. Thus, we conclude the absence of near-ambient superconductivity in this nitrogen-doped lutetium hydride at pressures below 40.1 GPa.

2.
Mol Psychiatry ; 28(2): 611-624, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36224257

RESUMO

Adolescent stress is a risk factor for schizophrenia. Emerging evidence suggests that age-dependent sensitive windows for childhood trauma are associated more strongly with adult psychosis, but the neurobiological basis and potential sex differences are unknown.Using in vivo electrophysiology and immunohistology in rats, we systematically compared the effects of two age-defined adolescent stress paradigms, prepubertal (postnatal day [PD] 21-30; PreP-S) and postpubertal (PD41-50; PostP-S) foot-shock and restraint combined stress, on ventral tegmental area (VTA) dopaminergic activity, pyramidal neuron activity in the ventral hippocampus (vHipp) and the basolateral amygdala (BLA), corticoamygdalar functional inhibitory control, and vHipp and BLA parvalbumin interneuron (PVI) impairments. These endpoints were selected based on their well-documented roles in the pathophysiology of psychosis.Overall, we found distinct sex- and exposure age-dependent stress vulnerability. Specifically, while males were selectively vulnerable to PreP-S-induced adult VTA dopamine neuron and vHipp hyperactivities, females were selectively vulnerable to PostP-S. These male selective PreP-S effects were correlated with stress-induced aberrant persistent BLA hyperactivity, dysfunctional prefrontal inhibitory control of BLA neurons, and vHipp/BLA PVI impairments. In contrast, female PostP-S only produced vHipp PVI impairments in adults, with the BLA structure and functions largely unaffected.Our results indicated distinct adolescent-sensitive periods during which stress can sex-dependently confer maximal risks to corticolimbic systems to drive dopamine hyperactivity, which provide critical insights into the neurobiological basis for sex-biased stress-related psychopathologies emphasizing but not limited to schizophrenia. Furthermore, our work also provides a framework for future translational research on age-sensitive targeted interventions.


Assuntos
Dopamina , Área Tegmentar Ventral , Ratos , Feminino , Masculino , Animais , Dopamina/farmacologia , Ratos Sprague-Dawley , Hipocampo , Neurônios Dopaminérgicos/fisiologia
3.
Mol Psychiatry ; 26(12): 7679-7689, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34193975

RESUMO

Recent evidence showed thalamic abnormalities in schizophrenia involving disruptions to the parvalbumin neurons in the thalamic reticular nucleus (TRN). However, their functional consequences, as well as a potential linkage to oxidative stress, are unclear. The TRN is posited to gate prefrontal control of dopamine neuron activity in the ventral tegmental area (VTA). Thus, we hypothesized that schizophrenia-related TRN abnormalities might contribute to dopamine dysregulation, a well-known feature of the disorder. To test this, in adult rats exposed prenatally to methylazoxymethanol acetate (MAM rats), oxidative impairments to the parvalbumin neurons in the anterior TRN were assessed by immunohistochemistry. Using in vivo electrophysiology, we investigated whether inactivation of the prefrontal cortex would produce differential effects on VTA dopamine neurons in MAM rats. We show that MAM rats displayed reduced markers of parvalbumin and wisteria floribunda agglutinin-labeled perineuronal nets, correlating with increased markers of oxidative stress (8-oxo-7, 8-dihydro-20-deoxyguanosine, and 3-nitrotyrosine). Moreover, MAM rats displayed heightened baseline and abnormal prefrontal control of VTA dopamine neuron activity, as tetrodotoxin-induced inactivation of the infralimbic prefrontal cortex decreased the dopamine population activity, contrary to the normal increase in controls. Such dopamine neuron dysregulation was recapitulated by enzymatic perineuronal net digestion in the TRN of normal rats. Furthermore, juvenile (postnatal day 11-25) antioxidant treatment (N-acetyl-cysteine, 900 mg/L drinking water) prevented all these impairments in MAM rats. Our findings suggest that early accumulation of oxidative stress in the TRN may shape the later onset of schizophrenia pathophysiology, highlighting redox regulation as a potential target for early intervention.


Assuntos
Dopamina , Esquizofrenia , Acetilcisteína/farmacologia , Animais , Modelos Animais de Doenças , Dopamina/farmacologia , Neurônios Dopaminérgicos/fisiologia , Acetato de Metilazoximetanol/farmacologia , Ratos , Núcleos Talâmicos
4.
Mol Psychiatry ; 26(8): 4066-4084, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33235333

RESUMO

Valproate (VPA) has been used in the treatment of bipolar disorder since the 1990s. However, the therapeutic targets of VPA have remained elusive. Here we employ a preclinical model to identify the therapeutic targets of VPA. We find compounds that inhibit histone deacetylase proteins (HDACs) are effective in normalizing manic-like behavior, and that class I HDACs (e.g., HDAC1 and HDAC2) are most important in this response. Using an RNAi approach, we find that HDAC2, but not HDAC1, inhibition in the ventral tegmental area (VTA) is sufficient to normalize behavior. Furthermore, HDAC2 overexpression in the VTA prevents the actions of VPA. We used RNA sequencing in both mice and human induced pluripotent stem cells (iPSCs) derived from bipolar patients to further identify important molecular targets. Together, these studies identify HDAC2 and downstream targets for the development of novel therapeutics for bipolar mania.


Assuntos
Células-Tronco Pluripotentes Induzidas , Ácido Valproico , Animais , Histona Desacetilase 2/genética , Inibidores de Histona Desacetilases/farmacologia , Humanos , Mania , Camundongos , Ácido Valproico/farmacologia
5.
Mol Psychiatry ; 25(12): 3449, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31562399

RESUMO

A correction to this paper has been published and can be accessed via a link at the top of the paper.

6.
Mol Psychiatry ; 25(12): 3278-3291, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-31488866

RESUMO

Unregulated stress during critical periods of development is proposed to drive deficits consistent with schizophrenia in adults. If accurate, reopening the critical period could make the adult susceptible to pathology. We evaluated the impact of early adolescent and adult stress exposure (combination of daily footshock for 10 days and 3 restraint sessions) on (1) midbrain dopamine (DA) neuron activity, (2) ventral hippocampal (vHipp) pyramidal neuron activity, and (3) the number of parvalbumin (PV) interneurons in the vHipp and their associated perineuronal nets (PNNs). Ventral tegmental area (VTA) DA neuron population activity and vHipp activity was increased 1-2 and 5-6 weeks post-adolescent stress, along with a decrease in the number of PV+, PNN+, PV + /PNN + cells in the vHipp, which are consistent with the MAM model of schizophrenia. In contrast, adult stress decreased VTA DA neuron population activity only at 1-2 weeks post stress, which is consistent with what has been observed in animal models of depression, without impacting vHipp activity and PV/PNN expression. Administration of valproate (VPA), which can re-instate the critical period of plasticity via histone deacetylase (HDAC) inhibition, caused adult stress to produce changes similar to those induced by adolescent stress, presumably by increasing stress vulnerability to early adolescent levels. Our findings indicate that timing of stress is a critical determinant of the pathology produced in the adult: adolescent stress led to circuit deficits that recapitulates schizophrenia, whereas adult stress induced a depression-like hypodopaminergic state. Reopening the critical period in the adult restores vulnerability to stress-induced pathology resembling schizophrenia.


Assuntos
Dopamina , Esquizofrenia , Animais , Interneurônios , Parvalbuminas , Área Tegmentar Ventral
7.
J Clin Lab Anal ; 35(2): e23595, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32978843

RESUMO

BACKGROUND: Monocyte-to-high-density lipoprotein (M/H) ratio has emerged as a novel cardiovascular prognostic biomarker. We aimed to evaluate the prognostic values of M/H with early recurrence in persistent valvular atrial fibrillation (AF) patients after radiofrequency (RF) maze procedure. METHODS: We retrospectively analyzed 131 consecutive persistent AF patients with valvular heart diseases who were followed up 3 months after RF maze procedure. Their clinical data were recorded. Logistic regression analyses were performed for significant predictors. Receiver operating characteristic analysis was used for validation with corresponding area under the curve. RESULTS: 70 (53.4%) patients experienced early recurrence after procedure. Patients with early recurrence were older, have longer AF duration history, larger left atria diameter (LAD), higher plasma C-reactive protein (CRP), lower triglycerides (TG), lower cholesterol (TC), increased monocyte counts, lower HDL cholesterol, and increased M/H ratio. In multivariate analysis, age (OR 1.1 95% CI 1.0-1.1 P = .003), LAD (OR 2.1, 95%CI 1.2-3.5, P = .006), TG (OR 0.35, 95% CI 0.15-0.84, P = .019), M/H (OR 6.1, 95% CI 2.9-13.0, P < .001) were significantly independent predictors of AF early recurrence. M/H ratio demonstrated a significant predictive value (AUC = 0.77, sensitivity 89.0%, specificity 54%). Further, there was a positive correlation of M/H ratio with CRP and white blood cell. CONCLUSION: Preoperative M/H ratio was an independent risk factor of AF early recurrence following RF maze operation. M/H ratio should be considered in prediction of early recurrence for valvular AF patients.


Assuntos
Fibrilação Atrial/sangue , Fibrilação Atrial/cirurgia , HDL-Colesterol/sangue , Monócitos/fisiologia , Idoso , Fibrilação Atrial/etiologia , Feminino , Humanos , Masculino , Procedimento do Labirinto , Pessoa de Meia-Idade , Análise Multivariada , Período Pré-Operatório , Prognóstico , Curva ROC , Fatores de Risco , Resultado do Tratamento
8.
Heart Surg Forum ; 24(6): E968-E976, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34962479

RESUMO

BACKGROUND: Atrial fibrillation (AF) recurrence after ablation will increase mortality and morbidity during follow up. We attempted to evaluate the relationship between circular RNAs (circRNA) and AF recurrence to establish a predictive model for early intervention. METHODS: Patients who received surgical ablation retrospectively were analyzed. The expression of circRNAs were detected in the left atrial appendage. The independent risk factors of late recurrence were analyzed by multivariate analysis. The predictive model was visualized by Nomogram and tested by receiver operating characteristic curve and calibration plot. Kaplan-Meier plot was used to compare the rate of freedom from AF recurrence after surgery. The relationships between circRNAs and clinical characteristics were detected by Spearman's correlation analysis. RESULTS: A total of 136 patients were enrolled from September 2018 to June 2019, 55 patients experienced late recurrence during one-year follow up. Increased age, longer AF duration and increased circ 81906-RYR2, circ 44782-LAMA2, circ 418-KCNN2 and circ 35880-ANO5 were detected in recurrent patients. Multivariate analysis revealed that increased age (odds ratio (OR)=1.072, P = 0.006), longer AF duration (OR=1.007, P = 0.036) and increased circ 81906-RYR2 (OR=2.210, P < 0.001) were independent risk factors for late recurrence. Area under the curve was 0.77, and the cut-off value was 70 points of the predictive model. Kaplan-Meier plots showed that patients over 70 points tended to experience AF recurrence. CONCLUSION: Circ 81906-RYR2 could be a new predictor of late recurrence after surgical ablation. A predictive model consists of age, atrial fibrillation duration, and circ 81906-RYR2 was alternative for early intervention of AF recurrence.


Assuntos
Apêndice Atrial , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Ablação por Cateter , RNA Circular/genética , Fatores Etários , Idoso , Fibrilação Atrial/genética , Biomarcadores , Feminino , Seguimentos , Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nomogramas , Curva ROC , Recidiva , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
9.
Mol Psychiatry ; 24(11): 1668-1684, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-29728703

RESUMO

The diurnal regulation of dopamine is important for normal physiology and diseases such as addiction. Here we find a novel role for the CLOCK protein to antagonize CREB-mediated transcriptional activity at the tyrosine hydroxylase (TH) promoter, which is mediated by the interaction with the metabolic sensing protein, Sirtuin 1 (SIRT1). Additionally, we demonstrate that the transcriptional activity of TH is modulated by the cellular redox state, and daily rhythms of redox balance in the ventral tegmental area (VTA), along with TH transcription, are highly disrupted following chronic cocaine administration. Furthermore, CLOCK and SIRT1 are important for regulating cocaine reward and dopaminergic (DAergic) activity, with interesting differences depending on whether DAergic activity is in a heightened state and if there is a functional CLOCK protein. Taken together, we find that rhythms in cellular metabolism and circadian proteins work together to regulate dopamine synthesis and the reward value for drugs of abuse.


Assuntos
Ritmo Circadiano/fisiologia , Sirtuína 1/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo , Animais , Encéfalo/metabolismo , Proteínas CLOCK/genética , Proteínas CLOCK/metabolismo , Ritmo Circadiano/genética , Cocaína/metabolismo , Condicionamento Operante/fisiologia , Condicionamento Psicológico/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NAD/metabolismo , Neurônios/metabolismo , Núcleo Accumbens/metabolismo , Oxirredução , Recompensa , Sirtuína 1/fisiologia , Tirosina 3-Mono-Oxigenase/fisiologia , Área Tegmentar Ventral/metabolismo
10.
Heart Surg Forum ; 23(3): E300-E304, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32524969

RESUMO

BACKGROUND: Electrical cardioversion (ECV) often is required for terminating recurrent atrial fibrillation (AF) after surgical radiofrequency ablation in patients undergoing mitral valve surgery. However, ECV is unsuccessful in some cases. In this study, we aimed to identify possible predictors of failed ECV for recurrent atrial fibrillation following mitral valve surgery with concomitant radiofrequency ablation. METHODS: We enrolled 1,136 persistent AF patients with history of mitral valve surgery and concomitant radiofrequency ablation. Three-hundred-nineteen patients experienced recurrence of persistent AF and received ECV therapy. Comparison was made between patients with failed ECV (Failure group, N = 68) and successful ECV (Success group, N = 251). RESULTS: In multivariate regression analysis, age, pre-ECV loading-dose amiodarone, left atrial diameter, atrial flutter and time from surgery to ECV were independent predictors for outcomes of ECV. According to receiver operating characteristic curve analysis, the best threshold values of age, left atrial diameter and time from surgery to ECV for predicting failed ECV were 55.5 years, 64.5 mm, and 90.5 days, respectively. CONCLUSION: Older age, larger left atrium and longer time from surgery to ECV are independent predictors for failed ECV in this group. Compared with AF, atrial flutter is easier to be successfully terminated by ECV. Pre-ECV loading-dose amiodarone is helpful for successful ECV. These findings have important implications for identifying the kinds of patients to receive effective ECV.


Assuntos
Fibrilação Atrial/terapia , Ablação por Cateter/métodos , Cardioversão Elétrica/efeitos adversos , Doenças das Valvas Cardíacas/complicações , Implante de Prótese de Valva Cardíaca/efeitos adversos , Valva Mitral/cirurgia , Fibrilação Atrial/etiologia , Feminino , Seguimentos , Doenças das Valvas Cardíacas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Falha de Tratamento
11.
Sensors (Basel) ; 20(14)2020 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-32708096

RESUMO

To detect the stress of steel structures and members using the existing magnetism, a magnetic stress sensing system integrating a magnetic flux induction coil, a magnetic flux measurement device, a loaded device, and data acquisition software was developed. The magnetic coupling test research was carried out for different grades of structural building and bridge steel specimens to establish the magnetic stress flux mathematical model, and the fitting equation of the magnetic flux changes with the positions of different sections of specimens was analyzed. Furthermore, a practical formula for stress detection was obtained through the experiments. Meanwhile, on these bases, the typical steel truss structure model of a Bailey beam was designed and manufactured under different working conditions, nondestructive online stress testing was carried out, and the stress of the model structure and its members was measured by strain and magnetic flux tests to obtain the curves of the test results for the stress-strain and magnetic stress flux, respectively. The results of these two methods are in good agreement with each other. The stress of the steel truss model structure was analyzed and calculated using the finite element method. The results agreed well with the experimental results from the magnetic stress sensing system-the maximum error was about 5%, which meets the requirements of engineering applications.

12.
J Neurochem ; 143(3): 264-267, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28872674

RESUMO

This Editorial highlights an article by Gulchina and colleagues in the current issue of the Journal of Neurochemistry, in which the authors describe molecular and epigenetic changes in the developing prefrontal cortex of the rats exposed to methylazoxymethanol acetate (MAM). They found an NMDAR hypofunction present in the prefrontal cortex of juvenile MAM rats which was associated with abnormal epigenetic regulation of the Grin2b gene. These changes may be related to early cognitive impairments observed in MAM rats and schizophrenia patients.


Assuntos
Epigênese Genética/efeitos dos fármacos , Acetato de Metilazoximetanol/toxicidade , Neurotoxinas/toxicidade , Córtex Pré-Frontal , Efeitos Tardios da Exposição Pré-Natal , Esquizofrenia/etiologia , Animais , Modelos Animais de Doenças , Feminino , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/crescimento & desenvolvimento , Córtex Pré-Frontal/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos , Esquizofrenia/patologia
13.
Phys Rev Lett ; 113(18): 186402, 2014 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-25396384

RESUMO

In layered superconductors the order parameter may be modulated within the unit cell, leading to nontrivial modifications of the vortex core if the interlayer coherence length ξ(c)(T) is comparable to the interlayer spacing. In the iron pnictide SmFeAs(O,F) (T(c)≈50 K) this occurs below a crossover temperature T(⋆)≈41 K, which separates two regimes of vortices: anisotropic Abrikosov-like at high and Josephson-like at low temperatures. Yet in the transition region around T(⋆), hybrid vortices between these two characteristics appear. Only in this region around T(⋆) and for magnetic fields well aligned with the FeAs layers, we observe oscillations of the c-axis critical current j(c)(H) periodic in 1/sqrt[H] due to a delicate balance of intervortex forces and interaction with the layered potential. j(c)(H) shows pronounced maxima when a hexagonal vortex lattice is commensurate with the underlying crystal structure. The narrow temperature window in which oscillations are observed suggests a significant suppression of the order parameter between the superconducting layers in SmFeAs(O,F), despite its low coherence length anisotropy (γ(ξ)≈3-5).

14.
Adv Mater ; 36(8): e2309182, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38037474

RESUMO

Storage systems are vital components of electronic devices, while significant challenges persist in achieving flexible memory due to the limitations of existing storage methodologies. Inspired by the polarization and depolarization mechanisms in the human brain, here a novel class of storage principles is proposed and achieve a fully flexible memory through introducing the oxidation and deoxidation behaviors of liquid metals. Specifically, reversible electrochemical oxidation is utilized to modulate the overall conductivity of the target liquid metals, creating a substantial 11-order resistance difference for binary data storage. To obtain the best storage performance, systematic optimizations of multiple parameters are conducted. Conceptual experiments demonstrate the memory's stability under extreme deformations (100% stretching, 180° bending, 360° twisting). Further tests reveal that the memory performs better when its unit size gets smaller, warranting superior integrability. Finally, a complete storage system achieves remarkable performance metrics, including rapid storage speed (>33 Hz), long data retention capacity (>43200 s), and stable repeatable operation (>3500 cycles). This groundbreaking method not only overcomes the inherent rigidity limitations of existing electronic storage units but also opens new possibilities for innovating neuromorphic devices, offering fundamental and practical avenues for future applications in soft robotics, wearable electronics, and bio-inspired artificial intelligence systems.

15.
J Mater Chem B ; 12(9): 2313-2323, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38268450

RESUMO

As a multifunctional material, gallium-based liquid metal (LM) mixtures with metal particles dispersed in the LM environment display many excellent and intriguing properties. In this study, biomaterials were prepared by mixing Fe particles with LM for easily manageable photothermal or electromagnetic therapy and evaluated. Clinically, the fabricated 5%Fe/LM sample was injectable and radiopaque, which allowed its smooth delivery through a syringe to the target tissues, where it could help achieve clear imaging under CT. Meanwhile, because of the loading of Fe particles, the 5%Fe/LM possessed a magnetic property, implying a high manipulation capability. According to the experiments, the capsule containing 5%Fe/LM when placed in an isolated pig large intestine could move as desired to the designated position through an external magnet. Further, the biosafety and low toxicity of the 5%Fe/LM were confirmed by cytotoxicity tests in vitro, and the temperature changes at the interface between the 5%Fe/LM and intestinal tissue after near-infrared (NIR) laser irradiation were determined through theoretical modeling and numerical simulation data analysis. Due to the excellent photothermal and magnetothermal effects of LM, the temperature of the 5%Fe/LM injected into the rabbit abdominal cavity could significantly increase under NIR laser or alternating magnetic field (AMF) administration. As a novel functional biomaterial, the 5%Fe/LM exhibited promising potential for designated position movement and photothermal or magnetothermal therapy in the near future.


Assuntos
Gálio , Magnetoterapia , Animais , Coelhos , Suínos , Materiais Biocompatíveis , Campos Magnéticos
16.
Transl Res ; 267: 54-66, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38199433

RESUMO

Atrial cardiomyopathy (ACM) forms the substrate for atrial fibrillation (AF) and underlies the potential for atrial thrombus formation and subsequent stroke. However, generating stable animal models that accurately replicate the entire progression of atrial lesions, particularly the onset of AF, presents significant challenges. In the present study, we found that the isoform of CRE-binding protein modulator (CREM-IbΔC-X), which is involved in the regulation of cardiac development and atrial rhythm, was highly expressed in atrial biopsies from patients with AF. Building upon this finding, we employed CRISPR/Cas9 technology to create a mouse model with cardiac-specific overexpression of CREM-IbΔC-X (referred to as CS-CREM mice). This animal model effectively illustrated the development of ACM through electrophysiological and structural remodelings over time. Proteomics and Chip-qPCR analysis of atrial samples revealed significant upregulation of cell-matrix adhesion and extracellular matrix structural components, alongside significant downregulation of genes related to atrial functions in the CS-CREM mice. Furthermore, the corresponding responses to anti-arrhythmia drugs, i.e., amiodarone and propafenone, suggested that CS-CREM mice could serve as an ideal in vivo model for drug testing. Our study introduced a novel ACM model with spontaneous AF by cardiac-specifically overexpressing CREM-IbΔC-X in mice, providing valuable insights into the mechanisms and therapeutic targets of ACM.


Assuntos
Fibrilação Atrial , Cardiomiopatias , Camundongos , Humanos , Animais , Sistemas CRISPR-Cas/genética , Camundongos Transgênicos , Átrios do Coração/patologia , Cardiomiopatias/genética , Modulador de Elemento de Resposta do AMP Cíclico/genética , Modulador de Elemento de Resposta do AMP Cíclico/metabolismo
17.
Sci Adv ; 10(21): eadp5215, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38787948

RESUMO

Multi-stimulus responsive soft materials with integrated functionalities are elementary blocks for building soft intelligent systems, but their rational design remains challenging. Here, we demonstrate an intelligent soft architecture sensitized by magnetized liquid metal droplets that are dispersed in a highly stretchable elastomer network. The supercooled liquid metal droplets serve as microscopic latent heat reservoirs, and their controllable solidification releases localized thermal energy/information flows for enabling programmable visualization and display. This allows the perception of a variety of information-encoded contact (mechanical pressing, stretching, and torsion) and noncontact (magnetic field) stimuli as well as the visualization of dynamic phase transition and stress evolution processes, via thermal and/or thermochromic imaging. The liquid metal-elastomer architecture offers a generic platform for designing soft intelligent sensing, display, and information encryption systems.

18.
Aging Cell ; 23(3): e14074, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38155547

RESUMO

Delirium is the most common neurological complication after cardiac surgery with adverse impacts on surgical outcomes. Advanced age is an independent risk factor for delirium occurrence but its underlying mechanisms are not fully understood. Although increased A1 astrocytes and abnormal hippocampal networks are involved in neurodegenerative diseases, whether A1 astrocytes and hippocampal network changes are involved in the delirium-like behavior of aged mice remains unknown. In the present study, a mice model of myocardial ischemia-reperfusion mimicking cardiac surgery and various assessments were used to investigate the different susceptibility of the occurrence of delirium-like behavior between young and aged mice and the underlying mechanisms. The results showed that surgery significantly increased hippocampal A1 astrocyte activation in aged compared to young mice. The high neuroinflammatory state induced by surgery resulted in glutamate accumulation in the extrasynaptic space, which subsequently decreased the excitability of pyramidal neurons and increased the PV interneurons inhibition through enhancing N-methyl-D-aspartate receptors' tonic currents in the hippocampus. These further induced the abnormal activities of the hippocampal neural networks and consequently contributed to delirium-like behavior in aged mice. Notably, the intraperitoneal administration of exendin-4, a glucagon-like peptide-1 receptor agonist, downregulated A1 astrocyte activation and alleviated delirium-like behavior in aged mice, while IL-1α, TNF-α, and C1q in combination administered intracerebroventricularly upregulated A1 astrocyte activation and induced delirium-like behavior in young mice. Therefore, our study suggested that cardiac surgery increased A1 astrocyte activation which subsequently impaired the hippocampal neural networks and triggered delirium development.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Delírio , Camundongos , Animais , Astrócitos , Hipocampo/fisiologia , Redes Neurais de Computação
19.
Biosensors (Basel) ; 13(6)2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37366968

RESUMO

Capacitive sensors are essential to promoting modernization and intelligence in agriculture. With the continuous advancement of this sensor technology, the demand for materials with high conductivity and flexibility is rapidly increasing. Herein, we introduce liquid metal as a solution for the in-site fabrication of high-performance capacitive sensors for plant sensing. As a comparison, three pathways have been proposed for the preparation of flexible capacitors inside plants, as well as on their surfaces. Specifically, concealed capacitors can be constructed by directly injecting liquid metal into the plant cavity. Printable capacitors are prepared via printing Cu-doped liquid metal with better adhesion on plant surfaces. A composite liquid metal-based capacitive sensor is achieved by printing liquid metal on the plant surface and injecting it into the interior of the plant. While each method has limitations, the composite liquid metal-based capacitive sensor provides an optimal trade-off between signal capture capability and operability. As a result, this composite capacitor is chosen as a sensor for monitoring water changes within plants and demonstrates the desired sensing performance, making it a promising technology for monitoring plant physiology.


Assuntos
Agricultura , Inteligência , Condutividade Elétrica , Metais , Impressão
20.
Adv Healthc Mater ; 12(7): e2202872, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36515112

RESUMO

Innovations on materials and technologies have greatly promoted the rapid development of wearable electronics from disease diagnosis to therapeutics. For superficial skin tumors, skin-attachable patches possess the advantages of minimally invasive property, alleviative side effects, and high efficiency. The development of noninvasive techniques and devices is still in urgent demands. Here, a flexible skin patch fabricated through a facile preparation method is reported for noninvasive hybrid thermophysical therapy and adaptative immune function enhancement. The liquid metal enabled skin patch is demonstrated with high conductivity, certain stability, biocompatibility, and an enhanced adhesive merit on skin surfaces for cryoablation therapy and magnetic hyperthermia therapy. The skin patch exhibits remarkably conformable heating and cooling performance toward the treatment of 4T1 breast tumors. The magnetic resonance images also indicate the significant tumor ablation effect. Interestingly, a relatively stable proportion of both CD8+ T and CD4+ T cells in the peripheral blood is identified after tumor therapy in comparison with the decreased trend in the untreated group, representing an efficient antitumor immune response induced by the skin patch. The developed skin patch would provide a promising noninvasive approach for tumor therapies by direct tumor destruction and maintenance of the antitumor immune response.


Assuntos
Hipertermia Induzida , Neoplasias Cutâneas , Dispositivos Eletrônicos Vestíveis , Humanos , Adesivo Transdérmico , Imunidade
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