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1.
J Neurosci ; 44(4)2024 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-38124016

RESUMO

The dorsal raphe nucleus (DRN) is an important nucleus in pain regulation. However, the underlying neural pathway and the function of specific cell types remain unclear. Here, we report a previously unrecognized ascending facilitation pathway, the DRN to the mesoaccumbal dopamine (DA) circuit, for regulating pain. Chronic pain increased the activity of DRN glutamatergic, but not serotonergic, neurons projecting to the ventral tegmental area (VTA) (DRNGlu-VTA) in male mice. The optogenetic activation of DRNGlu-VTA circuit induced a pain-like response in naive male mice, and its inhibition produced an analgesic effect in male mice with neuropathic pain. Furthermore, we discovered that DRN ascending pathway regulated pain through strengthened excitatory transmission onto the VTA DA neurons projecting to the ventral part of nucleus accumbens medial shell (vNAcMed), thereby activated the mesoaccumbal DA neurons. Correspondingly, optogenetic manipulation of this three-node pathway bilaterally regulated pain behaviors. These findings identified a DRN ascending excitatory pathway that is crucial for pain sensory processing, which can potentially be exploited toward targeting pain disorders.


Assuntos
Núcleo Dorsal da Rafe , Área Tegmentar Ventral , Camundongos , Masculino , Animais , Núcleo Dorsal da Rafe/fisiologia , Área Tegmentar Ventral/fisiologia , Neurônios Dopaminérgicos/fisiologia , Núcleo Accumbens , Dor/metabolismo
2.
Opt Lett ; 49(13): 3781-3784, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38950266

RESUMO

We propose a scheme for realizing nonreciprocal microwave photon routing with two cascaded magnon-cavity coupled systems, which work around the exceptional points of a parity-time (PT)-symmetric Hamiltonian. An almost perfect nonreciprocal transmission can be achieved with a broad bandwidth, where the transmission for a forward-propagating photon can be flexibly controlled with the backpropagating photon being isolated. The transmission or isolated direction can be reversed via simply controlling the magnetic field direction applied to the magnons. The isolation bandwidth is improved by almost three times in comparison with the device based on a single PT-symmetric system. Moreover, the effect of intrinsic cavity loss and added thermal noises is considered, confirming the experimental feasibility of the nonreciprocal device and potential applications in quantum information processing.

3.
J Res Adolesc ; 34(2): 410-435, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38797867

RESUMO

This study aimed to generate localized knowledge by investigating the perceptions and experiences of preadolescent grandchildren and grandparents regarding grandparenting and intergenerational interactions and how these processes were related to the social skills of preadolescents from three ethnic groups in Malaysia. Using a concurrent quantitative-qualitative mixed method research design, Chinese, Malay, and Indian preadolescents (N = 465; ages 9-12 years old; M = 10.27 years; SD = 1.03) from rural areas in Malaysia completed a self-administered quantitative survey; furthermore, 25 grandparents participated in one-on-one interviews. Survey findings showed that preadolescent grandchildren who reported higher grandparental warmth and support had greater social skills, mediated by positive grandparent-grandchildren (GP-GC) relationships. The GP-GC relationship and preadolescent social skills association was stronger for skipped generation compared to three-generation households. Interview findings revealed that grandparents expressed unconditional love and autonomy support in their grandparenting roles by guiding and encouraging their preadolescent grandchildren to make decisions. The GP-GC interactions served as a dynamic force in promoting preadolescents' social skills. By employing a decolonized approach and drawing on the lived experiences of grandparents from three ethnic backgrounds in rural Malaysia, the study provided an understanding of grandparenting practices and their general implications across the three ethnic groups. The interview responses highlighted both commonalities and specificities in grandparenting practices and relationship dynamics shaped by religious, class, and sociocultural dimensions in rural Malaysia.


Assuntos
Avós , Relação entre Gerações , População Rural , Habilidades Sociais , Humanos , Malásia/etnologia , Avós/psicologia , Relação entre Gerações/etnologia , Masculino , Criança , Feminino
4.
J Neurosci ; 42(14): 3049-3064, 2022 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-35197318

RESUMO

Anxiety disorders are a series of mental disorders characterized by anxiety and fear, but the molecular basis of these disorders remains unclear. In the present study, we find that the global Slack KO male mice exhibit anxious behaviors, whereas the Slack Y777H male mice manifest anxiolytic behaviors. The expression of Slack channels is rich in basolateral amygdala (BLA) glutamatergic neurons and downregulated in chronic corticosterone-treated mice. In addition, electrophysiological data show enhanced excitability of BLA glutamatergic neurons in the Slack KO mice and decreased excitability of these neurons in the Slack Y777H mice. Furthermore, the Slack channel deletion in BLA glutamatergic neurons is sufficient to result in enhanced avoidance behaviors, whereas Kcnt1 gene expression in the BLA or BLA-ventral hippocampus (vHPC) glutamatergic projections reverses anxious behaviors of the Slack KO mice. Our study identifies the role of the Slack channel in controlling anxious behaviors by decreasing the excitability of BLA-vHPC glutamatergic projections, providing a potential target for anxiolytic therapies.SIGNIFICANCE STATEMENT Anxiety disorders are a series of mental disorders characterized by anxiety and fear, but the molecular basis of these disorders remains unclear. Here, we examined the behaviors of loss- and gain-of-function of Slack channel mice in elevated plus maze and open field tests and found the anxiolytic role of the Slack channel. By altering the Slack channel expression in the specific neuronal circuit, we demonstrated that the Slack channel played its anxiolytic role by decreasing the excitability of BLA-vHPC glutamatergic projections. Our data reveal the role of the Slack channel in the regulation of anxiety, which may provide a potential molecular target for anxiolytic therapies.


Assuntos
Ansiedade , Complexo Nuclear Basolateral da Amígdala , Proteínas do Tecido Nervoso , Canais de Potássio Ativados por Sódio , Animais , Ansiedade/metabolismo , Complexo Nuclear Basolateral da Amígdala/metabolismo , Hipocampo/metabolismo , Masculino , Camundongos , Camundongos Knockout , Proteínas do Tecido Nervoso/metabolismo , Canais de Potássio Ativados por Sódio/metabolismo
5.
J Biol Chem ; 298(9): 102326, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35933015

RESUMO

Atrial fibrillation is the most common sustained cardiac arrhythmia in humans. Current atrial fibrillation antiarrhythmic drugs have limited efficacy and carry the risk of ventricular proarrhythmia. GsMTx4, a mechanosensitive channel-selective inhibitor, has been shown to suppress arrhythmias through the inhibition of stretch-activated channels (SACs) in the heart. The cost of synthesizing this peptide is a major obstacle to clinical use. Here, we studied two types of short peptides derived from GsMTx4 for their effects on a stretch-activated big potassium channel (SAKcaC) from the heart. Type I, a 17-residue peptide (referred to as Pept 01), showed comparable efficacy, whereas type II (i.e., Pept 02), a 10-residue peptide, exerted even more potent inhibitory efficacy on SAKcaC compared with GsMTx4. We identified through mutagenesis important sequences required for peptide functions. In addition, molecular dynamics simulations revealed common structural features with a hydrophobic head followed by a positively charged protrusion that may be involved in peptide channel-lipid interactions. Furthermore, we suggest that these short peptides may inhibit SAKcaC through a specific modification to the mechanogate, as the inhibitory effects for both types of peptides were mostly abolished when tested with a mechano-insensitive channel variant (STREX-del) and a nonmechanosensitive big potassium (mouse Slo1) channel. These findings may offer an opportunity for the development of a new class of drugs in the treatment of cardiac arrhythmia generated by excitatory SACs in the heart.


Assuntos
Antiarrítmicos , Peptídeos e Proteínas de Sinalização Intercelular , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta , Neurotoxinas , Peptídeos , Venenos de Aranha , Animais , Antiarrítmicos/química , Antiarrítmicos/farmacologia , Antiarrítmicos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/química , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/antagonistas & inibidores , Lipídeos , Camundongos , Neurotoxinas/química , Neurotoxinas/farmacologia , Peptídeos/química , Peptídeos/farmacologia , Venenos de Aranha/química , Venenos de Aranha/farmacologia , Venenos de Aranha/uso terapêutico
6.
Opt Express ; 31(6): 9236-9250, 2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-37157497

RESUMO

We study the enhanced sensing of optomechanically induced nonlinearity (OMIN) in a cavity-waveguide coupled system. The Hamiltonian of the system is anti-PT symmetric, with the two involved cavities being dissipatively coupled via the waveguide. The anti-PT symmetry may break down when a weak waveguide-mediated coherent coupling is introduced. However, we find a strong bistable response of the cavity intensity to the OMIN near the cavity resonance, benefiting from linewidth suppression caused by the vacuum induced coherence. The joint effect of optical bistability and the linewidth suppression is inaccessible by the anti-PT symmetric system involving only dissipative coupling. Due to that, the sensitivity measured by an enhancement factor is greatly enhanced by two orders of magnitude compared to that for the anti-PT symmetric model. Moreover, the enhancement factor shows resistance to a reasonably large cavity decay and robustness to fluctuations in the cavity-waveguide detuning. Based on the integrated optomechanical cavity-waveguide systems, the scheme can be used for sensing different physical quantities related to the single-photon coupling strength and has potential applications in high-precision measurements with systems involving Kerr-type nonlinearity.

7.
Calcif Tissue Int ; 113(5): 515-525, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37812222

RESUMO

Due to disturbances in hormones and long-term glucocorticoid replacement therapy (GRT), congenital adrenocortical hyperplasia (CAH) patients are at risk of impaired bone structure and metabolism. This cross-sectional, case-control study aims to investigate for the first time bone microarchitecture features in 21-hydroxylase deficiency (21OHD; N = 38) and 17α-hydroxylase deficiency (17OHD; N = 16) patients using high-resolution peripheral quantitative computed tomography (HR-pQCT) by matching the same sex and similar age [21OHD vs. control: 29.5 (24.0-34.3) vs. 29.6 (25.9-35.2) years; 17OHD vs. controls: 29.0 (21.5-35.0) vs. 29.7 (24.6-35.3) years] with healthy controls (1:3). All patients underwent HR-pQCT scans of the nondominant radius and tibia, and had received GRT. Compared with corresponding controls, 17OHD cases had higher height (P < 0.001), weight (P = 0.013) and similar body mass index (BMI), while 21OHD had lower height (P < 0.001), similar weight and higher BMI (P < 0.001). 17OHD and 21OHD patients demonstrated various significant bone differences in most HR-pQCT indices, suggesting abnormalities in bone microarchitectures from healthy people. Further correlation analyses revealed that some characteristics, such as height and hormones, may contribute to the bone differences in HR-pQCT indices between two diseases. However, treatment dosage and time were not correlated, indicating that the current glucocorticoid doses may be within safety limits for bone impairment. Overall, our study for the first time revealed changes of bone microarchitecture in CAH patients and their potential relations with clinical characteristics. Further longitudinal researches are required to confirm these findings.


Assuntos
Densidade Óssea , Glucocorticoides , Humanos , Estudos Transversais , Estudos de Casos e Controles , Glucocorticoides/uso terapêutico , Glucocorticoides/metabolismo , Minerais/metabolismo , Rádio (Anatomia) , Tíbia , Oxigenases de Função Mista/metabolismo , Absorciometria de Fóton
8.
PLoS Biol ; 18(11): e3000965, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33232322

RESUMO

Near-infrared (NIR) genetically encoded calcium ion (Ca2+) indicators (GECIs) can provide advantages over visible wavelength fluorescent GECIs in terms of reduced phototoxicity, minimal spectral cross talk with visible light excitable optogenetic tools and fluorescent probes, and decreased scattering and absorption in mammalian tissues. Our previously reported NIR GECI, NIR-GECO1, has these advantages but also has several disadvantages including lower brightness and limited fluorescence response compared to state-of-the-art visible wavelength GECIs, when used for imaging of neuronal activity. Here, we report 2 improved NIR GECI variants, designated NIR-GECO2 and NIR-GECO2G, derived from NIR-GECO1. We characterized the performance of the new NIR GECIs in cultured cells, acute mouse brain slices, and Caenorhabditis elegans and Xenopus laevis in vivo. Our results demonstrate that NIR-GECO2 and NIR-GECO2G provide substantial improvements over NIR-GECO1 for imaging of neuronal Ca2+ dynamics.


Assuntos
Cálcio/metabolismo , Imagem Óptica/métodos , Animais , Encéfalo/metabolismo , Caenorhabditis elegans/metabolismo , Corantes Fluorescentes , Proteínas de Fluorescência Verde/química , Proteínas de Fluorescência Verde/genética , Células HeLa , Humanos , Indicadores e Reagentes , Proteínas Luminescentes/química , Proteínas Luminescentes/genética , Camundongos , Miócitos Cardíacos/metabolismo , Neurônios/metabolismo , Optogenética , Engenharia de Proteínas , Espectroscopia de Luz Próxima ao Infravermelho , Xenopus laevis/metabolismo
9.
Phys Chem Chem Phys ; 25(36): 24797-24808, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37671654

RESUMO

Biphenylene networks typically exhibit a metallic electronic nature, while hydrogenation can open the band gap changing it to a semiconductor. This property makes hydrogenated biphenylene a promising candidate for use in semiconductor optoelectronic materials and devices. In this work, three representative configurations of hydrogenated biphenylene, denoted by α, ß and γ, were investigated. The structural, mechanical, electronic, and optical properties of these hydrogenated biphenylene configurations were calculated by first-principles calculations. Band gaps with HSE correction were 4.69, 4.42 and 4.39 eV for α, ß, and γ configurations, respectively. Among these three configurations, ß presents the best electronic performance and special elastic properties (negative Poisson's ratio), while γ exhibits the best elastic properties. In addition, we comprehensively analyze the mechanical properties of these configurations and provide evidence that hydrogenated biphenylene possibly exhibits a negative-Poisson's-ratio along the zigzag and armchair directions when hydrogen atoms are added to biphenylene in certain ways. Furthermore, although the electronic properties of γ are weaker than those of ß, they are also excellent. In addition, the binding energies of ß and γ are relatively lower, which indicates that ß and γ are more stable. Our findings demonstrate that the hydrogenated biphenylene is a promising material with significant application potential in optoelectronic devices.

10.
Br J Anaesth ; 130(4): 446-458, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36737387

RESUMO

BACKGROUND: Corticotropin-releasing factor (CRF) neurones in the paraventricular nucleus (PVN) of the hypothalamus (PVNCRF neurones) can promote wakefulness and are activated under anaesthesia. However, whether these neurones contribute to anaesthetic effects is unknown. METHODS: With a combination of chemogenetic and molecular approaches, we examined the roles of PVNCRF neurones in isoflurane anaesthesia in mice and further explored the underlying cellular and molecular mechanisms. RESULTS: PVN neurones exhibited increased Fos expression during isoflurane anaesthesia (mean [standard deviation], 218 [69.3] vs 21.3 [7.3]; P<0.001), and ∼75% were PVNCRF neurones. Chemogenetic inhibition of PVNCRF neurones facilitated emergence from isoflurane anaesthesia (11.7 [1.1] vs 13.9 [1.2] min; P=0.001), whereas chemogenetic activation of these neurones delayed emergence from isoflurane anaesthesia (16.9 [1.2] vs 13.9 [1.3] min; P=0.002). Isoflurane exposure increased CRF protein expression in PVN (4.0 [0.1] vs 2.2 [0.3], respectively; P<0.001). Knockdown of CRF in PVNCRF neurones mimicked the effects of chemogenetic inhibition of PVNCRF neurones in facilitating emergence (9.6 [1.1] vs 13.0 [1.4] min; P=0.003) and also abolished the effects of chemogenetic activation of PVNCRF neurones on delaying emergence from isoflurane anaesthesia (10.3 [1.3] vs 16.0 [2.6] min; P<0.001). Acute, but not chronic, stress delayed emergence from isoflurane anaesthesia (15.5 [1.5] vs 13.0 [1.4] min; P=0.004). This effect was reversed by chemogenetic inhibition of PVNCRF neurones (11.7 [1.6] vs 14.7 [1.4] min; P=0.001) or knockdown of CRF in PVNCRF neurones (12.3 [1.5] vs 15.3 [1.6] min; P=0.002). CONCLUSIONS: CRF neurones in the PVN of the hypothalamus neurones modulate isoflurane anaesthesia and acute stress effects on anaesthesia through CRF signalling.


Assuntos
Anestesia , Isoflurano , Camundongos , Animais , Hormônio Liberador da Corticotropina/metabolismo , Hormônio Liberador da Corticotropina/farmacologia , Núcleo Hipotalâmico Paraventricular/metabolismo , Isoflurano/farmacologia , Hipotálamo/metabolismo
11.
Am J Occup Ther ; 77(6)2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-38048263

RESUMO

IMPORTANCE: The efficacy of telehealth (TH) interventions needs to be studied. OBJECTIVE: To compare the efficacy, fidelity, acceptability, and feasibility of face-to-face (F2F) versus TH seated play (SP) interventions among children with autism spectrum disorder (ASD). DESIGN: As part of a larger randomized controlled trial, children were assigned to the SP group and received TH and F2F interventions over 8 wk using a pretest-posttest study design. SETTING: A research lab or through videoconferencing. PARTICIPANTS: Fifteen children with ASD (ages 5-14 yr) were randomly assigned to the SP group and received the intervention F2F or through TH. INTERVENTION: Children received 16 SP intervention sessions (2 sessions per week for 8 wk). OUTCOMES AND MEASURES: Pretests and posttests included standardized fine motor assessments. Video coding compared socially directed verbalization during training sessions. Parents and trainers provided feedback on their experiences. RESULTS: Seven children received the intervention F2F, whereas 8 received TH intervention. Children in both subgroups showed similar training improvements in fine motor skills and socially directed verbalizations (ps > .01). Parents rated both interventions as acceptable and feasible; however, they reported longer preparation time and effort during TH interventions (ps < .01). Trainers reported greater parental involvement but more communication and technological issues during TH interventions. Fidelity checks indicated fewer reinforcements during TH versus F2F sessions. CONCLUSIONS AND RELEVANCE: TH intervention is feasible and effective in improving fine motor and social communication performance. Clinicians should reduce parental burden and overcome technological issues. What This Article Adds: This study confirmed the efficacy, fidelity, acceptability, and feasibility of delivering seated play, standard of care interventions for children with autism spectrum disorder via telehealth. However, clinicians should work on reducing parental burden and overcoming communication and technological issues related to telehealth.


Assuntos
Transtorno do Espectro Autista , Telemedicina , Criança , Humanos , Transtorno do Espectro Autista/terapia , Comunicação , Estudos de Viabilidade , Pais/educação , Pré-Escolar , Adolescente
12.
J Neurosci ; 41(48): 9988-10003, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34642215

RESUMO

Long-term limb nerve injury often leads to mirror-image pain (MIP), an abnormal pain sensation in the limb contralateral to the injury. Although it is clear that MIP is mediated in part by central nociception processing, the underlying mechanisms remain poorly understood. The anterior cingulate cortex (ACC) is a key brain region that receives relayed peripheral nociceptive information from the contralateral limb. In this study, we induced MIP in male mice, in which a unilateral chronic constrictive injury of the sciatic nerve (CCI) induced a decreased nociceptive threshold in both hind limbs and an increased number of c-Fos-expressing neurons in the ACC both contralateral and ipsilateral to the injured limb. Using viral-mediated projection mapping, we observed that a portion of ACC neurons formed monosynaptic connections with contralateral ACC neurons. Furthermore, the number of cross-callosal projection ACC neurons that exhibited c-Fos signal was increased in MIP-expressing mice, suggesting enhanced transmission between ACC neurons of the two hemispheres. Moreover, selective inhibition of the cross-callosal projection ACC neurons contralateral to the injured limb normalized the nociceptive sensation of the uninjured limb without affecting the increased nociceptive sensation of the injured limb in CCI mice. In contrast, inhibition of the non-cross-callosal projection ACC neurons contralateral to the injury normalized the nociceptive sensation of the injured limb without affecting the MIP exhibited in the uninjured limb. These results reveal a circuit mechanism, namely, the cross-callosal projection of ACC between two hemispheres, that contributes to MIP and possibly other forms of contralateral migration of pain sensation.SIGNIFICANCE STATEMENT Mirror-image pain (MIP) refers to the increased pain sensitivity of the contralateral body part in patients with chronic pain. This pathology requires central processing, yet the mechanisms are less known. Here, we demonstrate that the cross-callosal projection neurons in the anterior cingulate cortex (ACC) contralateral to the injury contribute to MIP exhibited in the uninjured limb, but do not affect nociceptive sensation of the injured limb. In contrast, the non-cross-callosal projection neurons in the ACC contralateral to the injury contribute to nociceptive sensation of the injured limb, but do not affect MIP exhibited in the uninjured limb. Our study depicts a novel cross-callosal projection of ACC that contributes to MIP, providing a central mechanism for MIP in chronic pain state.


Assuntos
Lateralidade Funcional/fisiologia , Giro do Cíngulo/fisiopatologia , Neuralgia/fisiopatologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neuralgia/etiologia
13.
Opt Lett ; 47(5): 1182-1185, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35230322

RESUMO

Nonreciprocal transmission of optical or microwave signals is indispensable in various applications involving sensitive measurements. In this paper, we study optomechanically induced directional amplification and isolation in a generic setup including two cavities and two mechanical oscillators by exclusively using blue-sideband drive tones. The input and output ports defined by the two cavity modes are coupled through coherent and dissipative paths mediated by the two mechanical resonators, respectively. By choosing appropriate transfer phases and strengths of the driving fields, either a directional amplifier or an isolator can be implemented at low thermal temperature, and both of them show bi-directional nonreciprocity working at two mirrored frequencies. The nonreciprocal device can potentially be demonstrated by opto- and electromechanical setups in both optical and microwave domains.

14.
Langmuir ; 38(3): 1045-1056, 2022 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-35020400

RESUMO

When a dry mass of certain amphiphiles encounters water, a spectacular interfacial instability ensues: It gives rise to the formation of ensembles of fingerlike tubular protrusions called myelin figures─tens of micrometers wide and tens to hundreds of micrometers long─representing a novel class of nonequilibrium higher-order self-organization. Here, we report that when phase-separating mixtures of unsaturated lipid, cholesterol, and sphingomyelin are hydrated, the resulting myelins break symmetry and couple their compositional degrees of freedom with the extended myelinic morphology: They produce complementary, interlamellar radial gradients of concentrations of cholesterol (and sphingomyelin) and unsaturated lipid, which stands in stark contrast to interlamellar, lateral phase separation in equilibrated morphologies. Furthermore, the corresponding gradients of molecule-specific chemistries (i.e., cholesterol extraction by methyl-ß-cyclodextrin and GM1 binding by cholera toxin) produce unusual morphologies comprising compositionally graded vesicles and buckled tubes. We propose that kinetic differences in the information processing of hydration characteristics of individual molecules while expending energy dictate this novel behavior of lipid mixtures undergoing hydration.


Assuntos
Bicamadas Lipídicas , Esfingomielinas , Fenômenos Biofísicos , Colesterol
15.
Langmuir ; 38(24): 7545-7557, 2022 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-35671406

RESUMO

Molecular dynamics (MD) simulations in the MARTINI model are used to study the assembly of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) molecules under spatial confinement, such as during solvent evaporation from ultrasmall (femtoliter quantity) droplets. The impact of surface polarity on molecular assembly is discussed in detail. To the best of our knowledge, this work represents the first of its kind. Our results reveal that solvent evaporation gives rise to the formation of well-defined stacks of lipid bilayers in a smectic alignment. These smectic mesophases form on both polar and nonpolar surfaces but with a notable distinction. On polar surfaces, the director of the stack is oriented perpendicular to the support surface. By contrast, the stacks orient at an angle on the nonpolar surfaces. The packing of head groups on surfaces and lipid molecular mobility exhibits significant differences as surface polarity changes. The role of glycerol in the assembly and stability is also revealed. The insights revealed from the simulation have a significant impact on additive manufacturing, biomaterials, model membranes, and engineering protocells. For example, POPC assemblies via evaporation of ultrasmall droplets were produced and characterized. The trends compare well with the bilayer stack models. The surface polarity influences the local morphology and structures at the interfaces, which could be rationalized via the molecule-surface interactions observed from simulations.


Assuntos
Bicamadas Lipídicas , Fosfatidilcolinas , Bicamadas Lipídicas/química , Simulação de Dinâmica Molecular , Fosfatidilcolinas/química , Solventes
16.
Cell Biol Toxicol ; 38(4): 629-648, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34677723

RESUMO

Aristolochic acid nephropathy (AAN) is a progressive kidney disease caused by some herbal medicines, but treatment remains ineffective. We previously found that leucine-rich α-2-glycoprotein 1 (LRG1), which regulates cellular processes, plays an important role in a kidney injury model. However, the underlying mechanism by which LRG1 regulates AAN is still unknown. In this study, we established an AAN model in vivo, a coculture system of macrophages and TECs, and a macrophage/TEC conditioned media culture model in vitro. We found that macrophage infiltration promoted injury, oxidative stress, and apoptosis in TECs. Furthermore, the role of macrophages in AAN was dependent on macrophage-derived extracellular vesicles (EVs). Importantly, we found that macrophage-derived, LRG1-enriched EVs induced TEC injury and apoptosis via a TGFßR1-dependent process. This study may help design a better therapeutic strategy to treat AAN patients.


Assuntos
Vesículas Extracelulares , Nefropatias , Animais , Ácidos Aristolóquicos , Modelos Animais de Doenças , Glicoproteínas , Humanos , Nefropatias/induzido quimicamente , Macrófagos
17.
Phys Chem Chem Phys ; 24(26): 16310-16316, 2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35758594

RESUMO

Direct-band silicon materials have been a sought-after material for potential applications in silicon photonics and solar cells. Accordingly, methodologies like nanostructure engineering, alloy engineering and strain engineering have been developed. In this work, the particle swarm optimization (PSO) algorithm is used to design direct-band Si-Ge alloys. The findings of phonon computations demonstrate that all these structures are dynamically stable. In addition, ab initio molecular dynamics and elastic constant calculations are carried out, with results indicating these structures are thermodynamically stable at 300 K, as well as being mechanically stable. All of these materials exhibit semiconductor behavior with band gaps of 1.03, 0.68 and 1.37 eV for α, ß and γ phases, respectively, at the HSE06 level. The results of effective mass and mobility of carriers that are important in applications show that holes are more easily transported in all structures, with higher concentration of holes accompanied by lower carrier mobility. Different concentrations of holes nh lead to different limits in the scattering process. When nh is lower than the value of around 1016 cm-3, deformation potential scattering is dominant, while the ionized impurity scattering process limits overall mobility when nh is higher than such a value. Finally, the absorption spectra shows that both α and ß phases have isotropic optical properties in the X- and Y-directions while strong anisotropy can be seen in the Z-direction. However, the γ phase exhibits no notable isotropy. This investigation finds three direct-band and potentially CMOS compatible materials, a finding which will benefit the development of high efficiency emitters or solar cells.

18.
J Clin Periodontol ; 49(10): 970-979, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35634696

RESUMO

AIM: Tinnitus, ringing in the ears, is speculated to be driven by inflammation. This study examined whether periodontitis is a risk factor for tinnitus using Taiwan's National Health Insurance Research Database. MATERIALS AND METHODS: Among the 79,456 patients who visited for dental concerns, 11,055 patients who were diagnosed with periodontitis and underwent periodontal treatment between 2000 and 2015 were enrolled in Group 1. After matching for sex, age, and index year, 11,055 patients with periodontitis who received no treatment were enrolled in Group 2. Similarly, 11,055 participants without periodontitis were included as controls. RESULTS: At the end of the follow-up, 412 and 404 participants in the two periodontitis groups and 321 participants in the control group had tinnitus. Cumulative risk for tinnitus in Group 1 or 2 was significantly greater than in the control group. More periodontitis patients than controls developed tinnitus (adjusted hazard ratios were 1.71 (95% confidence interval [CI]: 1.49-1.97, p < .001) and 1.64 (95% CI: 1.37-1.86, p < .001) in Groups 1 and 2, respectively). The risks were not significantly different between Groups 1 and 2. Similar findings were obtained after excluding data for the first 1 or 5 years. CONCLUSIONS: The study findings indicate that periodontitis is associated with tinnitus.


Assuntos
Periodontite , Zumbido , Estudos de Coortes , Humanos , Periodontite/complicações , Periodontite/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia , Zumbido/complicações , Zumbido/epidemiologia
19.
Pediatr Phys Ther ; 34(2): 246-251, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35184077

RESUMO

PURPOSE: After the COVID-19 pandemic, several randomized controlled trials came to a halt; however, we chose to reinvent our study and shifted to a home-based, telehealth intervention delivery format to support children with autism spectrum disorder and their families. Children with autism spectrum disorder have social communication impairments as well as perceptuomotor and cognitive comorbidities. Continued access to care is crucial for their long-term development. METHODS: We created a general movement intervention to target strength, endurance, executive functioning, and social skills through goal-directed games and activities delivered using a telehealth intervention model. FINDINGS: Our family-centered approach allowed for collaboration between trainers and caregivers and made it easy for families to replicate training activities at home. CONCLUSIONS: While more studies comparing telehealth and face-to-face interventions are needed, we encourage researchers and clinicians to consider family-centered telehealth as a valid and feasible intervention delivery method, to increase the likelihood of carryover of skills into the daily lives of children and ultimately enhance their long-term development.


Assuntos
Transtorno do Espectro Autista , COVID-19 , Telemedicina , COVID-19/epidemiologia , Criança , Humanos , Pandemias , Habilidades Sociais
20.
Biophys J ; 120(4): 586-597, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33460597

RESUMO

Single giant unilamellar vesicles (GUVs) rupture spontaneously from their salt-laden suspension onto solid surfaces. At hydrophobic surfaces, the GUVs rupture via a recurrent, bouncing ball rhythm. During each contact, the GUVs, rendered tense by the substrate interactions, porate, and spread a molecularly transformed motif of a monomolecular layer on the hydrophobic surface from the point of contact in a symmetric manner. The competition from pore closure, however, limits the spreading and produces a daughter vesicle, which re-engages with the substrate. At solid hydrophilic surfaces, by contrast, GUVs rupture via a distinctly different recurrent burst-heal dynamics; during burst, single pores nucleate at the contact boundary of the adhering vesicles, facilitating asymmetric spreading and producing a "heart"-shaped membrane patch. During the healing phase, the competing pore closure produces a daughter vesicle. In both cases, the pattern of burst-reseal events repeats multiple times, splashing and spreading the vesicular fragments as bilayer patches at the solid surface in a pulsatory manner. These remarkable recurrent dynamics arise, not because of the elastic properties of the solid surface, but because the competition between membrane spreading and pore healing, prompted by the surface-energy-dependent adhesion, determine the course of the topological transition.


Assuntos
Lipídeos , Lipossomas Unilamelares , Fenômenos Biofísicos , Interações Hidrofóbicas e Hidrofílicas , Bicamadas Lipídicas
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