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1.
J Neuroinflammation ; 21(1): 113, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38685031

RESUMO

Obesity increases the morbidity and mortality of traumatic brain injury (TBI). Detailed analyses of transcriptomic changes in the brain and adipose tissue were performed to elucidate the interactive effects between high-fat diet-induced obesity (DIO) and TBI. Adult male mice were fed a high-fat diet (HFD) for 12 weeks prior to experimental TBI and continuing after injury. High-throughput transcriptomic analysis using Nanostring panels of the total visceral adipose tissue (VAT) and cellular components in the brain, followed by unsupervised clustering, principal component analysis, and IPA pathway analysis were used to determine shifts in gene expression patterns and molecular pathway activity. Cellular populations in the cortex and hippocampus, as well as in VAT, during the chronic phase after combined TBI-HFD showed amplification of central and peripheral microglia/macrophage responses, including superadditive changes in selected gene expression signatures and pathways. Furthermore, combined TBI and HFD caused additive dysfunction in Y-Maze, Novel Object Recognition (NOR), and Morris water maze (MWM) cognitive function tests. These novel data suggest that HFD-induced obesity and TBI can independently prime and support the development of altered states in brain microglia and VAT, including the disease-associated microglia/macrophage (DAM) phenotype observed in neurodegenerative disorders. The interaction between HFD and TBI promotes a shift toward chronic reactive microglia/macrophage transcriptomic signatures and associated pro-inflammatory disease-altered states that may, in part, underlie the exacerbation of cognitive deficits. Thus, targeting of HFD-induced reactive cellular phenotypes, including in peripheral adipose tissue immune cell populations, may serve to reduce microglial maladaptive states after TBI, attenuating post-traumatic neurodegeneration and neurological dysfunction.


Assuntos
Lesões Encefálicas Traumáticas , Encéfalo , Disfunção Cognitiva , Dieta Hiperlipídica , Macrófagos , Camundongos Endogâmicos C57BL , Microglia , Animais , Dieta Hiperlipídica/efeitos adversos , Microglia/metabolismo , Microglia/patologia , Masculino , Camundongos , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/patologia , Disfunção Cognitiva/metabolismo , Macrófagos/metabolismo , Macrófagos/patologia , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas Traumáticas/metabolismo , Encéfalo/patologia , Encéfalo/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Reconhecimento Psicológico/fisiologia , Obesidade/patologia , Obesidade/complicações , Aprendizagem em Labirinto/fisiologia
2.
J Neuroinflammation ; 21(1): 83, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38581043

RESUMO

BACKGROUND: It is well established that traumatic brain injury (TBI) causes acute and chronic alterations in systemic immune function and that systemic immune changes contribute to posttraumatic neuroinflammation and neurodegeneration. However, how TBI affects bone marrow (BM) hematopoietic stem/progenitor cells chronically and to what extent such changes may negatively impact innate immunity and neurological function has not been examined. METHODS: To further understand the role of BM cell derivatives on TBI outcome, we generated BM chimeric mice by transplanting BM from chronically injured or sham (i.e., 90 days post-surgery) congenic donor mice into otherwise healthy, age-matched, irradiated CD45.2 C57BL/6 (WT) hosts. Immune changes were evaluated by flow cytometry, multiplex ELISA, and NanoString technology. Moderate-to-severe TBI was induced by controlled cortical impact injury and neurological function was measured using a battery of behavioral tests. RESULTS: TBI induced chronic alterations in the transcriptome of BM lineage-c-Kit+Sca1+ (LSK+) cells in C57BL/6 mice, including modified epigenetic and senescence pathways. After 8 weeks of reconstitution, peripheral myeloid cells from TBI→WT mice showed significantly higher oxidative stress levels and reduced phagocytic activity. At eight months after reconstitution, TBI→WT chimeric mice were leukopenic, with continued alterations in phagocytosis and oxidative stress responses, as well as persistent neurological deficits. Gene expression analysis revealed BM-driven changes in neuroinflammation and neuropathology after 8 weeks and 8 months of reconstitution, respectively. Chimeric mice subjected to TBI at 8 weeks and 8 months post-reconstitution showed that longer reconstitution periods (i.e., time post-injury) were associated with increased microgliosis and leukocyte infiltration. Pre-treatment with a senolytic agent, ABT-263, significantly improved behavioral performance of aged C57BL/6 mice at baseline, although it did not attenuate neuroinflammation in the acutely injured brain. CONCLUSIONS: TBI causes chronic activation and progressive dysfunction of the BM stem/progenitor cell pool, which drives long-term deficits in hematopoiesis, innate immunity, and neurological function, as well as altered sensitivity to subsequent brain injury.


Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Camundongos , Animais , Doenças Neuroinflamatórias , Camundongos Endogâmicos C57BL , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas/patologia , Encéfalo/metabolismo
3.
Brain Behav Immun ; 120: 584-603, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38986724

RESUMO

Aged individuals with spinal cord injury (SCI) are prevalent with increased mortality and worse outcomes. SCI can cause secondary brain neuroinflammation and neurodegeneration. However, the mechanisms contributing to SCI-induced brain dysfunction are poorly understood. Cell-to-cell signaling through extracellular vesicles (EVs) has emerged as a critical mediator of neuroinflammation, including at a distance through circulation. We have previously shown that SCI in young adult (YA) male mice leads to robust changes in plasma EV count and microRNAs (miRs) content. Here, our goal was to investigate the impact of old age on EVs and brain after SCI. At 24 h post-injury, there was no difference in particle count or size distribution between YA and aged mice. However, aged animals increased expression of EV marker CD63 with SCI. Using the Fireplex® miRs assay, Proteomics, and mass spectrometry-based Lipidomics, circulating EVs analysis identified distinct profiles of miRs, proteins, and lipid components in old and injury animals. In vitro, plasma EVs from aged SCI mice, at a lower concentration comparable to those of YA SCI mice, induced the secretion of pro-inflammatory cytokines and neuronal apoptosis. Systemic administration of plasma EVs from SCI animals was sufficient to impair general physical function and neurological function in intact animals, which is associated with pro-inflammatory changes in the brain. Furthermore, plasma EVs from young animals had rejuvenating effects on naïve aged mice. Collectively, these studies identify the critical changes in circulating EVs cargoes after SCI and in aged animals and support a potential EV-mediated mechanism for SCI-induced brain changes.


Assuntos
Envelhecimento , Encéfalo , Vesículas Extracelulares , Doenças Neuroinflamatórias , Traumatismos da Medula Espinal , Animais , Vesículas Extracelulares/metabolismo , Masculino , Camundongos , Doenças Neuroinflamatórias/metabolismo , Traumatismos da Medula Espinal/metabolismo , Encéfalo/metabolismo , Envelhecimento/metabolismo , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Citocinas/metabolismo , Citocinas/sangue , Neurônios/metabolismo , Inflamação/metabolismo
4.
Angew Chem Int Ed Engl ; 63(3): e202316385, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38010600

RESUMO

The diversification of chirality in covalent organic frameworks (COFs) holds immense promise for expanding their properties and functionality. Herein, we introduce an innovative approach for imparting helical chirality to COFs and fabricating a family of chiral COF nanotubes with mesoscopic helicity from entirely achiral building blocks for the first time. We present an effective 2,3-diaminopyridine-mediated supramolecular templating method, which facilitates the prefabrication of helical imine-linked polymer nanotubes using unprecedented achiral symmetric monomers. Through meticulous optimization of crystallization conditions, these helical polymer nanotubes are adeptly converted into imine-linked COF nanotubes boasting impressive surface areas, while well preserving their helical morphology and chiroptical properties. Furthermore, these helical imine-linked polymers or COFs could be subtly transformed into corresponding more stable and functional helical ß-ketoenamine-linked and hydrazone-linked COF nanotubes with transferred circular dichroism via monomer exchange. Notably, despite the involvement of covalent bonding breakage and reorganization, these exchange processes overcome thermodynamic disadvantages, allowing mesoscopic helical chirality to be perfectly preserved. This research highlights the potential of mesoscopic helicity in conferring COFs with favourable chiral properties, providing novel insights into the development of multifunctional COFs in the field of chiral materials chemistry.

5.
J Neuroinflammation ; 20(1): 197, 2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37653491

RESUMO

BACKGROUND: Medical advances have made it increasingly possible for spinal cord injury (SCI) survivors to survive decades after the insult. But how SCI affects aging changes and aging impacts the injury process have received limited attention. Extracellular vesicles (EVs) are recognized as critical mediators of neuroinflammation after CNS injury, including at a distance from the lesion site. We have previously shown that SCI in young male mice leads to robust changes in plasma EV count and microRNA (miR) content. Here, our goal was to investigate the impact of biological sex and aging on EVs and brain after SCI. METHODS: Young adult age-matched male and female C57BL/6 mice were subjected to SCI. At 19 months post-injury, total plasma EVs were isolated by ultracentrifugation and characterized by nanoparticle tracking analysis (NTA). EVs miR cargo was examined using the Fireplex® assay. The transcriptional changes in the brain were assessed by a NanoString nCounter Neuropathology panel and validated by Western blot (WB) and flow cytometry (FC). A battery of behavioral tests was performed for assessment of neurological function. RESULTS: Transcriptomic changes showed a high number of changes between sham and those with SCI. Sex-specific changes were found in transcription networks related to disease association, activated microglia, and vesicle trafficking. FC showed higher microglia and myeloid counts in the injured tissue of SCI/Female compared to their male counterparts, along with higher microglial production of ROS in both injured site and the brain. In the latter, increased levels of TNF and mitochondrial membrane potential were seen in microglia from SCI/Female. WB and NTA revealed that EV markers are elevated in the plasma of SCI/Male. Particle concentration in the cortex increased after injury, with SCI/Female showing higher counts than SCI/Male. EVs cargo analysis revealed changes in miR content related to injury and sex. Behavioral testing confirmed impairment of cognition and depression at chronic time points after SCI in both sexes, without significant differences between males and females. CONCLUSIONS: Our study is the first to show sexually dimorphic changes in brain after very long-term SCI and supports a potential sex-dependent EV-mediated mechanism that contributes to SCI-induced brain changes.


Assuntos
Doenças Neuroinflamatórias , Traumatismos da Medula Espinal , Feminino , Masculino , Animais , Camundongos , Camundongos Endogâmicos C57BL , Encéfalo , Traumatismos da Medula Espinal/complicações , Cognição
6.
Small ; 19(42): e2303131, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37344349

RESUMO

Fabrication of large-area ionic covalent organic framework membranes (iCOMs) remains a grand challenge. Herein, the authors report the liquid water and water vapor-assisted fabrication of large-area superprotonic conductive iCOMs. A mixed monomer solution containing 1,3,5-triformylphloroglucinol (TFP) in 1,4-dioxane and p-diaminobenzenesulfonic acid (DABA) in water is first polymerized to obtain a pristine membrane which subsequently underwent crystallization process in mixed vapors containing water vapor. During the polymerization stage, water played a role of a diluting agent, weakening the Coulombic repulsion between sulfonic acid groups. During the crystallization stage, water vapor played a role of a structure-directing agent to facilitate the formation of highly crystalline, large-area iCOMs. The resulting membranes achieved a proton conductivity value of 0.76 S cm-1 at 90 °C under 100% relative humidity, which is among the highest ever reported. Using liquid water and water vapor as versatile additives open a novel avenue to the fabrication of large-area membranes from covalent organic frameworks and other kinds of crystalline organic framework materials.

7.
Langmuir ; 39(39): 13953-13967, 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37729118

RESUMO

MXene is an incredibly promising two-dimensional material with immense potential to serve as a high-performing separating or barrier layer to develop advanced membranes. Despite the significant progress made in MXene membranes, two major challenges still exist: (i) effectively stacking MXene nanosheets into defect-free membranes and (ii) the high fouling tendency of MXene-based membranes. To address these issues, we employed sulfonated polydopamine (SPD), which simultaneously serves as a binding agent to promote the compact assembling of Ti3C2Tx MXenes (MX) nanosheets and improves the antifouling properties of the resulting sulfonated polydopamine-functionalized MX (SPDMX) membranes. The SPDMX membrane was tested for challenging surfactant-stabilized oil-in-water separation with an impressive efficiency of 98%. Moreover, an ultrahigh permeability of 1620 LMH/bar was also achieved. The sulfonation of PD helps in improving the antifouling characteristics of SPDMX by developing a strong hydration layer and enhancing the oleophobicity of the membrane. The underwater SPDMX membrane appeared superoleophobic with an oil contact angle of 153°, whereas the ceramic membrane exhibited an oil contact angle of 137°. The SPDMX membranes showed an improved flux recovery (31%) compared to the nonsulfonated counterpart. This work highlights the appropriate functionalization of MXene as a promising approach to developing MXene membranes with high permeation flux and better antifouling characteristics for oily wastewater treatment.

8.
Glia ; 69(3): 746-764, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33090575

RESUMO

Acidosis is among the least studied secondary injury mechanisms associated with neurotrauma. Acute decreases in brain pH correlate with poor long-term outcome in patients with traumatic brain injury (TBI), however, the temporal dynamics and underlying mechanisms are unclear. As key drivers of neuroinflammation, we hypothesized that microglia directly regulate acidosis after TBI, and thereby, worsen neurological outcomes. Using a controlled cortical impact model in adult male mice we demonstrate that intracellular pH in microglia and extracellular pH surrounding the lesion site are significantly reduced for weeks after injury. Microglia proliferation and production of reactive oxygen species (ROS) were also increased during the first week, mirroring the increase in extracellular ROS levels seen around the lesion site. Microglia depletion by a colony stimulating factor 1 receptor (CSF1R) inhibitor, PLX5622, markedly decreased extracellular acidosis, ROS production, and inflammation in the brain after injury. Mechanistically, we identified that the voltage-gated proton channel Hv1 promotes oxidative burst activity and acid extrusion in microglia. Compared to wildtype controls, microglia lacking Hv1 showed reduced ability to generate ROS and extrude protons. Importantly, Hv1-deficient mice exhibited reduced pathological acidosis and inflammation after TBI, leading to long-term neuroprotection and functional recovery. Our data therefore establish the microglial Hv1 proton channel as an important link that integrates inflammation and acidosis within the injury microenvironment during head injury.


Assuntos
Acidose , Lesões Encefálicas Traumáticas , Animais , Lesões Encefálicas Traumáticas/complicações , Humanos , Inflamação , Canais Iônicos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Doenças Neuroinflamatórias , Prótons , Espécies Reativas de Oxigênio/metabolismo , Explosão Respiratória
9.
Brain Behav Immun ; 92: 165-183, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33307173

RESUMO

Extracellular vesicles (EVs) have been implicated mechanistically in the pathobiology of neurodegenerative disorders, including central nervous system injury. However, the role of EVs in spinal cord injury (SCI) has received limited attention to date. Moreover, technical limitations related to EV isolation and characterization methods can lead to misleading or contradictory findings. Here, we examined changes in plasma EVs after mouse SCI at multiple timepoints (1d, 3d, 7d, 14d) using complementary measurement techniques. Plasma EVs isolated by ultracentrifugation (UC) were decreased at 1d post-injury, as shown by nanoparticle tracking analysis (NTA), and paralleled an overall reduction in total plasma extracellular nanoparticles. Western blot (WB) analysis of UC-derived plasma EVs revealed increased expression of the tetraspanin exosome marker, CD81, between 1d and 7d post-injury. To substantiate these findings, we performed interferometric and fluorescence imaging of single, tetraspanin EVs captured directly from plasma with ExoView®. Consistent with WB, we observed significantly increased plasma CD81+ EV count and cargo at 1d post-injury. The majority of these tetraspanin EVs were smaller than 50 nm based on interferometry and were insufficiently resolved by flow cytometry-based detection. At the injury site, there was enhanced expression of EV biogenesis proteins that were also detected in EVs directly isolated from spinal cord tissue by WB. Surface expression of tetraspanins CD9 and CD63 increased in multiple cell types at the injury site; however, astrocyte CD81 expression uniquely decreased, as demonstrated by flow cytometry. UC-isolated plasma EV microRNA cargo was also significantly altered at 1d post-injury with changes similar to that reported in EVs released by astrocytes after inflammatory stimulation. When injected into the lateral ventricle, plasma EVs from SCI mice increased both pro- and anti-inflammatory gene as well as reactive astrocyte gene expression in the brain cortex. These studies provide the first detailed characterization of plasma EV dynamics after SCI and suggest that plasma EVs may be involved in posttraumatic brain inflammation.


Assuntos
Exossomos , Vesículas Extracelulares , MicroRNAs , Nanopartículas , Traumatismos da Medula Espinal , Animais , Camundongos
10.
Angew Chem Int Ed Engl ; 60(33): 18051-18058, 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34062042

RESUMO

Covalent organic framework (COF) membranes hold potential for widespread applicability, but scalable fabrication is challenging. Here, we demonstrate the disorder-to-order transformation from amorphous polymeric membrane to crystalline COF membrane via monomer exchange. Solution processing is used to prepare amorphous membrane and the replacing monomer is selected based on the chemical and thermodynamical stability of the final framework. Reversible imine bonds allow the extraneous monomers to replace the pristine monomers within amorphous membrane, driving the transformation from disordered network to ordered framework. Incorporation of intramolecular hydrogen bonds enables the crystalline COF to imprint the amorphous membrane morphology. The COF membranes harvest proton conductivity up to 0.53 S cm-1 at 80 °C. Our strategy bridges amorphous polymeric and crystalline COF membranes for large-scale fabrication of COF membranes and affords guidance on materials processing.

11.
J Am Chem Soc ; 142(31): 13450-13458, 2020 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-32649828

RESUMO

Covalent organic frameworks (COFs) with intrinsic, tunable, and uniform pores are potent building blocks for separation membranes, yet poor processing ability and long processing time remain grand challenges. Herein, we report an engineered solid-vapor interface to fabricate a highly crystalline two-dimensional COF membrane with a thickness of 120 nm in 9 h, which is 8 times faster than that in the reported literature. Due to the ultrathin nature and ordered pores, the membrane exhibited an ultrahigh permeance (water, ∼411 L m-2 h-1 bar-1 and acetonitrile, ∼583 L m-2 h-1 bar-1) and excellent rejection of dye molecules larger than 1.4 nm (>98%). The membrane exhibited long-term operation which confirmed its outstanding stability. Our solid-vapor interfacial polymerization method may evolve into a generic platform to fabricate COFs and other organic framework membranes.

12.
Neurobiol Dis ; 136: 104713, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31843705

RESUMO

Traumatic brain injury (TBI) can cause progressive neurodegeneration, sustained neuroinflammation and chronic neurological dysfunction. Few experimental studies have explored the long-term neurobehavioral and functional cellular changes beyond several months. The present study examined the effects of a single moderate-level TBI on functional outcome 8 months after injury. Male C57BL/6 mice were subjected to controlled cortical impact injury and followed for changes in motor performance, learning and memory, as well as depressive-like and social behavior. We also used a novel flow cytometry approach to assess cellular functions in freshly isolated neurons and microglia from the injured tissue. There were marked and diverse, sustained neurobehavioral changes in injured mice. Compared to sham controls, chronic TBI mice showed long-term deficits in gait dynamics, nest building, spatial working memory and recognition memory. The tail suspension, forced swim, and sucrose consumption tests showed a marked depressive-like phenotype that was associated with impaired sociability. At the cellular level, there were lower numbers of Thy1+Tuj1+ neurons and higher numbers of activated CD45loCD11b+ microglia. Functionally, both neurons and microglia exhibited significantly higher levels of oxidative stress after injury. Microglia exhibited chronic deficits in phagocytosis of E. coli bacteria, and increased uptake of myelin and dying neurons. Living neurons showed decreased expression of synaptophysin and postsynaptic density (PSD)-95, along with greater numbers of microtubule-associated protein light chain 3 (LC3)-positive autophagosomes and increased mitochondrial mass that suggest dysregulation of autophagy. In summary, the late neurobehavioral changes found after murine TBI are similar to those found chronically after moderate-severe human head injury. Importantly, such changes are associated with microglial dysfunction and changes in neuronal activity.


Assuntos
Lesões Encefálicas/fisiopatologia , Lesões Encefálicas/psicologia , Transtornos Mentais/fisiopatologia , Transtornos Mentais/psicologia , Microglia/patologia , Neurônios/patologia , Animais , Lesões Encefálicas/complicações , Masculino , Aprendizagem em Labirinto/fisiologia , Transtornos Mentais/etiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Interação Social , Fatores de Tempo
13.
J Neuroinflammation ; 14(1): 47, 2017 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-28292310

RESUMO

BACKGROUND: Local and systemic inflammatory responses are initiated early after traumatic brain injury (TBI), and may play a key role in the secondary injury processes resulting in neuronal loss and neurological deficits. However, the mechanisms responsible for the rapid expansion of neuroinflammation and its long-term progression have yet to be elucidated. Here, we investigate the role of microparticles (MP), a member of the extracellular vesicle family, in the exchange of pro-inflammatory molecules between brain immune cells, as well as their transfer to the systemic circulation, as key pathways of inflammation propagation following brain trauma. METHODS: Adult male C57BL/6 mice were subjected to controlled cortical impact TBI for 24 h, and enriched MP were isolated in the blood, while neuroinflammation was assessed in the TBI cortex. MP were characterized by flow cytometry, and MP content was assayed using gene and protein markers for pro-inflammatory mediators. Enriched MP co-cultured with BV2 or primary microglial cells were used for immune propagation assays. Enriched MP from BV2 microglia or CD11b-positive microglia from the TBI brain were stereotactically injected into the cortex of uninjured mice to evaluate MP-related seeding of neuroinflammation in vivo. RESULTS: As the neuroinflammatory response is developing in the brain after TBI, microglial-derived MP are released into the circulation. Circulating enriched MP from the TBI animals can activate microglia in vitro. Lipopolysaccharide stimulation increases MP release from microglia in vitro and enhances their content of pro-inflammatory mediators, interleukin-1ß and microRNA-155. Enriched MP from activated microglia in vitro or CD11b-isolated microglia/macrophage from the TBI brain ex vivo are sufficient to initiate neuroinflammation following their injection into the cortex of naïve (uninjured) animals. CONCLUSIONS: These data provide further insights into the mechanisms underlying the development and dissemination of neuroinflammation after TBI. MP loaded with pro-inflammatory molecules initially released by microglia following trauma can activate additional microglia that may contribute to progressive neuroinflammatory response in the injured brain, as well as stimulate systemic immune responses. Due to their ability to independently initiate inflammatory responses, MP derived from activated microglia may provide a potential therapeutic target for other neurological disorders in which neuroinflammation may be a contributing factor.


Assuntos
Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/patologia , Micropartículas Derivadas de Células/metabolismo , Encefalite/etiologia , Microglia/metabolismo , Animais , Antígeno CD11b/metabolismo , Linhagem Celular Transformada , Técnicas de Cocultura , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Encefalite/sangue , Leucócitos/química , Leucócitos/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , Microglia/química , Microglia/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , RNA Mensageiro/metabolismo , Receptores Purinérgicos P2Y12/metabolismo
14.
Chem Commun (Camb) ; 60(14): 1811-1825, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38264768

RESUMO

The advancement of highly efficient and enduring platinum (Pt)-based electrocatalysts for the oxygen reduction reaction (ORR) is a critical determinant to enable broad utilization of clean energy conversion technologies. Pt-based intermetallic electrocatalysts offer durability and superior ORR activity over their traditional analogues due to their definite stoichiometry, ordered and extended structures, and favourable enthalpy of formation. With the advent in new synthetic methods, Pt-based intermetallic nanoparticles as a new class of advanced electrocatalysts have been studied extensively in recent years. This review discusses the preparation principles, representative preparation methods of Pt-based intermetallics and their applications in the ORR. Our review is focused on L10 Pt-based intermetallics which have gained tremendous interest recently due to their larger surface strain and enhanced M(3d)-Pt(5d) orbital coupling, particularly in the crystallographic c-axis direction. Additionally, we discuss future research directions to further improve the efficiency of Pt-based intermetallic electrocatalysts with the intention of stimulating increased research ventures in this domain.

15.
Phys Rev E ; 109(6-2): 065311, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39020893

RESUMO

The understanding of quantum phase transitions in disordered or quasicrystal media is a central issue in condensed matter physics. In this paper we investigate localization properties of the two-dimensional Aubry-André model. We find that the system exhibits self-duality for the transformation between position and momentum spaces at a critical quasiperiodic potential, leading to an energy-independent Anderson transition. Most importantly, we present the implementation of an efficient and accurate algorithm based on the Chebyshev polynomial expansion of the Loschmidt echo, which characterizes the nonequilibrium dynamics of quantum quenched quasiperiodic systems. We analytically prove that the system under quench dynamics displays dynamical quantum phase transitions and further provide numerical verification by computing the polynomial expansion of the Loschmidt echo. Our results may provide insight into the realization of electronic transport in experiments.

16.
J Chromatogr A ; 1734: 465311, 2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39226749

RESUMO

The inorganic matrices such as metal concentrates, steel, cement, glass, clay, coal, graphite, rocks and sediments, ores etc. play a pivotal role in infrastructure development, transportation, and energy. The presence of non-metallic elements particularly halogens influence their quality, processing cost, and environment dynamics. The analysis of non-metals in such matrices is critically challenging due to their hardness, rigidity, and non-digestibility. This comprehensive review provides a critical comparison of various sample preparation methods in conjunction with pros and cons of advanced techniques for the detection of non-metals in complex matrices, particularly focusing on ion chromatography. Moreover, the review also addresses the challenges related to the enrichment and automation of non-metals analysis. In addition, the previous literature on non-metals determination in diverse range of inorganic matrices has been tabulated for the first time. These insights are intended to guide researchers, quality control analysts, environmental scientists, and policymakers in enhancing pollution monitoring and control strategies.


Assuntos
Halogênios , Halogênios/análise , Halogênios/química , Cromatografia por Troca Iônica/métodos , Monitoramento Ambiental/métodos
17.
Heliyon ; 10(17): e36771, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39319147

RESUMO

The geometry, electronic structure, and adsorption properties of halogen molecule X2(X = F, Cl) on arsenene were investigated using first-principles calculations. The adsorption of molecules was considered at various sites and in various orientations on the pristine arsenene (p-As) surface. Both molecules show chemisorption and the crystal orbital Hamiltonian population (COHP) analysis reveals the formation of strong X-As bonds. In particular, the adsorbed molecules spontaneously dissociate into atomic halogen atoms, with a diffusion barrier of 1.91 (1.72) eV for F2(Cl2). The adsorbed X2 molecules induced distortions in the local geometry due to strong interaction with arsenene. Importantly, the formation of X-As bonding remarkably changed the electronic properties, evidenced by the decrease of the actual band gap due to the emergence of defect states within the band gap. For instance, the F2 adsorbed arsenene system (F2-As) exhibited an average band gap of 1.17 eV, and Cl2 adsorbed arsenene (Cl2-As) showed an average band gap of 0.83 eV. In particular, indirect to direct band gap transition was observed for some adsorption configurations. The reduction in band gap resulted in the enhancement of electrical conductivity. These findings suggest that the electronic properties of arsenene can be tuned by halogen decoration.

18.
Med Eng Phys ; 124: 104095, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38418024

RESUMO

Rehabilitation is a major requirement to improve the quality of life and mobility of patients with disabilities. The use of rehabilitative devices without continuous supervision of medical experts is increasing manifold, mainly due to prolonged therapy costs and advancements in robotics. Due to ExoMechHand's inexpensive cost, high robustness, and efficacy for participants with median and ulnar neuropathies, we have recommended it as a rehabilitation tool in this study. ExoMechHand is coupled with three different resistive plates for hand impairment. For efficacy, ten unhealthy subjects with median or ulnar nerve neuropathies are considered. After twenty days of continuous exercise, three subjects showed improvement in their hand grip, range of motion of the wrist, or range of motion of metacarpophalangeal joints. The condition of the hand is assessed by features of surface-electromyography signals. A Machine-learning model based on these features of fifteen subjects is used for staging the condition of the hand. Machine-learning algorithms are trained to indicate the type of resistive plate to be used by the subject without the need for examination by the therapist. The extra-trees classifier came out to be the most effective algorithm with 98% accuracy on test data for indicating the type of resistive plate, followed by random-forest and gradient-boosting with accuracies of 95% and 93%, respectively. Results showed that the staging of hand condition could be analyzed by sEMG signal obtained from the flexor-carpi-ulnaris and flexor-carpi-radialis muscles in subjects with median and ulnar neuropathies.


Assuntos
Força da Mão , Neuropatias Ulnares , Humanos , Qualidade de Vida , Punho/fisiologia , Mãos/fisiologia , Eletromiografia
19.
Asian J Psychiatr ; 92: 103897, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38199203

RESUMO

OBJECTIVE: To determine the community prevalence of psychiatric disorders in adult population and describe the prevalence by age, men-women, urban-rural strata. METHODS: A nationwide household survey was conducted in 2019 where adults aged 18 years and above were selected by a multicentric, stratified, systematic random approach. The Self-Reporting Questionnaire (SRQ) was used for screening purpose and screened positive individuals were interviewed by research psychiatrists and diagnosed according the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria. RESULTS: Overall adult response rate for this survey was 90.4%. In total, of the 7270 adults, 1570 (21.6%) came positive on the SRQ. Overall prevalence of mental disorders found was 18.7% ((95% CI: 17.4%-20.0%). Women reported higher prevalence of psychiatric disorders than men (21.5% vs 15.7%). No significant difference was observed between urban and rural residents (18.9% vs 18.7%). Most common psychiatric disorders found were depressive disorders (6.7%), anxiety disorders (4.7%), somatic symptom and related disorders (2.3%), sleep-wake disorders (1%) and schizophrenia spectrum disorders (1%). CONCLUSIONS: The study revealed that a substatial proportion of adults received diagnoses for psychiatric disorders. Once again, our findings emphasize the need for development of comprehensive mental healthcare services.


Assuntos
Transtornos Mentais , Adulto , Masculino , Humanos , Feminino , Prevalência , Bangladesh/epidemiologia , Transtornos Mentais/epidemiologia , Transtornos Mentais/diagnóstico , Transtornos de Ansiedade/epidemiologia , Inquéritos e Questionários
20.
ACS Omega ; 9(23): 25106-25123, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38882164

RESUMO

Lung cancer is a frequently diagnosed respiratory disease caused by particulate matter in the environment, especially among older individuals. For its effective treatment, a promising approach involves administering drug particles through the inhalation route. Multiple studies have investigated the flow behavior of inhaled particles in the respiratory airways of healthy patients. However, the existing literature lacks studies on the precise understanding of the transportation and deposition (TD) of inhaled particles through age-specific, unhealthy respiratory tracts containing a tumor, which can potentially optimize lung cancer treatment. This study aims to investigate the TD of inhaled drug particles within a tumorous, age-specific human respiratory tract. The computational model reports that drug particles within the size range of 5-10 µm are inclined to deposit more on the tumor located in the upper airways of a 70-year-old lung. Conversely, for individuals aged 50 and 60 years, an optimal particle size range for achieving the highest degree of particle deposition onto upper airway tumor falls within the 11-20 µm range. Flow disturbances are found to be at a maximum in the airway downstream of the tumor. Additionally, the impact of varying inhalation flow rates on particle TD is examined. The obtained patterns of airflow distribution and deposition efficiency on the tumor wall for different ages and tumor locations in the upper tracheobronchial airways would be beneficial for developing an efficient and targeted drug delivery system.

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