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1.
Acta Pharm Sin B ; 14(9): 4014-4027, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39309503

RESUMEN

The arginine-vasopressin (AVP) hormone plays a pivotal role in regulating various physiological processes, such as hormone secretion, cardiovascular modulation, and social behavior. Recent studies have highlighted the V1a receptor as a promising therapeutic target. In-depth insights into V1a receptor-related pathologies, attained through in vivo imaging and quantification in both peripheral organs and the central nervous system (CNS), could significantly advance the development of effective V1a inhibitors. To address this need, we develop a novel V1a-targeted positron emission tomography (PET) ligand, [18F]V1A-2303 ([18F]8), which demonstrates favorable in vitro binding affinity and selectivity for the V1a receptor. Specific tracer binding in peripheral tissues was also confirmed through rigorous cell uptake studies, autoradiography, biodistribution assessments. Furthermore, [18F]8 was employed in PET imaging and arterial blood sampling studies in healthy rhesus monkeys to assess its brain permeability and specificity, whole-body distribution, and kinetic properties. Our research indicated [18F]8 as a valuable tool for noninvasively studying V1a receptors in peripheral organs, and as a foundational element for the development of next-generation, brain-penetrant ligands specifically designed for the CNS.

2.
Sci Total Environ ; 953: 176251, 2024 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-39277004

RESUMEN

High coastal nutrient loading can cause changes in seagrass chemistry traits that may lead to variability in seagrass litter decomposition processes. Such changes in decomposition have the potential to alter the carbon (C) sequestration capacity within seagrass meadows ('blue carbon'). However, the external and internal factors that drive the variability in decomposition rates of the different organic matter (OM) types of seagrass are poorly understood, especially recalcitrant OM (i.e. cellulose-associated OM and lignin-associated OM), thereby limiting our ability to evaluate the C sequestration potential. It was conducted a laboratory incubation to compare differences in the decomposition of Halophila beccarii litter collected from seagrass meadows with contrasting nutrient loading histories. The exponential decay constants of seagrass litter mass, cellulose-associated OM and lignin-associated OM were 0.009-0.032, 0.014-0.054 and 0.009-0.033 d-1, respectively. The seagrass litter collected from meadows with high nutrient loading exhibited greater losses of mass (25.0-41.2 %), cellulose-associated OM (2.8-18.5 %) and lignin-associated OM (9.6-31.2 %) than litter from relatively low nutrient loading meadows. The initial and temporal changes of the litter nitrogen (N) and phosphorus (P) concentrations, stoichiometric ratios of lignin/N, C/N, and C/P, and cellulose-associated OM content, were strongly correlated with the losses of litter mass and different types of OM. Further, temporal changes of litter C and OM types, particularly the OM and labile OM concentrations, were identified as the main driving factors for the loss of litter mass and loss of different OM types. These results indicated that nutrient-loaded seagrass litter, characterized by elevated nutrient levels and diminished amounts of recalcitrant OM, exhibits an accelerated decay rate for the recalcitrant OM. These differences in litter quality would lead to a reduced contribution of seagrass litter to long-term C stocks in eutrophic meadows, thereby weakening the stability of C sequestration. Considering the expected changes in seagrass litter chemistry traits and decay rates due to long-term nutrient loading, this study provides useful information for improving C sequestration capabilities through effective pollution management.


Asunto(s)
Secuestro de Carbono , Nutrientes/análisis , Hydrocharitaceae , Nitrógeno/análisis , Lignina , Fósforo/análisis , Carbono , Biodegradación Ambiental
3.
Chembiochem ; : e202400655, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39303145

RESUMEN

The histamine subtype 3 (H3) receptor is an important drug target in the central nervous system (CNS), and PET imaging offers a promising technique for the noninvasive evaluation of CNS disease related to the H3 receptor. In this study, we synthesized and evaluated the binding effects of [18F]H3-2404 and [18F]H3-2405 by modifying the structure of AZD5213, a selective H3 antagonist. These two radioligands were prepared in high radiochemical yields and displayed stability in serum. The in vitro autoradiographic study in rat brain tissue and the following in vivo PET studies in mice demonstrated sufficient brain uptake but predominantly non-specific distribution in rodent brain. Although these data suggest that [18F]H3-2404 and [18F]H3-2405 are unsuitable as PET tracers for brain imaging of the H3 receptor, this study provides a valuable attempt for optimizing 18F labeled radiotracers based on AZD5213.

4.
Int J Biol Macromol ; 278(Pt 4): 134957, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39182881

RESUMEN

The receptor-binding domain (RBD) is crucial for understanding how severe acute respiratory syndrome coronavirus (SARS-CoV-2) recognizes and infects host cells. Chitooligosaccharide (CS) exhibits diverse antiviral activities, with its derivatives showing remarkable efficacy in blocking SARS-CoV-2 infection. Thus, this study employed spectroscopy, virus-infected cell experiments, and molecular simulation to investigate the molecular interactions between CS and SARS-CoV-2 RBD, as well as their mechanisms. In spectroscopic experiments, all four CS variants with different molecular weights formed interactions with the RBD. These variants increased the resistance of HEK293ACE2 cells to SARS-CoV-2 invasion. Molecular docking revealed that the four CS variants could bind to the RBD through hydrogen bonding or salt-bridge interactions, forming stable complexes. Chitotetraose provided stronger protection to HEK293ACE2 cells compared to other CS variants and displayed higher molecular docking scores. Further investigation into the optimal docking conformation of chitotetraose was conducted through molecular dynamics simulation methods. This study lays a solid theoretical foundation and provides a scientific basis for the development of targeted RBD inhibitors, as well as drug screening and application against novel coronaviruses.


Asunto(s)
Quitosano , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Oligosacáridos , Unión Proteica , SARS-CoV-2 , Humanos , Oligosacáridos/química , Oligosacáridos/farmacología , SARS-CoV-2/efectos de los fármacos , Células HEK293 , Quitosano/química , Quitosano/análogos & derivados , Quitosano/farmacología , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/metabolismo , Glicoproteína de la Espiga del Coronavirus/genética , Antivirales/farmacología , Antivirales/química , COVID-19/virología , Sitios de Unión , Quitina/análogos & derivados , Quitina/química , Quitina/farmacología , Enzima Convertidora de Angiotensina 2/química , Enzima Convertidora de Angiotensina 2/metabolismo , Dominios Proteicos , Tratamiento Farmacológico de COVID-19
5.
Small ; : e2402182, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39161191

RESUMEN

Fe-based 2D materials exhibit rich chemical compositions and structures, which may imply many unique physical properties and promising applications. However, achieving controllable preparation of ultrathin non-layered FeS crystal on SiO2/Si substrate remains a challenge. Herein, the influence of temperature and molecular sieves is reported on the synthesis of ultrathin FeS nanosheets with a thickness as low as 2.3 nm by molecular sieves-assisted chemical vapor deposition (CVD). The grown FeS nanosheets exhibit a non-layered hexagonal NiAs structure and belong to the P63/mmc space group. The inverted symmetry broken structure is confirmed by the angle-resolved second harmonic generation (SHG) test. In particular, the 2D FeS nanosheets exhibit exceptional metallic behavior, with conductivity up to 1.63 × 106 S m-1 at 300 K for an 8 nm thick sample, which is higher than that of reported 2D metallic materials. This work provides a significant contribution to the synthesis and characterization of 2D non-layered Fe-based materials.

6.
J Neurosci ; 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39214706

RESUMEN

Words offer a unique opportunity to separate the processing mechanisms of object subcomponents from those of the whole object, because the phonological or semantic information provided by the word subcomponents (i.e., sublexical information) can conflict with that provided by the whole word (i.e., lexical information). Previous studies have revealed some of the specific brain regions and temporal information involved in sublexical information processing. However, a comprehensive spatiotemporal neural network for sublexical processing remains to be fully elucidated due to the low temporal or spatial resolutions of previous neuroimaging studies. In this study, we recorded stereoelectroencephalography (SEEG) signals with high spatial and temporal resolutions from a large sample of 39 epilepsy patients (both sexes) during a Chinese character oral reading task. We explored the activated brain regions and their connectivity related to three sublexical effects: phonological regularity (whether the whole character's pronunciation aligns with its phonetic radical), phonological consistency (whether characters with the same phonetic radical share the same pronunciation), and semantic transparency (whether the whole character's meaning aligns with its semantic radical). The results revealed that sublexical effects existed in the inferior frontal gyrus, precentral and postcentral gyri, temporal lobe, and middle occipital gyrus. Additionally, connectivity from the middle occipital gyrus to the postcentral gyrus and from postcentral gyrus to the fusiform gyrus was associated with the sublexical effects. These findings provide valuable insights into the spatiotemporal dynamics of sublexical processing and object recognition in the brain.Significance statement Elucidating the intricate neural mechanisms underlying sublexical processing is crucial for understanding the intricacies of language comprehension and object recognition in the human brain. This study employed intracranial stereoelectroencephalography (SEEG) recordings to investigate the spatiotemporal dynamics of sublexical processing during a Chinese character reading task. We constructed a neural network for sublexical processing and depicted its temporal sequence in different brain regions. Furthermore, we identified the information flow within this network and observed its variation with the reading of characters containing different sublexical information. These findings not only advance our understanding of the cerebral mechanisms governing sublexical processing but also offer insights into the broader framework of object recognition processes.

7.
Chem Commun (Camb) ; 60(73): 9946-9949, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39171691

RESUMEN

The synthetic route presented for acrylate-modified hyaluronic acid (HA-A-BEA) offers a simple and efficient process, reducing reaction time and purification steps while retaining biocompatibility. This study demonstrates the ability of HA-A-BEA to form tunable hydrogels via versatile techniques suitable for biomedical applications.

8.
Nat Cell Biol ; 26(8): 1287-1295, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38951706

RESUMEN

α-Synuclein (α-Syn) aggregation is closely associated with Parkinson's disease neuropathology. Physiologically, α-Syn promotes synaptic vesicle (SV) clustering and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly. However, the underlying structural and molecular mechanisms are uncertain and it is not known whether this function affects the pathological aggregation of α-Syn. Here we show that the juxtamembrane region of vesicle-associated membrane protein 2 (VAMP2)-a component of the SNARE complex that resides on SVs-directly interacts with the carboxy-terminal region of α-Syn through charged residues to regulate α-Syn's function in clustering SVs and promoting SNARE complex assembly by inducing a multi-component condensed phase of SVs, α-Syn and other components. Moreover, VAMP2 binding protects α-Syn against forming aggregation-prone oligomers and fibrils in these condensates. Our results suggest a molecular mechanism that maintains α-Syn's function and prevents its pathological amyloid aggregation, the failure of which may lead to Parkinson's disease.


Asunto(s)
Vesículas Sinápticas , Proteína 2 de Membrana Asociada a Vesículas , alfa-Sinucleína , alfa-Sinucleína/metabolismo , alfa-Sinucleína/genética , Proteína 2 de Membrana Asociada a Vesículas/metabolismo , Proteína 2 de Membrana Asociada a Vesículas/genética , Vesículas Sinápticas/metabolismo , Animales , Humanos , Unión Proteica , Proteínas SNARE/metabolismo , Proteínas SNARE/genética , Ratones , Ratas , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/patología , Neuronas/metabolismo , Neuronas/patología , Chaperonas Moleculares/metabolismo , Chaperonas Moleculares/genética
9.
Sci Total Environ ; 946: 174396, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-38950634

RESUMEN

Salt marsh has an important 'purification' role in coastal ecosystems by removing excess nitrogen that could otherwise harm aquatic life and reduce water quality. Recent studies suggest that salt marsh root exudates might be the 'control centre' for nitrogen transformation, but empirical evidence is lacking. Here we sought to estimate the direction and magnitude of nitrogen purification by salt marsh root exudates and gain a mechanistic understanding of the biogeochemical transformation pathway(s). To achieve this, we used a laboratory incubation to quantify both the root exudates and soil nitrogen purification rates, in addition to the enzyme activities and functional genes under Phragmites australis populations with different nitrogen forms addition (NO3-, NH4+ and urea). We found that NO3- and urea addition significantly stimulate P. australis root exudation of total acids, amino acids, total sugars and total organic carbon, while NH4+ addition only significantly increased total acids, amino acids and total phenol exudation. High total sugars, amino acids and total organic carbon concentrations enlarged nitrogen purification potential by stimulating the nitrogen purifying bacterial activities (including enzyme activities and related genes expression). Potential denitrification rates were not significantly elevated under NH4+ addition in comparison to NO3- and urea addition, which should be ascribed to total phenol self-toxicity and selective inhibition. Further, urea addition stimulated urease and protease activities with providing more NH4+ and NO2- substrates for elevated anaerobic ammonium oxidation rates among the nitrogen addition treatments. Overall, this study revealed that exogenous nitrogen could increase the nitrogen purification-associated bacterial activity through accelerating the root exudate release, which could stimulate the activity of nitrogen transformation, and then improve the nitrogen removal capacity in salt marsh.


Asunto(s)
Nitrógeno , Raíces de Plantas , Suelo , Humedales , Nitrógeno/metabolismo , Raíces de Plantas/metabolismo , Suelo/química , Poaceae , Exudados de Plantas , Desnitrificación
10.
Int J Biol Macromol ; 276(Pt 2): 133988, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39032887

RESUMEN

Ultraviolet B (UVB) radiation accelerates the aging process of skin cells by triggering oxidative stress and inflammatory responses. The aim of this study was to investigate the mechanism of action of sRNAs and protein molecules in the regenerative extracellular vesicles of Lactobacillus plantarum against the UVB-induced photoaging process of human keratinocytes. The extracellular vesicles regenerated by Lactobacillus plantarum were isolated and purified to identify sRNAs and protein components. Human keratinocytes were treated with UVB radiation to simulate the photoaging model. The effects of different concentrations of vesicle extract on cell survival rate, oxidative stress index and inflammatory marker expression were evaluated in control group and treatment group. The results showed that the regenerated extracellular vesicles of L. plantarum significantly improved the survival rate of keratinocytes after UVB radiation, and delayed the aging process of skin cells by reducing oxidative stress and inhibiting inflammatory response.


Asunto(s)
Vesículas Extracelulares , Queratinocitos , Lactobacillus plantarum , Envejecimiento de la Piel , Rayos Ultravioleta , Lactobacillus plantarum/química , Humanos , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Queratinocitos/efectos de la radiación , Vesículas Extracelulares/metabolismo , Envejecimiento de la Piel/efectos de los fármacos , Envejecimiento de la Piel/efectos de la radiación , Estrés Oxidativo/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , ARN Pequeño no Traducido
11.
Natl Sci Rev ; 11(6): nwae182, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38962715

RESUMEN

Accumulation of aggregated α-synuclein (α-syn) in Lewy bodies is the pathological hallmark of Parkinson's disease (PD). Genetic mutations in lipid metabolism are causative for a subset of patients with Parkinsonism. The role of α-syn's lipid interactions in its function and aggregation is recognized, yet the specific lipids involved and how lipid metabolism issues trigger α-syn aggregation and neurodegeneration remain unclear. Here, we found that α-syn shows a preference for binding to lysophospholipids (LPLs), particularly targeting lysophosphatidylcholine (LPC) without relying on electrostatic interactions. LPC is capable of maintaining α-syn in a compact conformation, significantly reducing its propensity to aggregate both in vitro and within cellular environments. Conversely, a reduction in the production of cellular LPLs is associated with an increase in α-syn accumulation. Our work underscores the critical role of LPLs in preserving the natural conformation of α-syn to inhibit improper aggregation, and establishes a potential connection between lipid metabolic dysfunction and α-syn aggregation in PD.

12.
Inorg Chem ; 63(26): 12316-12322, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38885131

RESUMEN

Blue-emitting colloidal CsPbX3 (X = Br, Cl, or I) perovskite nanocrystals have emerged as one of the most fascinating materials for optoelectronic applications. However, their applicability is hindered by poor stability and a low photoluminescence efficiency. Herein, highly stable CsPbBr3 nanoplatelets exhibiting intense blue luminescence are fabricated by employing a strategy in which the morphology is regulated and the surface is subjected to dual passivation through the incorporation of zirconium acetylacetonate [Zr(acac)4]. The passivated CsPbBr3 nanocrystals exhibit adjustable light emission from green to dark blue and a controllable morphology from nanocubes (NCs) to nanoplatelets (NPLs) and nanorods accomplished by varying the content of Zr(acac)4. The optimized NPLs are characterized by a bright blue emission with a central wavelength of 459 nm and a high photoluminescence quantum yield of 90%. The addition of Zr(acac)4 in the synthesis of CsPbBr3 induces oriented growth with a two-dimensional morphology. The Zr(acac)4 can repair the surface defects of the nanocrystal surface, and the surface is also capped with the Zr(OH)4 cluster layer. Therefore, the passivated blue-emitting NPLs exhibit outstanding stability compared to that of pristine NPLs during long-term storage and exposure to light. This work provides a novel strategy for fabricating highly stable PNCs with deep-blue emission and widens their potential applications in blue-emitting optoelectronic devices.

13.
Mar Environ Res ; 198: 106549, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38733739

RESUMEN

Alternative splicing (AS) is an important post-transcriptional mechanism for adaptation of fish to environmental stress. Here, we performed a genome-wide investigation to AS dynamics in greater amberjack (Seriola dumerili), an economical marine teleost, in response to hypo- (10 ppt) and hyper-salinity (40 ppt) stresses. Totally, 2267-2611 differentially spliced events were identified in gills and kidney upon the exposure to undesired salinity regimes. In gills, genes involved in energy metabolism, stimulus response and epithelial cell differentiation were differentially spliced in response to salinity variation, while sodium ion transport and cellular amide metabolism were enhanced in kidney to combat the adverse impacts of salinity changes. Most of these differentially spliced genes were not differentially expressed, and AS was found to regulate different biological processes from differential gene expression, indicative of the functionally nonredundant role of AS in modulating salinity acclimation in greater amberjack. Together, our study highlights the important contribution of post-transcriptional mechanisms to the adaptation of fish to ambient salinity fluctuations and provides theoretical guidance for the conservation of marine fishery resources against increasingly environmental challenges.


Asunto(s)
Aclimatación , Empalme Alternativo , Salinidad , Animales , Aclimatación/genética , Branquias/metabolismo , Peces/genética , Peces/fisiología
14.
Traffic Inj Prev ; 25(6): 860-869, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38717825

RESUMEN

OBJECTIVE: Mountain highways are linearly complex, with extensive curves and high accident injury rates, how to improve driving safety is the key to traffic safety management on mountain highways, and it also meets the need for harmonious and sustainable development of the society. Therefore, this study investigates the effects of different guardrail color configurations on the driving behavior of different styles of drivers when driving on mountainous curves from the perspective of improving road aids - guardrails. METHODS: A virtual reality experiment was designed using a driving simulator and VR technology, and 64 subjects were recruited to participate and complete the experiment. RESULTS: Drivers with non-adaptive driving styles (Reckless, Angry, Anxious) traveled at significantly higher speeds than subjects with adaptive driving styles (Cautious) on mountainous roads; drivers with Cautious styles had better lane-keeping ability when passing through different radii of curves as compared to non-adaptive drivers; and the red and yellow guardrails were more effective in decreasing the speeds at which drivers passed and in increasing the stability of lane-keeping. CONCLUSIONS: The results of the study show that the effectiveness of red and yellow guardrails is better, which provides a reference for the traffic management department to propose a standardized color setting of guardrails in mountainous areas, which is conducive to the development of more precise traffic management measures to reduce the occurrence of traffic accidents.


Asunto(s)
Conducción de Automóvil , Color , Realidad Virtual , Humanos , Conducción de Automóvil/psicología , Masculino , Femenino , Adulto Joven , Adulto , Accidentes de Tránsito/prevención & control , Simulación por Computador , Equipos de Seguridad
15.
J Cardiothorac Surg ; 19(1): 265, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38664788

RESUMEN

BACKGROUND: Hypoxia/reoxygenation (H/R) induces cardiomyocyte ferroptosis, a core remodeling event in myocardial ischemia/reperfusion injury. Methyltransferase-like 14 (METTL14) emerges as a writer of N6-methyladenosine (m6A) modification. This study was conducted to decipher the role of METTL14 in H/R-induced cardiomyocyte ferroptosis. METHODS: Mouse cardiomyocytes HL-1 were cultured and underwent H/R treatment. The degree of ferroptosis after H/R treatment was appraised by the cell counting kit-8 assay, assay kits (ROS/GSH/Fe2+), and Western blotting (GPX4/ACSL4). The intracellular expressions of METTL14, pri-miR-146a-5p, miR-146a-5p, or adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1) were examined by real-time quantitative polymerase chain reaction or Western blotting, with m6A quantification analysis and RNA immunoprecipitation to determine the total m6A level and the expression of pri-miR-146a-5p bound to DiGeorge critical region 8 (DGCR8) and m6A-modified pri-miR-146a-5p. The binding of miR-146a-5p to APPL1 was testified by the dual-luciferase assay. RESULTS: H/R treatment induced cardiomyocyte ferroptosis (increased ROS, Fe2+, and ACSL4 and decreased GSH and GPX4) and upregulated METTL14 expression. METTL14 knockdown attenuated H/R-induced cardiomyocyte ferroptosis. METTL14 induced the recognition of pri-miR-146a-5p by DGCR8 by increasing m6A modification on pri-miR-146a-5p, which promoted the conversion of pri-miR-146a-5p into miR-146a-5p and further repressed APPL1 transcription. miR-146a-5p upregulation or APPL1 downregulation limited the inhibitory effect of METTL14 downregulation on H/R-induced cardiomyocyte ferroptosis. CONCLUSION: METTL14 promoted miR-146a-5p expression through the recognition and processing of pri-miR-146a-5p by DGCR8, which repressed APPL1 transcription and triggered H/R-induced cardiomyocyte ferroptosis.


Asunto(s)
Adenosina , Adenosina/análogos & derivados , Ferroptosis , Metiltransferasas , Daño por Reperfusión Miocárdica , Miocitos Cardíacos , Ferroptosis/fisiología , Ferroptosis/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Animales , Adenosina/metabolismo , Ratones , Metiltransferasas/metabolismo , Metiltransferasas/genética , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/genética , MicroARNs/genética , MicroARNs/metabolismo
16.
bioRxiv ; 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-38496494

RESUMEN

Post-translational modifications (PTMs) of α-synuclein (α-syn) such as acetylation and phosphorylation play important yet distinct roles in regulating α-syn conformation, membrane binding, and amyloid aggregation. However, how PTMs regulate α-syn function in presynaptic terminals remains unclear. Previously, we reported that α-syn clusters synaptic vesicles (SV) 1 , and neutral phospholipid lysophosphatidylcholine (LPC) can mediate this clustering 2 . Here, based on our previous findings, we further demonstrate that N-terminal acetylation, which occurs under physiological conditions and is irreversible in mammalian cells, significantly enhances the functional activity of α-syn in clustering SVs. Mechanistic studies reveal that this enhancement is caused by the N-acetylation-promoted insertion of α-syn's N-terminus and increased intermolecular interactions on the LPC-containing membrane. Our work demonstrates that N-acetylation fine-tunes α-syn-LPC interaction for mediating α-syn's function in SV clustering.

17.
Small ; 20(33): e2401379, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38522026

RESUMEN

Phase transitions of Mn-based cathode materials associated with the charge and discharge process play a crucial role on the rate capability and cycle life of zinc ion batteries. Herein, a microscopic electrochemical failure mechanism of Zn-MnO2 batteries during the phase transitions from δ-MnO2 to λ-ZnMn2O4 is presented via systematic first-principle investigation. The initial insertion of Zn2+ intensifies the rearrangement of Mn. This is completed by the electrostatic repulsion and co-migration between guest and host ions, leading to the formation of λ-ZnMn2O4. The Mn relocation barrier for the λ-ZnMn2O4 formation path with 1.09 eV is significantly lower than the δ-MnO2 re-formation path with 2.14 eV, indicating the irreversibility of the layered-to-spinel transition. Together with the phase transition, the rearrangement of Mn elevates the Zn2+ migration barrier from 0.31 to 2.28 eV, resulting in poor rate performance. With the increase of charge-discharge cycles, irreversible and inactive λ-ZnMn2O4 products accumulate on the electrode, causing continuous capacity decay of the Zn-MnO2 battery.

18.
Microvasc Res ; 154: 104681, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38493885

RESUMEN

BACKGROUND: Arterial baroreflex dysfunction, like many other central nervous system disorders, involves disruption of the blood-brain barrier, but what causes such disruption in ABR dysfunction is unclear. Here we explored the potential role of platelets in this disruption. METHODS: ABR dysfunction was induced in rats using sinoaortic denervation, and the effects on integrity of the blood-brain barrier were explored based on leakage of Evans blue or FITC-dextran, while the effects on expression of CD40L in platelets and of key proteins in microvascular endothelial cells were explored using immunohistochemistry, western blotting and enzyme-linked immunosorbent assay. Similar experiments were carried out in rat brain microvascular endothelial cell line, which we exposed to platelets taken from rats with ABR dysfunction. RESULTS: Sinoaortic denervation permeabilized the blood-brain barrier and downregulated zonula occludens-1 and occludin in rat brain, while upregulating expression of CD40L on the surface of platelets and stimulating platelet aggregation. Similar effects of permeabilization and downregulation were observed in healthy rats that received platelets from animals with ABR dysfunction, and in rat brain microvascular endothelial cells, but only in the presence of lipopolysaccharide. These effects were associated with activation of NF-κB signaling and upregulation of matrix metalloprotease-9. These effects of platelets from animals with ABR dysfunction were partially blocked by neutralizing antibody against CD40L or the platelet inhibitor clopidogrel. CONCLUSION: During ABR dysfunction, platelets may disrupt the blood-brain barrier when CD40L on their surface activates NF-kB signaling within cerebral microvascular endothelial cells, leading to upregulation of matrix metalloprotease-9. Our findings imply that targeting CD40L may be effective against cerebral diseases involving ABR dysfunction.


Asunto(s)
Barorreflejo , Plaquetas , Barrera Hematoencefálica , Ligando de CD40 , Permeabilidad Capilar , Modelos Animales de Enfermedad , Células Endoteliales , Metaloproteinasa 9 de la Matriz , FN-kappa B , Ratas Sprague-Dawley , Transducción de Señal , Animales , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/fisiopatología , Barrera Hematoencefálica/patología , Plaquetas/metabolismo , Masculino , Células Endoteliales/metabolismo , Ligando de CD40/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , FN-kappa B/metabolismo , Proteína de la Zonula Occludens-1/metabolismo , Ocludina/metabolismo , Línea Celular , Agregación Plaquetaria , Presión Arterial , Ratas
19.
Biomacromolecules ; 25(4): 2645-2655, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38456398

RESUMEN

Conventional techniques for the closure of wounds, such as sutures and staples, have significant drawbacks that can negatively impact wound healing. Tissue adhesives have emerged as promising alternatives, but poor adhesion, low mechanical properties, and toxicity have hindered their widespread clinical adoption. In this work, a dual modified, aldehyde and methacrylate hyaluronic acid (HA) biopolymer (HA-MA-CHO) has been synthesized through a simplified route for use as a double cross-linked network (DCN) hydrogel (HA-MA-CHO-DCN) adhesive for the effective closure and sealing of wounds. HA-MA-CHO-DCN cross-links in two stages: initial cross-linking of the aldehyde functionality (CHO) of HA-MA-CHO using a disulfide-containing cross-linker, 3,3'-dithiobis (propionic hydrazide) (DTPH), leading to the formation of a self-healing injectable gel, followed by further cross-linking via ultraviolet (UV) initiated polymerization of the methacrylate (MA) functionality. This hydrogel adhesive shows a stable swelling behavior and remarkable versatility as the storage modulus (G') has shown to be highly tunable (103-105 Pa) for application to many different wound environments. The new HA-MA-CHO-DCN hydrogel showed excellent adhesive properties by surpassing the burst pressure and lap-shear strength for the widely used bovine serum albumin-glutaraldehyde (BSAG) glue while maintaining excellent cell viability.


Asunto(s)
Ácido Hialurónico , Hidrogeles , Hidrogeles/química , Ácido Hialurónico/química , Adhesivos , Glutaral , Metacrilatos
20.
ACS Appl Mater Interfaces ; 16(14): 17637-17648, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38549247

RESUMEN

Aqueous zinc-ion batteries (ZIBs) are competitive among the elective candidates for electrochemical energy storage systems, but the intrinsic drawbacks of zinc metal anodes such as dendrites and corrosion severely hinder their large-scale application. Developing alternative anode materials capable of high reversibility and stability for storing Zn2+ ions is a feasible approach to circumvent the challenge. Herein, a sulfur-defect-induced TiS1.94 (D-TiS1.94) as a promising intercalation anode material for ZIBs is designed. The abundant Zn2+-storage active sites and lower Zn2+ migration barrier induced by sulfur defects endow D-TiS1.94 with a high capacity for Zn2+-storage (219.1 mA h g-1 at 0.05 A g-1) and outstanding rate capability (107.3 mA h g-1 at 5 A g-1). In addition, a slight volume change of 8.1% is identified upon Zn2+ storage, which favors a prolonged cycling life (50.3% capacity remaining in 1500 cycles). More significantly, the D-TiS1.94||ZnxMnO2 full battery demonstrates a high discharge capacity of 155.7 mA h g-1 with a capacity retention of 59.8% in 400 cycles. It has been estimated that the high-capacity, low-operation voltage, and long-life D-TiS1.94 can be a promising component of the ZIB anode material family, and the strategy proposed in this work will provide guidance to the defect engineering of high-performance electrode materials toward energy storage applications.

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