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1.
Adv Mater ; : e2314063, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38444248

RESUMO

Polymer/ceramic-based composite solid electrolytes (CSE) are promising candidates for all-solid-state lithium metal batteries (SLBs), benefiting from the combined mechanical robustness of polymeric electrolytes and the high ionic conductivity of ceramic electrolytes. However, the interfacial instability and poorly understood interphases of CSE hinder their application in high-voltage SLBs. Herein, a simple but effective CSE that stabilizes high-voltage SLBs by forming multiple intermolecular coordination interactions between polyester and ceramic electrolytes is discovered. The multiple coordination between the carbonyl groups in poly(ε-caprolactone) and the fluorosulfonyl groups in anions with Li6.5 La3 Zr1.5 Ta0.5 O12 nanoparticles is directly visualized by cryogenic transmission electron microscopy and further confirmed by theoretical calculation. Importantly, the multiple coordination in CSE not only prevents the continuous decomposition of polymer skeleton by shielding the vulnerable carbonyl sites but also establishes stable inorganic-rich interphases through preferential decomposition of anions. The stable CSE and its inorganic-rich interphases enable Li||Li symmetric cells with an exceptional lifespan of over 4800 h without dendritic shorting at 0.1 mA cm-2 . Moreover, the high-voltage SLB with LiNi0.5 Co0.2 Mn0.3 O2 cathode displays excellent cycling stability over 1100 cycles at a 1C charge/discharge rate. This work reveals the underlying mechanism behind the excellent stability of coordinating composite electrolytes and interfaces in high-voltage SLBs.

2.
J Cell Physiol ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38477420

RESUMO

Parkinson's disease (PD) is the most prevalent neurodegenerative disorder. Neuroinflammation mediated by activated microglia and apoptosis of dopaminergic (DA) neurons in the midbrain are its primary pathological manifestations. Leucine-rich repeat protein kinase 2 (LRRK2) kinase has been observed to increase expression during neuroinflammation, however, the effect of LRRK2 on microglia activation remains poorly understood. In this study, we have established lipopolysaccharide (LPS) treated BV2 cells and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models for both in vivo and in vitro investigation. Our data in vivo reveal that LRRK2 can promote microglia activation by regulating ferroptosis and activating nuclear factor-κB. Inhibition of LRRK2 expression effectively suppressed the LPS-induced pro-inflammatory cytokines and facilitated the secretion of neuroprotective factors. Importantly, by co-overexpressing LRRK2 and glutathione peroxidase 4 (GPX4), we identified the system Xc-GSH-GPX4 pathway as a crucial component in LRRK2-mediated microglial ferroptosis and inflammatory responses. Using a microglial culture supernatant (MCS) transfer model, we found that inhibiting LRRK2 or downregulating ferroptosis in BV2 cells prevented SH-SY5Y cell apoptosis. Additionally, we observed abundant expression of LRRK2 and P-P65 in the midbrain, which was elevated in the MPTP-induced PD model, along with microglia activation. LRRK2 and P-P65 expression inhibition with PF-06447475 attenuated microglia activation in the nigrostriatal dense part of MPTP-treated mice. Based on our findings, it is evident that LRRK2 plays a critical role in promoting the neuroinflammatory response during the pathogenesis of PD by regulating the system Xc-GSH-GPX4 pathway. Taken together, our data highlights the potential research and therapeutic value of targeting LRRK2 to regulate neuroinflammatory response in PD through ferroptosis.

3.
Nature ; 628(8006): 84-92, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38538792

RESUMO

Wearable electronics with great breathability enable a comfortable wearing experience and facilitate continuous biosignal monitoring over extended periods1-3. However, current research on permeable electronics is predominantly at the stage of electrode and substrate development, which is far behind practical applications with comprehensive integration with diverse electronic components (for example, circuitry, electronics, encapsulation)4-8. Achieving permeability and multifunctionality in a singular, integrated wearable electronic system remains a formidable challenge. Here we present a general strategy for integrated moisture-permeable wearable electronics based on three-dimensional liquid diode (3D LD) configurations. By constructing spatially heterogeneous wettability, the 3D LD unidirectionally self-pumps the sweat from the skin to the outlet at a maximum flow rate of 11.6 ml cm-2 min-1, 4,000 times greater than the physiological sweat rate during exercise, presenting exceptional skin-friendliness, user comfort and stable signal-reading behaviour even under sweating conditions. A detachable design incorporating a replaceable vapour/sweat-discharging substrate enables the reuse of soft circuitry/electronics, increasing its sustainability and cost-effectiveness. We demonstrated this fundamental technology in both advanced skin-integrated electronics and textile-integrated electronics, highlighting its potential for scalable, user-friendly wearable devices.


Assuntos
Eletrônica , Dispositivos Eletrônicos Vestíveis , Pele , Têxteis , Eletrodos
4.
Adv Mater ; : e2400041, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38469733

RESUMO

The acquisition of stable and high-areal-capacity S cathodes over 10 mA h cm-2 is a critical and indispensable step to realize the high energy density configuration. However, increasing the areal capacity of S cathodes often deteriorates the specific capacity and stability due to the aggravated dissolution of S and diffusion of solvable polysulfides in the thick electrode. Herein, the design of a freestanding composite cathode that leverages 3D covalent binding sites and chemical adsorption environment to offer dissolution-limiting and diffusion-blocking functions of S species is reported. By employing this architecture, the coin cell exhibits excellent cycling stability and an exceptional specific capacity of 1444.3 mA h g-1 (13 mA h cm-2 ), and the pouch cell configuration manifests a noteworthy areal capacity exceeding 11 mA h cm-2 . This performance is coupled with excellent flexibility, demonstrated through consecutive bending cycle tests, even at a sulfur loading of 9.00 mg cm-2 . This study lays the foundation for the development of flexible Li-S batteries with increased loading capacities and exceptional performance.

5.
Chem Rev ; 124(4): 1535-1648, 2024 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-38373392

RESUMO

Over the years, researchers have made significant strides in the development of novel flexible/stretchable and conductive materials, enabling the creation of cutting-edge electronic devices for wearable applications. Among these, porous conductive textiles (PCTs) have emerged as an ideal material platform for wearable electronics, owing to their light weight, flexibility, permeability, and wearing comfort. This Review aims to present a comprehensive overview of the progress and state of the art of utilizing PCTs for the design and fabrication of a wide variety of wearable electronic devices and their integrated wearable systems. To begin with, we elucidate how PCTs revolutionize the form factors of wearable electronics. We then discuss the preparation strategies of PCTs, in terms of the raw materials, fabrication processes, and key properties. Afterward, we provide detailed illustrations of how PCTs are used as basic building blocks to design and fabricate a wide variety of intrinsically flexible or stretchable devices, including sensors, actuators, therapeutic devices, energy-harvesting and storage devices, and displays. We further describe the techniques and strategies for wearable electronic systems either by hybridizing conventional off-the-shelf rigid electronic components with PCTs or by integrating multiple fibrous devices made of PCTs. Subsequently, we highlight some important wearable application scenarios in healthcare, sports and training, converging technologies, and professional specialists. At the end of the Review, we discuss the challenges and perspectives on future research directions and give overall conclusions. As the demand for more personalized and interconnected devices continues to grow, PCT-based wearables hold immense potential to redefine the landscape of wearable technology and reshape the way we live, work, and play.


Assuntos
Eletrônica , Dispositivos Eletrônicos Vestíveis , Porosidade , Têxteis , Condutividade Elétrica
6.
Heliyon ; 10(4): e26303, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38379975

RESUMO

Background: Bilateral deep thalamic nucleus brain stimulation (STN-DBS) surgery is often used to treat the motor symptoms of patients with Parkinson's disease. The change of neurocognitive symptoms in patients is, however, still unclear. Objective: We aimed at analyzing the deterioration of neurocognitive symptoms in patients with Parkinson's disease after deep brain stimulation surgery under different follow-up times. Methods: A comprehensive literature review was conducted using Pubmed, Cochrane Library, and Web of Science to screen eligible study records, the meta-analysis was performed using an inverse variance method and a random-effects model. Additionally, the areas of analysis include five: cognition, executive function, memory capacity, and verbal fluency (phonetic fluency and semantic fluency). They were analyzed for changes at six and twelve months postoperatively compared to baseline. The Meta-analysis has been registered with PROSPERO under the registration number: CRD42022308786. Results: In terms of overall cognitive performance, executive function, and memory capacity, the original studies show a trend of improvement in these areas at 12 months postoperatively compared with 6 months, at variance, patients did not improve or deteriorated in phonetic fluency(d = -0.42 at both 6-month and 12-month follow-up) and semantic fluency from 6 to 12 months postoperatively. Conclusion: In terms of most neurocognitive symptoms, including cognitive ability, executive function, and learning memory capacity, bilateral STN-DBS surgery appears to be safe at relatively long follow-up times. However, postoperative phonetic and semantic fluency changes should still not be underestimated, and clinicians should pay more attention to patients' changes in both.

7.
Nat Commun ; 15(1): 887, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38291087

RESUMO

Textile-based wearable electronics have attracted intensive research interest due to their excellent flexibility and breathability inherent in the unique three-dimensional porous structures. However, one of the challenges lies in achieving highly conductive patterns with high precision and robustness without sacrificing the wearing comfort. Herein, we developed a universal and robust in-textile photolithography strategy for precise and uniform metal patterning on porous textile architectures. The as-fabricated metal patterns realized a high precision of sub-100 µm with desirable mechanical stability, washability, and permeability. Moreover, such controllable coating permeated inside the textile scaffold contributes to the significant performance enhancement of miniaturized devices and electronics integration through both sides of the textiles. As a proof-of-concept, a fully integrated in-textiles system for multiplexed sweat sensing was demonstrated. The proposed method opens up new possibilities for constructing multifunctional textile-based flexible electronics with reliable performance and wearing comfort.

8.
Adv Sci (Weinh) ; 11(6): e2307726, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38072644

RESUMO

Solid-state lithium metal batteries (SSLMBs) offer numerous advantages in terms of safety and theoretical specific energy density. However, their main components namely lithium metal anode, solid-state electrolyte, and cathode, show chemical instability when exposed to humid air, which results in low capacities and poor cycling stability. Recent studies have shown that bioinspired hydrophobic materials with low specific surface energies can protect battery components from corrosion caused by humid air. Air-stable inorganic materials that densely cover the surface of battery components can also provide protection, which improves the storage stability of the battery components, broadens their processing conditions, and ultimately decreases their processing costs while enhancing their safety. In this review, the mechanism behind the surface structural degradation of battery components and the resulting consequences are discussed. Subsequently, recent strategies are reviewed to address this issue from the perspectives of lithium metal anodes, solid-state electrolytes, and cathodes. Finally, a brief conclusion is provided on the current strategies and fabrication suggestions for future safe air-stable SSLMBs.

9.
Macromol Biosci ; 24(2): e2300302, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37815522

RESUMO

Cardiovascular diseases (CVDs) have become the leading global burden of diseases in recent years and are the primary cause of human mortality and loss of healthy life expectancy. Myocardial infarction (MI) is the top cause of CVDs-related deaths, and its incidence is increasing worldwide every year. Recently, hydrogels have garnered great interest from researchers as a promising therapeutic option for cardiac tissue repair after MI. This is due to their excellent properties, including biocompatibility, mechanical properties, injectable properties, anti-inflammatory properties, antioxidant properties, angiogenic properties, and conductive properties. This review discusses the advantages of hydrogels as a novel treatment for cardiac tissue repair after MI. The design strategies of various hydrogels in MI treatment are then summarized, and the latest research progress in the field is classified. Finally, the future perspectives of this booming field are also discussed at the end of this review.


Assuntos
Hidrogéis , Infarto do Miocárdio , Humanos , Hidrogéis/uso terapêutico , Infarto do Miocárdio/terapia
10.
Adv Mater ; 36(13): e2311633, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38112378

RESUMO

Moisture and thermal comfort are critical for long-term wear. In recent years, there has been rapidly growing attention on the importance of the comfortability in wearable electronic textiles (e-textiles), particularly in fields such as health monitoring, sports training, medical diagnosis and treatment, where long-term comfort is crucial. Nonetheless, simultaneously regulating thermal and moisture comfort for the human body without compromising electronic performance remains a significant challenge to date. Herein, a thermal and moisture managing e-textile (TMME-textile) that integrates unidirectional water transport and daytime radiative cooling properties with highly sensitive sensing performance is developed. The TMME-textile is made by patterning sensing electrodes on rationally designed Janus hierarchical gradient honeycombs that offer wetting gradient and optical management. The TMME-textile can unidirectionally pump excessive sweat, providing a dry and comfortable microenvironment for users. Moreover, it possesses high solar reflectivity (98.3%) and mid-infrared emissivity (89.2%), which reduce skin temperature by ≈7.0 °C under a solar intensity of 1 kW m-2. The TMME-textile-based strain sensor displays high sensitivity (0.1749 kPa-1) and rapid response rate (170 ms), effectively enabling smooth long-term monitoring, especially during high-intensity outdoor sports where thermal and moisture stresses are prominent challenges to conventional e-textiles.


Assuntos
Temperatura Baixa , Temperatura Cutânea , Humanos , Luz Solar , Têxteis , Molhabilidade
11.
Sci Adv ; 9(45): eadj2763, 2023 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-37948514

RESUMO

Textile bioelectronics that allow comfortable epidermal contact hold great promise in noninvasive biosensing. However, their applications are limited mainly because of the large intrinsic electrical resistance and low compatibility for electronics integration. We report an integrated wristband that consists of multifunctional modules in a single piece of textile to realize wireless epidermal biosensing. The in-textile metallic patterning and reliable interconnect encapsulation contribute to the excellent electrical conductivity, mechanical robustness, and waterproofness that are competitive with conventional flexible devices. Moreover, the well-maintained porous textile architectures deliver air permeability of 79 mm s-1 and moisture permeability of 270 g m-2 day-1, which are more than one order of magnitude higher than medical tapes, thus ensuring superior wearing comfort. The integrated in-textile wristband performed continuous sweat potassium monitoring in the range of 0.3 to 40 mM with long-term stability, demonstrating its great potential for wearable fitness monitoring and point-of-care testing.


Assuntos
Técnicas Biossensoriais , Dispositivos Eletrônicos Vestíveis , Epiderme , Suor , Têxteis
12.
Artigo em Inglês | MEDLINE | ID: mdl-37874909

RESUMO

Flexible copper conductors have been extensively utilized in flexible and wearable electronics. They can be fabricated by using a variety of patterning techniques such as vacuum deposition, photolithography, and various printing techniques. However, vacuum deposition and photolithography are costly and result in material wastage. Moreover, traditional printing inks require posttreatment, which can damage flexible substrates, or grafting polymers, which involve complex processes to adhere to flexible substrates. Therefore, this study proposes a facile method of fabricating flexible metal patterns with high electrical conductivities and remarkable bonding forces on a diverse range of flexible substrates. Catalytic ink was prepared by using a mixture of epoxy resin, copper nanopowder, and nanosilica. The ink was applied to a variety of flexible substrates, including a poly(ethylene terephthalate) (PET) film, polyimide film, and filter paper, using screen printing to establish a bridge layer for subsequent electroless deposition (ELD). The catalytic efficiency was significantly improved by treating the cured ink patterns with air plasma. The fabricated flexible metals exhibited excellent adhesion and desirable electrical conductivity. The sheet resistance of the copper layer on the PET substrate decreased to 9.2 mΩ/□ after 150 min of ELD. The resistance of the flexible metal on the PET substrate increased by only 3.125% after 5000 bending cycles. The flexible metals prepared in this study demonstrated good foldability, and the samples with filter paper and PET substrates failed after 40 and 70 folds, respectively. A pressure sensor with a bottom electrode consisting of a copper interdigital electrode on a PET substrate displayed favorable sensing performance.

13.
Adv Sci (Weinh) ; 10(30): e2303711, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37672887

RESUMO

The gene mutations of LRRK2, which encodes leucine-rich repeat kinase 2 (LRRK2), are associated with one of the most prevalent monogenic forms of Parkinson's disease (PD). However, the potential effectors of the Gly2019Ser (G2019S) mutation remain unknown. In this study, the authors investigate the effects of LRRK2 G2019S on endoplasmic reticulum (ER) stress in induced pluripotent stem cell (iPSC)-induced dopamine neurons and explore potential therapeutic targets in mice model. These findings demonstrate that LRRK2 G2019S significantly promotes ER stress in neurons and mice. Interestingly, inhibiting LRRK2 activity can ameliorate ER stress induced by the mutation. Moreover, LRRK2 mutation can induce ER stress by directly interacting with thrombospondin-1/transforming growth factor beta1 (THBS1/TGF-ß1). Inhibition of LRRK2 kinase activity can effectively suppress ER stress and the expression of THBS1/TGF-ß1. Knocking down THBS1 can rescue ER stress by interacting with TGF-ß1 and behavior burden caused by the LRRK2 mutation, while suppression of TGF-ß1 has a similar effect. Overall, it is demonstrated that the LRRK2 mutation promotes ER stress by directly interacting with THBS1/TGF-ß1, leading to neural death in PD. These findings provide valuable insights into the pathogenesis of PD, highlighting potential diagnostic markers and therapeutic targets.


Assuntos
Doença de Parkinson , Animais , Camundongos , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo , Mutação/genética , Doença de Parkinson/genética , Fator de Crescimento Transformador beta1/genética
14.
ACS Appl Mater Interfaces ; 15(37): 44342-44353, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37668314

RESUMO

As a flexible artificial material, the conductive hydrogel has broad application prospects in flexible wearable electronics, soft robotics, and biomedical monitoring. However, traditional hydrogels still face many challenges, such as long-term stability, availability in extreme environments, and long-lasting adhesion to the skin surface under sweaty or humid conditions. To circumvent the above issues, one kind of ionic conductive hydrogel was prepared by a simple one-pot method that dissolved chitosan (CS), 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS), tannic acid (TA), and 2-methoxy-ethyl acrylate (MEA) into dimethyl sulfoxide (DMSO)/H2O solvent. The resulting hydrogel showed excellent tensile properties (1440%), extreme environmental tolerance (-40-60 °C), adhesion (72 KPa at porcine skin), ionic conductivity (0.87 S m-1), and high-efficiency antibacterial property. Furthermore, the produced organohydrogel strain sensor exhibited high strain sensitivity (GF = 4.07), excellent signal sensing capabilities (human joint movement, microexpression, and sound signals), and long-term cyclic stability (400 cycles). Looking beyond, this work provides a simple and promising strategy for using hydrogel sensors in extreme environments for e-skin, health monitoring, and wearable electronic devices.


Assuntos
Antibacterianos , Quitosana , Humanos , Suínos , Animais , Dimetil Sulfóxido , Condutividade Elétrica , Hidrogéis
15.
Small Methods ; 7(11): e2300671, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37661591

RESUMO

Stretchable electronics possess significant advantages over their conventional rigid counterparts and boost game-changing applications such as bioelectronics, flexible displays, wearable health monitors, etc. It is, nevertheless, a formidable task to impart stretchability to brittle electronic materials such as silicon. This review provides a concise but critical discussion of the prevailing structural engineering strategies for achieving strain-tolerant electronic devices. Not only the more commonly discussed lateral designs of structures such as island-bridge, wavy structures, fractals, and kirigami, but also the less discussed vertical architectures such as strain isolation and elastoplastic principle are reviewed. Future opportunities are envisaged at the end of the paper.

16.
Small ; 19(50): e2304353, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37620125

RESUMO

Fiber-shaped conductors with high electrical conductivity, stretchability, and durability have attracted increasing attention due to their potential for integration into arbitrary wearable forms. However, these fiber conductors still suffer from low reliability and short life span, particularly in harsh environments. Herein, a conductive, environment-tolerant, stretchable, and healable fiber conductor (CESH), which consists of a self-healable and stretchable organohydrogel fiber core, a conductive and buckled silver nanowire coating, and a self-healable and waterproof protective sheath, is reported. Such a multilayer core-sheath design not only offers high stretchability (≈2400%), high electrical conductivity (1.0 × 106 S m-1 ), outstanding self-healing ability and durability, but also possesses unprecedented tolerance in harsh environments including wide working temperature (-60-20 °C), arid (≈10 % RH (RH: room humidity)), and underwater conditions. As proof-of-concept demonstrations, CESHs are integrated into various wearable formats as interconnectors to steadily perform the electric function under different mechanical deformations and harsh conditions. Such a new type of multifunctional fiber conductors can bridge the gap in stretchable and self-healing fiber technologies by providing ultrastable electrical conductance and excellent environmental tolerance, which can greatly expand the range of applications for fiber conductors.

17.
Adv Mater ; 35(49): e2303550, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37528474

RESUMO

Aqueous zinc batteries have emerged as promising energy storage devices; however, severe parasitic reactions lead to the exacerbated production of Zn dendrites that decrease the utilization rate of Zn anodes. Decreasing the electrolyte content and regulating the water activity are efficient means to address these issues. Herein, this work shows that limiting the aqueous electrolyte and bonding water to bacterial cellulose (BC) can suppress side reactions and regulate stable Zn plating/stripping. This approach makes it possible to use less electrolyte and limited Zn foil. A symmetric Zn cell assembles with the hydrogel electrolyte with limited electrolyte (electrolyte-to-capacity ratio E/C = 1.0 g (Ah)-1 ) cycled stably at a current density of 6.5 mA cm-2 and achieved a capacity of 6.5 mA h cm-2 and depth of discharge of 85%. Full cells with the BC hydrogel electrolyte delivers a discharge capacity of 212 mA h cm-2 and shows a capacity retention of 83% after 1000 cycles at 5 A g-1 . This work offers new fundamental insights into the effect of restricting water to reshape the Zn plating/stripping process and provides a route for designing novel hydrogel electrolytes to better stabilize and efficiently utilize the Zn anodes.

18.
Adv Mater ; 35(49): e2305630, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37566544

RESUMO

Skin electronics provides remarkable opportunities for non-invasive and long-term monitoring of a wide variety of biophysical and physiological signals that are closely related to health, medicine, and human-machine interactions. Nevertheless, conventional skin electronics fabricated on elastic thin films are difficult to adapt to the wet microenvironments of the skin: Elastic thin films are non-permeable, which block the skin perspiration; Elastic thin films are difficult to adhere to wet skin; Most skin electronics are difficult to work underwater. Here, a Wet-Adaptive Electronic Skin (WADE-skin) is reported, which consists of a next-to-skin wet-adhesive fibrous layer, a next-to-air waterproof fibrous layer, and a stretchable and permeable liquid metal electrode layer. While the electronic functionality is determined by the electrode design, this WADE-skin simultaneously offers superb stretchability, wet adhesion, permeability, biocompatibility, and waterproof property. The WADE-skin can rapidly adhere to human skin after contact for a few seconds and stably maintain the adhesion over weeks even under wet conditions, without showing any negative effect to the skin health. The use of WADE-skin is demonstrated for the stable recording of electrocardiogram during intensive sweating as well as underwater activities, and as the strain sensor for the underwater operation of virtual reality-mediated human-machine interactions.


Assuntos
Dispositivos Eletrônicos Vestíveis , Humanos , Eletrônica , Pele , Suor , Eletrocardiografia
19.
Adv Sci (Weinh) ; 10(25): e2300938, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37407509

RESUMO

The antibiotic resistances emerged in uropathogens lead to accumulative treatment failure and recurrent episodes of urinary tract infection (UTI), necessitating more innovative therapeutics to curb UTI before systematic infection. In the current study, the combination of amikacin and nitrofurantoin is found to synergistically eradicate Gram-negative uropathogens in vitro and in vivo. The mechanistic analysis demonstrates that the amikacin, as an aminoglycoside, induced bacterial envelope stress by introducing mistranslated proteins, thereby constitutively activating the cpxA/R two-component system (Cpx signaling). The activation of Cpx signaling stimulates the expression of bacterial major nitroreductases (nfsA/nfsB) through soxS/marA regulons. As a result, the CpxA/R-dependent nitroreductases overexpression generates considerable quantity of lethal reactive intermediates via nitroreduction and promotes the prodrug activation of nitrofurantoin. As such, these actions together disrupt the bacterial cellular redox balance with excessively-produced reactive oxygen species (ROS) as "Domino effect", accelerating the clearance of uropathogens. Although aminoglycosides are used as proof-of-principle to elucidate the mechanism, the synergy between nitrofurantoin is generally applicable to other Cpx stimuli. To summarize, this study highlights the potential of aminoglycoside-nitrofurantoin combination to replenish the arsenal against recurrent Gram-negative uropathogens and shed light on the Cpx signaling-controlled nitroreductase as a potential target to manipulate the antibiotic susceptibility.


Assuntos
Proteínas de Escherichia coli , Infecções Urinárias , Humanos , Nitrofurantoína/farmacologia , Nitrofurantoína/uso terapêutico , Espécies Reativas de Oxigênio/uso terapêutico , Amicacina/uso terapêutico , Escherichia coli/metabolismo , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Aminoglicosídeos/uso terapêutico , Nitrorredutases/uso terapêutico , Proteínas Quinases/metabolismo , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/uso terapêutico
20.
Phys Chem Chem Phys ; 25(28): 18757-18765, 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37427559

RESUMO

Controlling the spatial morphology of the nanorods (NRs) in a polymer matrix and understanding the structure-property relationship are crucial for fabricating high-performance polymer nanocomposites (PNCs). By employing molecular dynamics simulations, we systematically studied the structural and mechanical properties of NR filled PNCs. The simulated results showed that the NRs gradually self-assembled into a three-dimensional (3D) network upon increasing the NR-NR interaction strength. The generated 3D NR network transferred loads along the NR backbone, differing from the well dispersed system which transfers loads between NRs and nearby polymer chains. Increase of the nanorod diameter or NR content further enhanced the PNCs by improving the NR network integrity. These findings provide insights into the reinforcement mechanism of NRs toward polymer matrices and provide guidance for designing PNCs with excellent mechanical performance.

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