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1.
Cell ; 173(3): 762-775.e16, 2018 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-29677517

RESUMO

Mechanotransduction plays a crucial role in vascular biology. One example of this is the local regulation of vascular resistance via flow-mediated dilation (FMD). Impairment of this process is a hallmark of endothelial dysfunction and a precursor to a wide array of vascular diseases, such as hypertension and atherosclerosis. Yet the molecules responsible for sensing flow (shear stress) within endothelial cells remain largely unknown. We designed a 384-well screening system that applies shear stress on cultured cells. We identified a mechanosensitive cell line that exhibits shear stress-activated calcium transients, screened a focused RNAi library, and identified GPR68 as necessary and sufficient for shear stress responses. GPR68 is expressed in endothelial cells of small-diameter (resistance) arteries. Importantly, Gpr68-deficient mice display markedly impaired acute FMD and chronic flow-mediated outward remodeling in mesenteric arterioles. Therefore, GPR68 is an essential flow sensor in arteriolar endothelium and is a critical signaling component in cardiovascular pathophysiology.


Assuntos
Mecanotransdução Celular , Interferência de RNA , Receptores Acoplados a Proteínas G/fisiologia , Animais , Materiais Biocompatíveis , Cálcio/metabolismo , Linhagem Celular Tumoral , Células Endoteliais/fisiologia , Endotélio Vascular/citologia , Células HEK293 , Células Endoteliais da Veia Umbilical Humana , Humanos , Concentração de Íons de Hidrogênio , Artérias Mesentéricas/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico/metabolismo , RNA Interferente Pequeno/metabolismo , Receptores Acoplados a Proteínas G/genética , Resistência ao Cisalhamento , Estresse Mecânico , Resistência Vascular
2.
Nature ; 614(7948): 456-462, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36792740

RESUMO

Stretchable hybrid devices have enabled high-fidelity implantable1-3 and on-skin4-6 monitoring of physiological signals. These devices typically contain soft modules that match the mechanical requirements in humans7,8 and soft robots9,10, rigid modules containing Si-based microelectronics11,12 and protective encapsulation modules13,14. To make such a system mechanically compliant, the interconnects between the modules need to tolerate stress concentration that may limit their stretching and ultimately cause debonding failure15-17. Here, we report a universal interface that can reliably connect soft, rigid and encapsulation modules together to form robust and highly stretchable devices in a plug-and-play manner. The interface, consisting of interpenetrating polymer and metal nanostructures, connects modules by simply pressing without using pastes. Its formation is depicted by a biphasic network growth model. Soft-soft modules joined by this interface achieved 600% and 180% mechanical and electrical stretchability, respectively. Soft and rigid modules can also be electrically connected using the above interface. Encapsulation on soft modules with this interface is strongly adhesive with an interfacial toughness of 0.24 N mm-1. As a proof of concept, we use this interface to assemble stretchable devices for in vivo neuromodulation and on-skin electromyography, with high signal quality and mechanical resistance. We expect such a plug-and-play interface to simplify and accelerate the development of on-skin and implantable stretchable devices.


Assuntos
Eletromiografia , Eletrônica Médica , Nanoestruturas , Maleabilidade , Polímeros , Próteses e Implantes , Dispositivos Eletrônicos Vestíveis , Humanos , Nanoestruturas/química , Polímeros/química , Pele , Monitorização Fisiológica , Eletrônica Médica/instrumentação , Eletrônica Médica/métodos , Eletromiografia/instrumentação
3.
Nature ; 555(7694): 83-88, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29466334

RESUMO

Skin-like electronics that can adhere seamlessly to human skin or within the body are highly desirable for applications such as health monitoring, medical treatment, medical implants and biological studies, and for technologies that include human-machine interfaces, soft robotics and augmented reality. Rendering such electronics soft and stretchable-like human skin-would make them more comfortable to wear, and, through increased contact area, would greatly enhance the fidelity of signals acquired from the skin. Structural engineering of rigid inorganic and organic devices has enabled circuit-level stretchability, but this requires sophisticated fabrication techniques and usually suffers from reduced densities of devices within an array. We reasoned that the desired parameters, such as higher mechanical deformability and robustness, improved skin compatibility and higher device density, could be provided by using intrinsically stretchable polymer materials instead. However, the production of intrinsically stretchable materials and devices is still largely in its infancy: such materials have been reported, but functional, intrinsically stretchable electronics have yet to be demonstrated owing to the lack of a scalable fabrication technology. Here we describe a fabrication process that enables high yield and uniformity from a variety of intrinsically stretchable electronic polymers. We demonstrate an intrinsically stretchable polymer transistor array with an unprecedented device density of 347 transistors per square centimetre. The transistors have an average charge-carrier mobility comparable to that of amorphous silicon, varying only slightly (within one order of magnitude) when subjected to 100 per cent strain for 1,000 cycles, without current-voltage hysteresis. Our transistor arrays thus constitute intrinsically stretchable skin electronics, and include an active matrix for sensory arrays, as well as analogue and digital circuit elements. Our process offers a general platform for incorporating other intrinsically stretchable polymer materials, enabling the fabrication of next-generation stretchable skin electronic devices.


Assuntos
Eletrônica/instrumentação , Maleabilidade , Pele , Transistores Eletrônicos , Dispositivos Eletrônicos Vestíveis , Humanos , Polímeros/química , Silício/química
4.
Mikrochim Acta ; 191(6): 302, 2024 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-38709346

RESUMO

A sensitive and biocompatible N-rich probe for rapid visual uranium detection was constructed by grafting two trianiline groups to 2,6-bis(aminomethyl)pyridine. Possessing excellent aggregation-induced emission (AIE) property and the advantages to form multidentate chelate with U selectively, the probe has been applied successfully to visualize uranium in complex environmental water samples and living cells, demonstrating outstanding anti-interference ability against large equivalent of different ions over a wide effective pH range. A large linear range (1.0 × 10-7-9.0 × 10-7 mol/L) and low detection limit (72.6 nmol/L, 17.28 ppb) were achieved for the visual determination of uranium. The recognition mechanism, photophysical properties, analytical performance and cytotoxicity were systematically investigated, demonstrating high potential for fast risk assessment of uranium pollution in field and in vivo.


Assuntos
Corantes Fluorescentes , Urânio , Urânio/análise , Urânio/química , Corantes Fluorescentes/química , Corantes Fluorescentes/toxicidade , Humanos , Limite de Detecção , Materiais Biocompatíveis/química , Células HeLa , Sobrevivência Celular/efeitos dos fármacos , Imagem Óptica , Compostos de Anilina/química , Compostos de Anilina/toxicidade , Piridinas/química
5.
BMC Oral Health ; 24(1): 179, 2024 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-38311720

RESUMO

OBJECTIVE: To clarify whether the 3D printing model has auxiliary functions in toto extraction of donor tooth in autotransplantation cases. METHODS: Two hundred and sixty patients who would have operation of ATT were divided into two groups. In group 1, determination of the tooth extraction in toto was predicted only according to the clinical and imaging examination. In group 2, the prediction was performed according to the clinical and imaging examination as well as the 3D model of donor tooth pre-extraction. A prespctive clinical study was designed on intra-group comparison between the predicted and actual donor teeth situation when extraction in cases of ATT. The consistent rate for the predicted results and the actual results were compared with the two groups. RESULTS: A remarkable difference was observed between the predicted results and the actual results of tooth positions and root numbers in group without model (p < 0,05). The consistency rate of the model group (94.62%) was significantly higher than that of non 3D model group (86.15%) (p = 0.034). CONCLUSION: The 3D printing model for the donor tooth is helpful for dentists to predict the accuracy of toto extraction of donor teeth in autotransplantation cases.


Assuntos
Compostos de Quinolínio , Cirurgia Assistida por Computador , Tiazóis , Dente , Humanos , Transplante Autólogo/métodos , Cirurgia Assistida por Computador/métodos , Extração Dentária , Impressão Tridimensional
6.
J Am Chem Soc ; 145(32): 17755-17766, 2023 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-37527404

RESUMO

Precise activation of polymer nanoparticles at lesion sites is crucial to achieve favorable therapeutic efficacy. However, conventional endogenous stimuli-responsive polymer nanoparticles probably suffer from few triggers to stimulate the polymer degradation and subsequent functions. Here, we describe oxidation-responsive poly(ferrocene) amphiphiles containing phenylboronic acid ester and ferrocene as the repeating backbone units. Upon triggering by hydrogen peroxide inside the tumor cells, the phenylboronic acid ester bonds are broken and poly(ferrocene) units are degraded to afford free ferrocene and noticeable hydroxide ions. The released hydroxide ions can immediately improve the pH value within the poly(ferrocene) aggregates, and the degradation rate of the phenylboronic acid ester backbone is further promoted by the upregulated pH; thereupon, the accelerated degradation can release much more additional hydroxide ions to improve the pH, thus achieving a positive self-amplified cascade degradation of poly(ferrocene) aggregates accompanied by oxidative stress boosting and efficient cargo release. Specifically, the poly(ferrocene) aggregates can be degraded up to ∼90% within 12 h when triggered by H2O2, while ferrocene-free control nanoparticles are degraded by only 30% within 12 days. In addition, the maleimide moieties tethered in the hydrophilic corona can capture blood albumin to form an albumin-rich protein corona and significantly improve favorable tumor accumulation. The current oxidation-responsive poly(ferrocene) amphiphiles can efficiently inhibit tumors in vitro and in vivo. This work provides a proof-of-concept paradigm for self-amplified polymer degradation and concurrent oxidative stress, which is promising in actively regulated precision medicine.


Assuntos
Peróxido de Hidrogênio , Nanopartículas , Peróxido de Hidrogênio/química , Polímeros/farmacologia , Polímeros/química , Estresse Oxidativo , Concentração de Íons de Hidrogênio , Albuminas , Ésteres , Nanopartículas/química
7.
Ophthalmic Physiol Opt ; 43(5): 1070-1078, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37310193

RESUMO

PURPOSE: To present the objective metrics from a study that evaluated the clinical performance of a senofilcon A contact lens, both with and without a new manufacturing technique. METHODS: This was a single-site, five-visit, controlled, randomised, subject-masked, 2 × 2 crossover study (May-August 2021) with a 2-week lens dispensing period (bilateral wear) and weekly follow-up visits. Healthy adult (18-39 years), habitual spherical silicone hydrogel contact lens wearers were included. The High-definition (HD) Analyzer™ was used to objectively measure the lens-on-eye optical system resulting from the study lenses at 1-week follow-up. Measurements assessed were vision break-up time (VBUT), modulation transfer function (MTF) cutoff, Strehl ratio (SR), potential visual acuity (PVA) for 100% contrast and objective scatter index (OSI). RESULTS: Of the 50 enrolled participants, 47 (94.0%) were randomly assigned to one of the two possible lens wear sequences (test/control or control/test) and dispensed at least one study lens. The estimated odds ratio of VBUT > 10 s was 1.582 (95% confidence interval [CI]: 1.009 to 2.482) in test versus control lens. The least squares mean difference estimates of MTF cutoff, SR and PVA for 100% contrast between test versus control lens were 2.243 (95% CI: 0.012 to 4.475), 0.011 (95% CI: -0.002 to 0.023) and 0.073 (95% CI: -0.001 to 0.147), respectively. The estimated ratio of median OSI between test versus control lens was 0.887 (95% CI: 0.727 to 1.081). The test lens demonstrated superiority over the control lens with respect to VBUT and MTF cutoff. No serious adverse events were reported; eight adverse events (three ocular, five non-ocular) were indicated by six participants during the study. CONCLUSION: The test lens demonstrated an increased probability of having a longer VBUT (>10 s). Future studies may be designed to assess the efficacy and long-term use of the test lens in a larger population.


Assuntos
Lentes de Contato Hidrofílicas , Adulto , Humanos , Estudos Cross-Over , Lentes de Contato Hidrofílicas/efeitos adversos , Acuidade Visual , Visão Ocular , Silicones , Lágrimas
8.
Int Wound J ; 20(10): 4340-4348, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37437962

RESUMO

A meta-analysis was performed to assess the effects of different regenerative technologies and materials on wound healing after surgical endodontic therapy and provide a reference for surgical endodontic treatment. We searched for studies on the use of regenerative technologies and materials in surgical endodontic therapy via PubMed, MEDLINE, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Data from the time of database creation to December 2022. Two researchers independently screened the literature, extracted information based on the inclusion and exclusion criteria, and evaluated the quality of the included studies. A meta-analysis was performed using Review Manager 5.4. The results showed that the use of regenerative technologies and materials significantly reduced wound healing failures (risk ratio [RR]: 0.30, 95% confidence intervals [CI]: 0.22-0.40, p < 0.001). Moreover, autologous platelet concentrations (APCs) (RR: 0.28, 95% CI: 0.15-0.53, p < 0.001) and collagen membrane plus bovine-derived hydroxyapatite (RR: 0.27, 95% CI. 0.12-0.61, p = 0.002) were more effective in improving wound healing failure rates than collagen membrane alone (RR: 0.51, 95% CI: 0.20-1.25, p = 0.140). Our findings showed that APCs, as well as collagen membrane plus bovine-derived hydroxyapatite, significantly improved wound healing after surgical endodontic therapy. In contrast, collagen membrane alone did not significantly improve wound healing outcomes. However, currently available studies vary significantly in sample size and methodologies. Hence, high-quality randomised controlled studies with large sample sizes are necessary to validate our findings.


Assuntos
Colágeno , Cicatrização , Humanos , Animais , Bovinos , Hidroxiapatitas , China
9.
Angew Chem Int Ed Engl ; 62(30): e202303829, 2023 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-37235518

RESUMO

Amphiphilic self-immolative polymers (SIPs) can achieve complete degradation solely through one triggerable event, which potentially optimize the blood clearance and uncontrollable/inert degradability for therapeutic nanoparticles. Herein, we report self-immolative amphiphilic poly(ferrocenes), BPnbs -Fc, composed by self-immolative backbone and aminoferrocene (AFc) side chains as well as end-capping poly(ethylene glycol) monomethyl ether. Upon triggering by tumor acidic milieu, the BPnbs -Fc nanoparticles readily degrade to release azaquinone methide (AQM) moieties, which can rapidly deplete intracellular glutathione (GSH) to cascade release AFc. Furthermore, both AFc and its product Fe2+ can catalyze intracellular hydrogen peroxide (H2 O2 ) into highly reactive hydroxyl radicals (⋅OH), thus amplifying the oxidative stress of tumor cells. Rational synergy of GSH depletion and ⋅OH burst can efficiently inhibit tumor growth by the SIPs in vitro and in vivo. This work provides an elegant design to adopt innate tumor milieu-triggerable SIPs degradation to boost cellular oxidative stress, which is a promising candidate for precision medicine.


Assuntos
Nanopartículas , Neoplasias , Humanos , Metalocenos , Polietilenoglicóis/química , Estresse Oxidativo , Polímeros/química , Neoplasias/tratamento farmacológico , Peróxido de Hidrogênio/metabolismo , Linhagem Celular Tumoral , Nanopartículas/química , Glutationa/metabolismo
10.
Angew Chem Int Ed Engl ; 62(3): e202214695, 2023 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-36412223

RESUMO

The use of sequence-defined digital polymers for data storage and encryption has received increasing attention due to their precision structures similar to natural biomacromolecules (e.g., DNA) but increased stability. However, the rapid development of sequencing techniques raises the concern of information leakage. Herein, dendritic quaternary-encoded oligourethanes bearing a photoresponsive trigger, self-immolative backbones, and a mass spectrometry tag of PEG dendron have been developed for data encryption. Although the sequence information in linear analogs can be readily deciphered by mass spectrometry, sequencing of dendritic oligourethanes cannot be achieved by either primary MS or tandem MS/MS owing to the unique spatial conformation. Intriguingly, the fragmentation pathways of a quaternary dendrimer under MS/MS conditions can be converted to 2772-bit 2D matrices with ≈1.98×1087 permutations, serving as high-strength encryption keys for highly reliable data encryption.


Assuntos
Segurança Computacional , Espectrometria de Massas em Tandem , Polímeros , DNA , Armazenamento e Recuperação da Informação
11.
Angew Chem Int Ed Engl ; 62(26): e202303600, 2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37041661

RESUMO

Bimetallic alloy nanomaterials are promising anode materials for potassium-ion batteries (KIBs) due to their high electrochemical performance. The most well-adopted fabrication method for bimetallic alloy nanomaterials is tube furnace annealing (TFA) synthesis, which can hardly satisfy the trade-off among granularity, dispersity and grain coarsening due to mutual constraints. Herein, we report a facile, scalable and ultrafast high-temperature radiation (HTR) method for the fabrication of a library of ultrafine bimetallic alloys with narrow size distribution (≈10-20 nm), uniform dispersion and high loading. The metal-anchor containing heteroatoms (i.e., O and N), ultrarapid heating/cooling rate (≈103  K s-1 ) and super-short heating duration (several seconds) synergistically contribute to the successful synthesis of small-sized alloy anodes. As a proof-of-concept demonstration, the as-prepared BiSb-HTR anode shows ultrahigh stability indicated by negligible degradation after 800 cycles. The in situ X-ray diffraction reveals the K+ storage mechanism of BiSb-HTR. This study can shed light on the new, rapid and scalable nanomanufacturing of high-quality bimetallic alloys toward extended applications of energy storage, energy conversion and electrocatalysis.


Assuntos
Ligas , Potássio , Biblioteca Gênica , Temperatura Baixa , Eletrodos , Íons
12.
Nature ; 539(7629): 411-415, 2016 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-27853213

RESUMO

Thin-film field-effect transistors are essential elements of stretchable electronic devices for wearable electronics. All of the materials and components of such transistors need to be stretchable and mechanically robust. Although there has been recent progress towards stretchable conductors, the realization of stretchable semiconductors has focused mainly on strain-accommodating engineering of materials, or blending of nanofibres or nanowires into elastomers. An alternative approach relies on using semiconductors that are intrinsically stretchable, so that they can be fabricated using standard processing methods. Molecular stretchability can be enhanced when conjugated polymers, containing modified side-chains and segmented backbones, are infused with more flexible molecular building blocks. Here we present a design concept for stretchable semiconducting polymers, which involves introducing chemical moieties to promote dynamic non-covalent crosslinking of the conjugated polymers. These non-covalent crosslinking moieties are able to undergo an energy dissipation mechanism through breakage of bonds when strain is applied, while retaining high charge transport abilities. As a result, our polymer is able to recover its high field-effect mobility performance (more than 1 square centimetre per volt per second) even after a hundred cycles at 100 per cent applied strain. Organic thin-film field-effect transistors fabricated from these materials exhibited mobility as high as 1.3 square centimetres per volt per second and a high on/off current ratio exceeding a million. The field-effect mobility remained as high as 1.12 square centimetres per volt per second at 100 per cent strain along the direction perpendicular to the strain. The field-effect mobility of damaged devices can be almost fully recovered after a solvent and thermal healing treatment. Finally, we successfully fabricated a skin-inspired stretchable organic transistor operating under deformations that might be expected in a wearable device.


Assuntos
Materiais Biomiméticos/química , Biomimética , Polímeros/química , Transistores Eletrônicos , Humanos , Maleabilidade , Pele , Estresse Mecânico , Cicatrização
13.
Molecules ; 27(1)2021 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-35011406

RESUMO

The application of chitosan (CS) and whey protein (WP) alone or in combination in 3D/4D printing has been well considered in previous studies. Although several excellent reviews on additive manufacturing discussed the properties and biomedical applications of CS and WP, there is a lack of a systemic review about CS and WP bio-inks for 3D/4D printing applications. Easily modified bio-ink with optimal printability is a key for additive manufacturing. CS, WP, and WP-CS complex hydrogel possess great potential in making bio-ink that can be broadly used for future 3D/4D printing, because CS is a functional polysaccharide with good biodegradability, biocompatibility, non-immunogenicity, and non-carcinogenicity, while CS-WP complex hydrogel has better printability and drug-delivery effectivity than WP hydrogel. The review summarizes the current advances of bio-ink preparation employing CS and/or WP to satisfy the requirements of 3D/4D printing and post-treatment of materials. The applications of CS/WP bio-ink mainly focus on 3D food printing with a few applications in cosmetics. The review also highlights the trends of CS/WP bio-inks as potential candidates in 4D printing. Some promising strategies for developing novel bio-inks based on CS and/or WP are introduced, aiming to provide new insights into the value-added development and commercial CS and WP utilization.


Assuntos
Materiais Biocompatíveis , Quitosana/química , Indústria Alimentícia , Tinta , Impressão Tridimensional , Proteínas do Soro do Leite/química , Antocianinas/química , Géis/química , Probióticos/administração & dosagem , Probióticos/química
14.
Sheng Li Xue Bao ; 73(6): 999-1016, 2021 Dec 25.
Artigo em Zh | MEDLINE | ID: mdl-34961875

RESUMO

Cellular primary cilium, located on the surface of virtually all mammalian cells, is a strictly conserved organelle which regulates cell biological process and maintains cell homeostasis by modulating cell proliferation, differentiation, migration, polarity, signal cascades and other life activities. Some diseases caused by mutations in genes encoding structural proteins or accessory proteins of primary cilia are collectively termed as "ciliopathies", which can occur in embryo, infancy and even adulthood. Ciliopathies not only involve a single organ, but also involve multiple organs and multiple systems, showing variable symptoms and overlapping symptoms. This review mainly summarizes the effects of ciliopathy-associated gene mutations on bone, tooth, skin, liver and bile duct, kidney, brain, retina, heart and other organs, uncovers their molecular mechanisms and provides some novel insights into therapy of ciliopathies.


Assuntos
Cílios , Ciliopatias , Adulto , Animais , Ciliopatias/genética , Humanos , Proteínas , Retina , Transdução de Sinais
15.
J Infect Dis ; 222(3): 443-455, 2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32115640

RESUMO

BACKGROUND: Encephalitis in hand, foot, and mouth disease (HFMD) is a serious threat to children's health and life. Toll-like receptor 3 (TLR3) is an innate immune-recognition receptor that can recognize virus and initiate innate immune responses. Emodin has the effects of anti-inflammatory and regulating immune function, but the mechanism is not very clear. METHODS: Cells and mice were pretreated with coxsackievirus B3m (CVB3) and treated with emodin. The messenger ribonucleic acid (mRNA) and protein levels of TLR3 and downstream molecules were detected by quantitative real-time polymearse chain reaction and western blotting analysis, respectively. TLR3 expression was also downregulated by anti-TLR3 antibody (TLR3Ab) or small interfering RNA (siRNA). Pathological changes were assessed with hematoxylin and eosin staining. Immunohistochemistry was used to examine the expression of TLR3 in brain tissues. The expression of interleukin (IL)-6, nuclear factor (NF)-κB, and interferon (IFN)-ß in serum were tested with enzyme-linked immunosorbent assay. RESULTS: Emodin decreased the mRNA and protein levels of TLR3 and downstream molecules in vitro and in vivo. After downregulating TLR3 using anti-TLR3Ab or siRNA, emodin could still decrease the mRNA and protein levels of TLR3 and downstream molecules. Emodin also displayed notable effects on pathology, TLR3 protein in brain tissues, and expression of IL-6, NF-κB, IFN-ß, in serum. CONCLUSIONS: Emodin exerts a protective effect in CVB3-mediated encephalitis in HFMD by inhibiting the TLR3 pathway.


Assuntos
Emodina/farmacologia , Encefalite/tratamento farmacológico , Doença de Mão, Pé e Boca/virologia , Transdução de Sinais/efeitos dos fármacos , Receptor 3 Toll-Like/metabolismo , Animais , Western Blotting , Células Cultivadas , Encefalite/imunologia , Encefalite/virologia , Enterovirus/imunologia , Ensaio de Imunoadsorção Enzimática , Imunidade Inata , Interferon beta/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , RNA Mensageiro/efeitos dos fármacos , Receptor 3 Toll-Like/genética
16.
Rheumatology (Oxford) ; 59(10): 3070-3080, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32417913

RESUMO

OBJECTIVES: IL-37 has been identified as an important anti-inflammatory and immunosuppressive factor. This study was undertaken to explore how IL-37 affects M1/M2-like macrophage polarization and thus contributes to anti-inflammatory processes in the temporomandibular joint. METHODS: Western blotting, quantitative real-time PCR (qRT-PCR) and immunofluorescence were used to verify the IL-37-induced polarization shift from the M1 phenotype to the M2 phenotype, and the related key pathways were analysed by western blotting. Human chondrocytes were stimulated with M1-conditioned medium (CM) or IL-37-pretreated M1-CM, and inflammatory cytokines were detected. siRNA-IL-1R8 and MCC-950 were used to investigate the mechanism underlying the anti-inflammatory effects of IL-37. Complete Freund's adjuvant-induced and disc perforation-induced inflammation models were used for in vivo studies. Haematoxylin and eosin, immunohistochemical and safranin-O staining protocols were used to analyse histological changes in the synovium and condyle. RESULTS: Western blotting, qRT-PCR and immunofluorescence showed that IL-37 inhibited M1 marker expression and upregulated M2 marker expression. Western blotting and qRT-PCR showed that pretreatment with IL-37 suppressed inflammatory cytokine expression in chondrocytes. IL-37 inhibited the expression of NLRP3 and upregulated the expression of IL-1R8. Si-IL-1R8 and MCC-950 further confirmed that the anti-inflammatory properties of IL-37 were dependent on the presence of IL-1R8 and NLRP3. In vivo, IL-37 reduced synovial M1 marker expression and cartilage degeneration and increased M2 marker expression. CONCLUSION: IL-37 shifting of the polarization of macrophages from the pro-inflammatory M1 phenotype to the beneficial anti-inflammatory M2 phenotype seems to be a promising therapeutic strategy for treating temporomandibular joint inflammation.


Assuntos
Polaridade Celular/efeitos dos fármacos , Interleucina-1/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Transtornos da Articulação Temporomandibular/terapia , Western Blotting , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Meios de Cultivo Condicionados/farmacologia , Citocinas/metabolismo , Adjuvante de Freund , Furanos , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Humanos , Indenos , Inflamassomos/efeitos dos fármacos , Macrófagos/metabolismo , Côndilo Mandibular/patologia , Osteoartrite/induzido quimicamente , Osteoartrite/metabolismo , Osteoartrite/patologia , Osteoartrite/terapia , RNA Interferente Pequeno/farmacologia , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Interleucina-1/metabolismo , Sulfonamidas , Sulfonas/farmacologia , Membrana Sinovial/patologia , Transtornos da Articulação Temporomandibular/induzido quimicamente , Transtornos da Articulação Temporomandibular/metabolismo , Transtornos da Articulação Temporomandibular/patologia , Regulação para Cima
17.
Bull Environ Contam Toxicol ; 105(5): 742-749, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000334

RESUMO

Inland lakes are important ecosystems for the carbon cycle at both regional and global scales. However, a knowledge gap still exists about the correlations between the partial pressure of CO2 (pCO2) and nutrient dynamics in lakes. In this study, we analysed the long-term dynamics of nutrient and pCO2 in Taihu Lake. Strong spatial heterogeneity was observed with highest nutrient concentrations occurring in the River mouth and significant lower concentrations (p < 0.01) occurring in East Taihu and Other zone. For pCO2, the average values were 1136.81 ± 1240.16 µatm, 433.07 ± 305.45 µatm, and 487.05 ± 414.02 µatm in Rive mouth, East Taihu, and Other zone, respectively. Statistical analysis revealed that pCO2 was significantly and positively related to nutrient (TN: total nitrogen and NH4+: ammonium) concentrations (p < 0.01), but negatively related to Chla (Chlorophyll a) concentrations in River mouth and Other zone (p < 0.01). The parallelism of nutrient concentrations and pCO2 in Taihu Lake highlights the dual effects of external pollution inputs from the surrounding catchment. In addition, progressive mitigation was found for not only nutrients but also pCO2, which was attributed to the previous effort in the environmental protections in Taihu Lake basin. Our results also suggest the importance of long-term monitoring for the future assessment of anthropogenic impacts on nutrient and CO2 dynamics in freshwater lakes.


Assuntos
Dióxido de Carbono/análise , Monitoramento Ambiental/métodos , Lagos/química , Nitrogênio/análise , Fósforo/análise , Poluentes Químicos da Água/análise , China , Clorofila A/análise , Ecossistema , Eutrofização , Rios/química
18.
Acc Chem Res ; 51(5): 1033-1045, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29693379

RESUMO

Future electronics will take on more important roles in people's lives. They need to allow more intimate contact with human beings to enable advanced health monitoring, disease detection, medical therapies, and human-machine interfacing. However, current electronics are rigid, nondegradable and cannot self-repair, while the human body is soft, dynamic, stretchable, biodegradable, and self-healing. Therefore, it is critical to develop a new class of electronic materials that incorporate skinlike properties, including stretchability for conformable integration, minimal discomfort and suppressed invasive reactions; self-healing for long-term durability under harsh mechanical conditions; and biodegradability for reducing environmental impact and obviating the need for secondary device removal for medical implants. These demands have fueled the development of a new generation of electronic materials, primarily composed of polymers and polymer composites with both high electrical performance and skinlike properties, and consequently led to a new paradigm of electronics, termed "skin-inspired electronics". This Account covers recent important advances in skin-inspired electronics, from basic material developments to device components and proof-of-concept demonstrations for integrated bioelectronics applications. To date, stretchability has been the most prominent focus in this field. In contrast to strain-engineering approaches that extrinsically impart stretchability into inorganic electronics, intrinsically stretchable materials provide a direct route to achieve higher mechanical robustness, higher device density, and scalable fabrication. The key is the introduction of strain-dissipation mechanisms into the material design, which has been realized through molecular engineering (e.g., soft molecular segments, dynamic bonds) and physical engineering (e.g., nanoconfinement effect, geometric design). The material design concepts have led to the successful demonstrations of stretchable conductors, semiconductors, and dielectrics without sacrificing their electrical performance. Employing such materials, innovative device design coupled with fabrication method development has enabled stretchable sensors and displays as input/output components and large-scale transistor arrays for circuits and active matrixes. Strategies to incorporate self-healing into electronic materials are the second focus of this Account. To date, dynamic intermolecular interactions have been the most effective approach for imparting self-healing properties onto polymeric electronic materials, which have been utilized to fabricate self-healing sensors and actuators. Moreover, biodegradability has emerged as an important feature in skin-inspired electronics. The incorporation of degradable moieties along the polymer backbone allows for degradable conducting polymers and the use of bioderived materials has led to the demonstration of biodegradable functional devices, such as sensors and transistors. Finally, we highlight examples of skin-inspired electronics for three major applications: prosthetic e-skins, wearable electronics, and implantable electronics.


Assuntos
Eletrônica Médica/instrumentação , Polímeros/química , Plásticos Biodegradáveis/química , Humanos , Fenômenos Mecânicos , Próteses e Implantes , Transistores Eletrônicos , Dispositivos Eletrônicos Vestíveis
19.
J Oral Maxillofac Surg ; 77(8): 1582-1593, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30904552

RESUMO

PURPOSE: Idiopathic condylar resorption (ICR) is an aggressive form of osteoarthritis that is frequently observed in adolescent female patients. We hypothesized that an estrogen-mediated pathway may contribute to ICR development. MATERIALS AND METHODS: An enzyme-linked immunosorbent assay was used to detect the levels of estradiol (E2) and hyaluronan in synovial fluid. Immunohistochemistry, real-time polymerase chain reaction, and Western blotting were used to detect the expression of microRNAs (miRNAs) and related genes after transfection of miRNA-101-3p mimics, inhibitor, or short interfering RNA into synovial fibroblasts. Dual-luciferase activity was determined to identify the direct effect of miRNA-101-3p on hyaluronan synthase 2 (HAS2). Linear regression analysis, the nonparametric Mann-Whitney U test, the Student t test, and 1-way analysis of variance were carried out to analyze the results of each group. RESULTS: The relationship between hyaluronan and E2 was negatively correlated in synovial fluid (Pearson r = -0.3179, P = .0230). Among the screened miRNAs, miRNA-101-3p was the most overexpressed in ICR. E2 mostly upregulated the expression of miRNA-101-3p at a dose of 10 nmol/L 12 hours after transfection in synovial fibroblasts of patients with ICR. However, E2 induction of miRNA-101-3p expression was significantly repressed by estrogen receptor α interference (P = 0.0286). The dual-luciferase assay showed that miRNA-101-3p regulated the expression of HAS2 by directly targeting its 3' untranslated region. CONCLUSIONS: We speculate that E2 regulates HAS2 expression by targeting miRNA-101-3p in synovial fibroblasts of patients with ICR. Thus, the E2-miRNA-101-3p-HAS2 pathway might play an important role in the pathogenesis of ICR.


Assuntos
Reabsorção Óssea , Estrogênios , Hialuronan Sintases , MicroRNAs , Osteoartrite , Adolescente , Reabsorção Óssea/genética , Reabsorção Óssea/patologia , Estrogênios/fisiologia , Feminino , Fibroblastos/metabolismo , Humanos , Hialuronan Sintases/metabolismo , Côndilo Mandibular , MicroRNAs/metabolismo
20.
BMC Microbiol ; 18(1): 221, 2018 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-30577728

RESUMO

BACKGROUND: The microflora composition of the oral cavity affects oral health. Some strains of commensal bacteria confer probiotic benefits to the host. Lactobacillus is one of the main probiotic genera that has been used to treat oral infections. The objective of this study was to select lactobacilli with a spectrum of probiotic properties and investigate their potential roles in oral health. RESULTS: An oral isolate characterized as Lactobacillus brevis BBE-Y52 exhibited antimicrobial activities against Streptococcus mutans, a bacterial species that causes dental caries and tooth decay, and secreted antimicrobial compounds such as hydrogen peroxide and lactic acid. Compared to other bacteria, L. brevis BBE-Y52 was a weak acid producer. Further studies showed that this strain had the capacity to adhere to oral epithelial cells. Co-incubation of L. brevis BBE-Y52 with S. mutans ATCC 25175 increased the IL-10-to-IL-12p70 ratio in peripheral blood mononuclear cells, which indicated that L. brevis BBE-Y52 could alleviate inflammation and might confer benefits to host health by modulating the immune system. CONCLUSIONS: L. brevis BBE-Y52 exhibited a spectrum of probiotic properties, which may facilitate its applications in oral care products.


Assuntos
Cárie Dentária/microbiologia , Levilactobacillus brevis/fisiologia , Probióticos/isolamento & purificação , Adulto , Cárie Dentária/tratamento farmacológico , Feminino , Humanos , Levilactobacillus brevis/genética , Levilactobacillus brevis/isolamento & purificação , Masculino , Boca/microbiologia , Probióticos/administração & dosagem , Saliva/microbiologia , Streptococcus mutans/fisiologia , Adulto Jovem
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