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The limitations of two-dimensional (2D) graphene in broadband photodetector are overcome by integrating nitrogen (N) doping into three-dimensional (3D) structures within silicon (Si) via plasma-assisted chemical vapor deposition (PACVD) technology. This contributes to the construction of vertical Schottky heterojunction broad-spectrum photodetectors and applications in logic devices and image sensors. The natural nanoscale resonant cavity structure of 3D-graphene enhances photon capture efficiency, thereby increasing photocarrier generation. N-doping can fine-tune the electronic structure, advancing the Schottky barrier height and reducing dark current. The as-fabricated photodetector exhibits exceptional self-driven photoresponse, especially at 1550 nm, with an excellent photoresponsivity (79.6 A/W), specific detectivity (1013 Jones), and rapid response of 130 µs. Moreover, it enables logic circuits, high-resolution pattern image recognition, and broadband spectra recording across the visible to near-infrared range (400-1550 nm). This research will provide new views and technical support for the development and widespread application of high-performance semiconductor-based graphene broadband detectors.
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Skin macrophages are critical to maintain and restore skin homeostasis. They serve as major producers of cytokines and chemokines in the skin, participating in diverse biological processes such as wound healing and psoriasis. The heterogeneity and functional diversity of macrophage subpopulations endow them with multifaceted roles in psoriasis development. A distinct subpopulation of skin macrophages, characterized by high expression of CD169, has been reported to exist in both mouse and human skin. However, its role in psoriasis remains unknown. Here, we report that CD169+ macrophages exhibit increased abundance in imiquimod (IMQ) induced psoriasis-like skin lesions. Specific depletion of CD169+ macrophages in CD169-ditheria toxin receptor (CD169-DTR) mice inhibits IMQ-induced psoriasis, resulting in milder symptoms, diminished proinflammatory cytokine levels and reduced proportion of Th17 cells within the skin lesions. Furthermore, transcriptomic analysis uncovers enhanced activity in CD169+ macrophages when compared with CD169- macrophages, characterized by upregulated genes that are associated with cell activation and cell metabolism. Mechanistically, CD169+ macrophages isolated from IMQ-induced skin lesions produce more proinflammatory cytokines and exhibit enhanced ability to promote Th17 cell differentiation in vitro. Collectively, our findings highlight the crucial involvement of CD169+ macrophages in psoriasis development and offer novel insights into the heterogeneity of skin macrophages in the context of psoriasis.
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Imiquimod , Macrófagos , Psoriasis , Lectina 1 Similar a Ig de Unión al Ácido Siálico , Piel , Animales , Psoriasis/inmunología , Psoriasis/metabolismo , Psoriasis/patología , Psoriasis/inducido químicamente , Psoriasis/genética , Macrófagos/metabolismo , Macrófagos/inmunología , Ratones , Piel/metabolismo , Piel/patología , Piel/inmunología , Lectina 1 Similar a Ig de Unión al Ácido Siálico/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Células Th17/inmunología , Células Th17/metabolismo , Diferenciación Celular , Ratones Endogámicos C57BLRESUMEN
Wearable soft contact lens sensors for continuous and nondestructive intraocular pressure (IOP) monitoring are highly desired as glaucoma and postoperative myopia patients grow, especially as the eyestrain crowd increases. Herein, a smart closed-loop system is presented that combines a Ti3C2Tx MXene-based soft contact lens (MX-CLS) sensor, wireless data transmission units, display, and warning components to realize continuous and nondestructive IOP monitoring/real-time display. The fabricated MX-CLS device exhibits an extremely high sensitivity of 7.483 mV mmHg-1, good linearity on silicone eyeballs, excellent stability under long-term pressure-release measurement, sufficient transparency with 67.8% transmittance under visible illumination, and superior biocompatibility with no discomfort when putting the MX-CLS sensor onto the Rabbit eyes. After integrating with the wireless module, users can realize real-time monitoring and warning of IOP via smartphones, the demonstrated MX-CLS device together with the IOP monitoring/display system opens up promising platforms for Ti3C2Tx materials as the base for multifunctional contact lens-based sensors and continuous and nondestructive IOP measurement system.
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Lentes de Contacto Hidrofílicos , Presión Intraocular , Titanio , Presión Intraocular/fisiología , Animales , Conejos , Titanio/química , Monitoreo Fisiológico/métodos , Monitoreo Fisiológico/instrumentaciónRESUMEN
A breakthrough in the performance of bionic optical structures will only be achieved if we can obtain an in-depth understanding of the synergy mechanisms operating in natural optical structures and find ways to imitate them. In this work, inspired by feline eyes, an optical substrate that takes advantage of a synergistic effect that occurs between resonant and reflective structures was designed. The synergistic effect between the reflective and resonant components leads to a Raman enhancement factor (EF) of 1.16 × 107, which is much greater than that achieved using the reflective/resonant cavities on their own. Finite-difference time-domain (FDTD) simulations and experimental results together confirm that the mechanism of this synergistic effect is achieved by realizing multiple reflections and repeated absorptions of light, generating a strong local electric field. Thus, a 2-3 order of magnitude increase in sensitivity could be achieved. More importantly, with the homemade centrifugal device, above optical substrates were further used to develop a rapidly highly sensitive household health monitoring system (detection time <3 min). It can thus be used to give early warning of acute diseases with high risk (e.g., acute myocardial infarction (AMI) and cerebral peduncle). Due to the good reusability and storability (9% and 8% reduction in EF after washing 30 times and 9 months of storage, respectively) of the substrates, the substrates thus reduce detection costs (to â¼$1), making them much cheaper to use than the current gold-standard methods (e.g., â¼$16 for gout detection).
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Espectrometría Raman , Gatos , Animales , Humanos , Espectrometría Raman/métodos , Enfermedad CrónicaRESUMEN
Precise monitoring of internal temperature is vital for thermal homeostasis in mammals. For decades, warm-sensitive neurons (WSNs) within the preoptic area (POA) were thought to sense internal warmth, using this information as feedback to regulate body temperature (Tcore). However, the cellular and molecular mechanisms by which WSNs measure temperature remain largely undefined. Via a pilot genetic screen, we found that silencing the TRPC4 channel in mice substantially attenuated hypothermia induced by light-mediated heating of the POA. Loss-of-function studies of TRPC4 confirmed its role in warm sensing in GABAergic WSNs, causing additional defects in basal temperature setting, warm defense, and fever responses. Furthermore, TRPC4 antagonists and agonists bidirectionally regulated Tcore. Thus, our data indicate that TRPC4 is essential for sensing internal warmth and that TRPC4-expressing GABAergic WSNs function as a novel cellular sensor for preventing Tcore from exceeding set-point temperatures. TRPC4 may represent a potential therapeutic target for managing Tcore.
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Regulación de la Temperatura Corporal , Temperatura Corporal , Ratones , Animales , Temperatura Corporal/fisiología , Regulación de la Temperatura Corporal/fisiología , Hipotálamo , Área Preóptica/fisiología , Neuronas GABAérgicas , MamíferosRESUMEN
Follicular dendritic cells (FDCs) are a specialized type of stromal cells that exclusively reside in B-cell follicles. When inflammation occurs, the FDC network is reorganized to support germinal center (GC) polarization into the light zone (LZ) and dark zone (DZ). Despite the indispensable role of FDCs in supporting humoral responses, the FDC regulatory requirements remain incompletely defined. In this study, we unexpectedly observed an accumulation of CD169+ subcapsular sinus macrophage (SSM)-derived microvesicles (MVs) in the B-cell zone, which were tightly associated with the FDC network. Interestingly, a selective deposition of CD169+ MVs was detected in both GC LZ FDCs in secondary follicles and on predetermined LZ FDCs in primary follicles. The ablation of CD169+ MVs, resulting from SSM depletion, resulted in significantly decreased expression of LZ-related genes in FDCs. In addition, we found that CD169+ MVs could colocalize with fluorescently tagged antigen-containing immune complexes (ICs), supporting a possible role of CD169+ MVs in transporting antigens to the FDC network. Thus, our data reveal intimate crosstalk between FDCs and SSMs located outside B-cell follicles via SSM-released MVs, providing a novel perspective on the mechanisms underlying the regulation of FDC maturation and polarization.
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Complejo Antígeno-Anticuerpo , Células Dendríticas Foliculares , Complejo Antígeno-Anticuerpo/metabolismo , Antígenos/metabolismo , Linfocitos B , Células Dendríticas , Centro Germinal , MacrófagosRESUMEN
Flexible multichannel electrode arrays (fMEAs) with multiple filaments can be flexibly implanted in various patterns. It is necessary to develop a method for implanting the fMEA in different locations and at various depths based on the recording demands. This study proposed a strategy for reducing the microelectrode volume with integrated packaging. An implantation system was developed specifically for semiautomatic distributed implantation. The feasibility and convenience of the fMEA and implantation platform were verified in rodents. The acute and chronic recording results provied the effectiveness of the packaging and implantation methods. These methods could provide a novel strategy for developing fMEAs with more filaments and recording sites to measure functional interactions across multiple brain regions.
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Three-dimensional graphene (3D-graphene) is used in surface-enhanced Raman spectroscopy (SERS) because of its plasmonic nanoresonator structure and good ability to interact with light. However, a thin (3-5 nm) layer of amorphous carbon (AC) inevitably appears as a template layer between the 3D-graphene and object substrate when the 3D-graphene layer is synthesized, weakening the enhancement factor. Herein, two-dimensional graphene (2D-graphene) is employed as a template layer to directly synthesize 3D-graphene on a germanium (Ge) substrate via plasma-assisted chemical vapor deposition, bypassing the formation of an AC layer. The interaction and photoinduced charge transfer ability of the 3D-graphene/Ge heterojunction with incident light are improved. Moreover, the high density of electronic states close to the Fermi level of the heterojunction induces the adsorbed probe molecules to efficiently couple to the 3D-graphene-based SERS substrate. Our experimental results imply that the lowest concentrations of rhodamine 6G and rhodamine B that can be detected on the 3D/2D-graphene/Ge SERS substrate correspond to 10-10 M; for methylene blue, it is 10-8 M. The detection limits of the 3D/2D-graphene/Ge SERS substrate with respect to 3-hydroxytyramine hydrochloride and melamine (in milk) are both less than 1 ppm. This work may provide a viable and convenient alternative method for preparing 3D-graphene SERS substrates. It also constitutes a new approach to developing SERS substrates with remarkable performance levels.
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Long noncoding RNAs are widely implicated in diverse disease processes. Nonetheless, their regulatory roles in bone resorption are undefined. Here, we identify lncRNA Nron as a critical suppressor of bone resorption. We demonstrate that osteoclastic Nron knockout mice exhibit an osteopenia phenotype with elevated bone resorption activity. Conversely, osteoclastic Nron transgenic mice exhibit lower bone resorption and higher bone mass. Furthermore, the pharmacological overexpression of Nron inhibits bone resorption, while caused apparent side effects in mice. To minimize the side effects, we further identify a functional motif of Nron. The delivery of Nron functional motif to osteoclasts effectively reverses bone loss without obvious side effects. Mechanistically, the functional motif of Nron interacts with E3 ubiquitin ligase CUL4B to regulate ERα stability. These results indicate that Nron is a key bone resorption suppressor, and the lncRNA functional motif could potentially be utilized to treat diseases with less risk of side effects.
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Osteoporosis/genética , Osteoporosis/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Animales , Enfermedades Óseas Metabólicas/etiología , Enfermedades Óseas Metabólicas/genética , Enfermedades Óseas Metabólicas/metabolismo , Resorción Ósea/genética , Resorción Ósea/metabolismo , Resorción Ósea/prevención & control , Proteínas Cullin/metabolismo , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Femenino , Fémur/diagnóstico por imagen , Fémur/metabolismo , Fémur/patología , Inyecciones Intravenosas , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Osteoclastos/metabolismo , Osteoclastos/patología , Osteoporosis/terapia , ARN Largo no Codificante/administración & dosificación , Ubiquitinación , Regulación hacia Arriba , Microtomografía por Rayos XRESUMEN
Surface-enhanced Raman scattering (SERS) substrates based on graphene and its derivatives have recently attracted attention among those interested in the detection of trace molecules; however, these substrates generally show poor uniformity, an unsatisfactory enhancement factor, and require a complex fabrication process. Herein, we design and fabricate three-dimensional (3D) graphene/silicon (3D-Gr/Si) heterojunction SERS substrates to detect various types of molecules. Notably, the detection limit of 3D-Gr/Si can reach 10-10 M for rhodamine 6G (R6G) and rhodamine B (RB), 10-7 M for crystal violet (CRV), copper(II) phthalocyanine (CuPc), and methylene blue (MB), 10-8 M for dopamine (DA), 10-6 M for bovine serum albumin (BSA), and 10-5 M for melamine (Mel), which is superior to most reported graphene-based SERS substrates. Besides, the proposed 3D-Gr/Si heterojunction SERS substrates can achieve a high uniformity with relative standard deviations (RSDs) of less than 5%. Moreover, the 3D-Gr/Si SERS substrates are reusable after washing with ethyl alcohol to remove the adsorbed molecules. These excellent SERS performances are attributed to the novel 3D structure and abundantly exposed atomically thin edges, which facilitate charge transfer between 3D-Gr and probe molecules. We believe that the 3D-Gr/Si heterojunction SERS substrates offer potential for practical applications in biochemical molecule detection and provide insight into the design of high-performance SERS substrates.
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Salmonella typhimurium (S. typhimurium) infection of macrophage induces NLRC4 inflammasome-mediated production of the pro-inflammatory cytokines IL-1ß. Post-translational modifications on NLRC4 are critical for its activation. Sirtuin3 (SIRT3) is the most thoroughly studied mitochondrial nicotinamide adenine dinucleotide (NAD+) -dependent deacetylase. We wondered whether SIRT3 mediated-deacetylation could take part in NLRC4 inflammasome activation. Methods: We initially tested IL-1ß production and pyroptosis after cytosolic transfection of flagellin or S. typhimurium infection in wild type and SIRT3-deficient primary peritoneal macrophages via immunoblotting and ELISA assay. These results were confirmed in SIRT3-deficient immortalized bone marrow derived macrophages (iBMDMs) which were generated by CRISPR-Cas9 technology. In addition, in vivo experiments were conducted to confirm the role of SIRT3 in S. typhimurium-induced cytokines production. Then NLRC4 assembly was analyzed by immune-fluorescence assay and ASC oligomerization assay. Immunoblotting, ELISA and flow cytometry were performed to clarify the role of SIRT3 in NLRP3 and AIM2 inflammasomes activation. To further investigate the mechanism of SIRT3 in NLRC4 activation, co-immunoprecipitation (Co-IP), we did immunoblot, cellular fractionation and in-vitro deacetylation assay. Finally, to clarify the acetylation sites of NLRC4, we performed liquid chromatography-mass spectrometry (LC-MS) and immunoblotting analysis. Results: SIRT3 deficiency led to significantly impaired NLRC4 inflammasome activation and pyroptosis both in vitro and in vivo. Furthermore, SIRT3 promotes NLRC4 inflammasome assembly by inducing more ASC speck formation and ASC oligomerization. However, SIRT3 is dispensable for NLRP3 and AIM2 inflammasome activation. Moreover, SIRT3 interacts with and deacetylates NLRC4 to promote its activation. Finally, we proved that deacetylation of NLRC4 at Lys71 or Lys272 could promote its activation. Conclusions: Our study reveals that SIRT3 mediated-deacetylation of NLRC4 is pivotal for NLRC4 activation and the acetylation switch of NLRC4 may aid the clearance of S. typhimurium infection.
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Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas de Unión al Calcio/metabolismo , Inflamasomas/metabolismo , Sirtuina 3/metabolismo , Acetilación , Secuencia de Aminoácidos , Animales , Proteínas Reguladoras de la Apoptosis/química , Proteínas Reguladoras de la Apoptosis/genética , Sitios de Unión/genética , Proteínas Adaptadoras de Señalización CARD/química , Proteínas Adaptadoras de Señalización CARD/genética , Proteínas Adaptadoras de Señalización CARD/metabolismo , Proteínas de Unión al Calcio/química , Proteínas de Unión al Calcio/genética , Línea Celular , Citocinas/biosíntesis , Femenino , Técnicas de Inactivación de Genes , Células HEK293 , Humanos , Inflamasomas/inmunología , Macrófagos/inmunología , Macrófagos/metabolismo , Macrófagos/microbiología , Masculino , Ratones , Ratones Noqueados , Medicina de Precisión , Salmonella typhimurium/inmunología , Salmonella typhimurium/patogenicidad , Sirtuina 3/deficiencia , Sirtuina 3/genéticaRESUMEN
Intestinal stromal cells are known to modulate the propagation and differentiation of intestinal stem cells1,2. However, the precise cellular and molecular mechanisms by which this diverse stromal cell population maintains tissue homeostasis and repair are poorly understood. Here we describe a subset of intestinal stromal cells, named MAP3K2-regulated intestinal stromal cells (MRISCs), and show that they are the primary cellular source of the WNT agonist R-spondin 1 following intestinal injury in mice. MRISCs, which are epigenetically and transcriptomically distinct from subsets of intestinal stromal cells that have previously been reported3-6, are strategically localized at the bases of colon crypts, and function to maintain LGR5+ intestinal stem cells and protect against acute intestinal damage through enhanced R-spondin 1 production. Mechanistically, this MAP3K2 specific function is mediated by a previously unknown reactive oxygen species (ROS)-MAP3K2-ERK5-KLF2 axis to enhance production of R-spondin 1. Our results identify MRISCs as a key component of an intestinal stem cell niche that specifically depends on MAP3K2 to augment WNT signalling for the regeneration of damaged intestine.
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Mucosa Intestinal/citología , MAP Quinasa Quinasa Quinasa 2/metabolismo , Nicho de Células Madre , Células del Estroma/citología , Animales , Antígenos CD34 , Colitis/patología , Colitis/prevención & control , Epigénesis Genética , Femenino , Mucosa Intestinal/patología , Factores de Transcripción de Tipo Kruppel/metabolismo , Masculino , Ratones , Especies Reactivas de Oxígeno/metabolismo , Tetraspanina 28 , Trombospondinas/biosíntesis , Trombospondinas/metabolismo , Antígenos Thy-1RESUMEN
Intraocular pressure (IOP) is an essential indicator of the diagnosis and treatment of glaucoma. IOP has an apparent physiological rhythm, and it often reaches its peak value at night. To avoid missing the peak value at night and sample the entire rhythm cycle, the continuous monitoring of IOP is urgently needed. A wearable contact lens IOP sensor based on a platinum (Pt) strain gauge is fabricated by the micro-electro-mechanical (MEMS) process. The structure and parameters of the strain gauge are optimized to improve the sensitivity and temperature stability. Tests on an eyeball model indicate that the IOP sensor has a high sensitivity of 289.5 µV/mmHg and excellent dynamic cycling performance at different speeds of IOP variation. The temperature drift coefficient of the sensor is 33.4 µV/°C. The non-invasive IOP sensor proposed in this report exhibits high sensitivity and satisfactory stability, promising a potential in continuous IOP monitoring.
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As the second leading cause of blindness in the world, glaucoma is mainly caused by persistent high intraocular pressure (IOP) that compresses the optic nerve and causes permanent damage. Noninvasive continuous monitoring of IOP is an essential method for the diagnosis and treatment of glaucoma. In this paper, we propose a new strain gauge material based on graphene nanowalls (GNWs) for continuous monitoring of IOP with high sensitivity in a wide range. By simulation, we studied the relationship between the strain of the cornea and contact lens and IOP. The structure and the location of the GNWs in the contact lens are optimized. A method for transferring GNWs on contact lenses with the assistance of a gold film is proposed. The simulated tests on porcine eyes in vitro show that the resistance response of the device to normal IOP fluctuation reaches 1.014 kΩ mmHg-1. Its normal sensitivity of 42 250 ppm mmHg-1 and the response range of 0-75 mmHg are far more than those of most noninvasive methods reported before. This study shows the enormous potential of GNWs for continuous IOP monitoring with high sensitivity and low power consumption.
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Córnea/metabolismo , Grafito/química , Presión Intraocular , Monitoreo Fisiológico/métodos , Nanoestructuras/química , Dispositivos Electrónicos Vestibles , Animales , Lentes de Contacto , Monitoreo Fisiológico/instrumentación , Porcinos , Tonometría Ocular/instrumentación , Tonometría Ocular/métodosRESUMEN
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Three-dimensional graphene (3D-Gr) with excellent light absorption properties has received enormous interest, but in conventional processes to prepare 3D-Gr, amorphous carbon layers are inevitably introduced as buffer layers that may degrade the performance of graphene-based devices. Herein, 3D-Gr is prepared on germanium (Ge) using two-dimensional graphene (2D-Gr) as the buffer layer. 2D-Gr as the buffer layer facilitates the in situ synthesis of 3D-Gr on Ge by plasma-enhanced chemical vapor deposition (PECVD) by promoting 2D-Gr nucleation and reducing the barrier height. The growth mechanism is investigated and described. The enhanced light absorption as confirmed by theoretical calculation and 3D-Gr/2D-Gr/Ge with a Schottky junction improves the performance of optoelectronic devices without requiring pre- and post-transfer processes. The photodetector constructed with 3D-Gr/2D-Gr/Ge shows an excellent responsivity of 1.7 A W-1 and detectivity 3.42 × 1014 cm Hz1/2 W-1 at a wavelength of 1550 nm. This novel hybrid structure that incorporates 3D- and 2D-Gr into Ge-based integrated circuits and photodetectors delivers excellent performance and has large commercial potential.
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The evaluation of intracellular reactive oxygen species (ROS) would greatly deepen the understanding of cell metabolism/proliferation and tumor detection. However, current long-acting level tracking techniques for intracellular ROS remain unsuited to practical applications. To solve this problem, we synthesized cyclotriphosphazene-doped graphene quantum dots (C-GQDs) whose quantum yield is highly sensitive to ROS (increased by 400% from 0.12 to 0.63). Electron cloud polarization of oxidized cyclotriphosphazene rings in C-GQDs is confirmed to account for this novel optical property by density functional theory calculations and experimental results. In combination with excellent biological stability, C-GQDs achieve a long-acting evaluation of intracellular ROS level (more than 72 h) with an accuracy of 98.3%. In addition, recognition rates exceeding 90% are demonstrated to be feasible for eight kinds of tumor cell lines cultured with C-GQDs, which can also be expanded to in vivo detection. C-GQDs also show a high recognition rate (82.33%) and sensitivity (79.65%) for tumor cells in blood samples.
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Grafito/química , Mediciones Luminiscentes/métodos , Neoplasias/metabolismo , Puntos Cuánticos/química , Especies Reactivas de Oxígeno/análisis , Animales , Línea Celular Tumoral , Humanos , Luminiscencia , Mediciones Luminiscentes/instrumentación , Ratones , Ratones Endogámicos BALB C , Neoplasias/diagnóstico , Oxidación-Reducción , Compuestos de Fósforo/química , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The innate immune sensor NLRP3 assembles an inflammasome complex with NEK7 and ASC to activate caspase-1 and drive the maturation of proinflammatory cytokines IL-1ß and IL-18. NLRP3 inflammasome activity must be tightly controlled, as its over-activation is involved in the pathogenesis of inflammatory diseases. Here, we show that NLRP3 inflammasome activation is suppressed by a centrosomal protein Spata2. Spata2 deficiency enhances NLRP3 inflammasome activity both in the macrophages and in an animal model of peritonitis. Mechanistically, Spata2 recruits the deubiquitinase CYLD to the centrosome for deubiquitination of polo-like kinase 4 (PLK4), the master regulator of centrosome duplication. Deubiquitination of PLK4 facilitates its binding to and phosphorylation of NEK7 at Ser204. NEK7 phosphorylation in turn attenuates NEK7 and NLRP3 interaction, which is required for NLRP3 inflammasome activation. Pharmacological or shRNA-mediated inhibition of PLK4, or mutation of the NEK7 Ser204 phosphorylation site, augments NEK7 interaction with NLRP3 and causes increased NLRP3 inflammasome activation. Our study unravels a novel centrosomal regulatory pathway of inflammasome activation and may provide new therapeutic targets for the treatment of NLRP3-associated inflammatory diseases.
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Centrosoma/inmunología , Enzima Desubiquitinante CYLD/metabolismo , Inflamasomas/inmunología , Quinasas Relacionadas con NIMA/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas/fisiología , Animales , Centrosoma/metabolismo , Citocinas/metabolismo , Enzima Desubiquitinante CYLD/genética , Modelos Animales de Enfermedad , Inflamasomas/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Macrófagos/patología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Quinasas Relacionadas con NIMA/genética , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Peritonitis/inmunología , Peritonitis/metabolismo , Peritonitis/patología , Fosforilación , Proteínas Serina-Treonina Quinasas/genética , Transducción de Señal , UbiquitinaciónRESUMEN
With the minimization and higher power of electronic devices, materials with effective heat dissipation and high electrical insulation have attracted relentless interest. Especially, highly thermally conductive, highly electrically insulating but low filler content of polymer-based composites are desirable. Herein, a facile and eco-friendly cotton candy-templated method (CTM) to construct three-dimensional heat transport pathways inside epoxy resin is reported. The fabricated Al2O3/epoxy composites with enhanced heat transport capability feature a 15-fold increase in thermal conductivity at a filler content of 36.2 vol % compared to pristine epoxy. Moreover, the remarkable thermal conductive property has excellent stability over a wide range of temperature before and after heating and cooling cycles. Meanwhile, the CTM composite still retain highly electrical insulation. The cotton candy-templated method proposed in this work is a new avenue for the preparation of three-dimensional heat transport pathways within polymer-based composites for microelectronic packaging and electrical engineering systems.
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Most tissue-resident macrophage (RTM) populations are seeded by waves of embryonic hematopoiesis and are self-maintained independently of a bone marrow contribution during adulthood. A proportion of RTMs, however, is constantly replaced by blood monocytes, and their functions compared to embryonic RTMs remain unclear. The kinetics and extent of the contribution of circulating monocytes to RTM replacement during homeostasis, inflammation, and disease are highly debated. Here, we identified Ms4a3 as a specific gene expressed by granulocyte-monocyte progenitors (GMPs) and subsequently generated Ms4a3TdT reporter, Ms4a3Cre, and Ms4a3CreERT2 fate-mapping models. These models traced efficiently monocytes and granulocytes, but no lymphocytes or tissue dendritic cells. Using these models, we precisely quantified the contribution of monocytes to the RTM pool during homeostasis and inflammation. The unambiguous identification of monocyte-derived cells will permit future studies of their function under any condition.