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1.
Plant Physiol ; 194(3): 1631-1645, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38039102

RESUMEN

PSI is a sophisticated photosynthesis protein complex that fuels the light reaction of photosynthesis in algae and vascular plants. While the structure and function of PSI have been studied extensively, the dynamic regulation on PSI oligomerization and high light response is less understood. In this work, we characterized a high light-responsive immunophilin gene FKB20-2 (FK506-binding protein 20-2) required for PSI oligomerization and high light tolerance in Chlamydomonas (Chlamydomonas reinhardtii). Biochemical assays and 77-K fluorescence measurement showed that loss of FKB20-2 led to the reduced accumulation of PSI core subunits and abnormal oligomerization of PSI complexes and, particularly, reduced PSI intermediate complexes in fkb20-2. It is noteworthy that the abnormal PSI oligomerization was observed in fkb20-2 even under dark and dim light growth conditions. Coimmunoprecipitation, MS, and yeast 2-hybrid assay revealed that FKB20-2 directly interacted with the low molecular weight PSI subunit PsaG, which might be involved in the dynamic regulation of PSI-light-harvesting complex I supercomplexes. Moreover, abnormal PSI oligomerization caused accelerated photodamage to PSII in fkb20-2 under high light stress. Together, we demonstrated that immunophilin FKB20-2 affects PSI oligomerization probably by interacting with PsaG and plays pivotal roles during Chlamydomonas tolerance to high light.


Asunto(s)
Chlamydomonas reinhardtii , Chlamydomonas , Inmunofilinas , Complejo de Proteína del Fotosistema I/genética , Chlamydomonas/genética , Isomerasa de Peptidilprolil , Chlamydomonas reinhardtii/genética
2.
J Vis ; 23(11): 73, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37733505

RESUMEN

During eye growth, scleral development critically determine eye size and thus the refractive status of the eye. Scleral remodeling in myopia includes scleral thinning, loss of scleral tissue, and weakening of the mechanical properties. Therefore, an intervention aiming at stiffening scleral tissues (crosslinking, SCXL) may provide a way to prevent or treat myopia. The development of SCXL requires tools to evaluate the effects of crosslinking on the mechanical properties of tissues, particularly in sclera where the mechanical properties are more spatially heterogeneous than in the cornea, anisotropic, and varying locally from the anterior to posterior regions. Here, we apply the high-frequency OCE technique to measure the heterogeneous mechanical properties of posterior scleral tissues and, evaluate the changes in shear moduli after SCXL. As a model system, we use ex vivo in porcine eyes and riboflavin-assisted UV crosslinking. From measured elastic wave speeds (6-16kHz), the average out-of-plane shear modulus was 0.71±0.12MPa (n=20) for normal scleras. After treatment, the shear modulus increased to 1.50±0.39MPa. This 2-fold change was consistent with the increase of static Young's modulus from 5.5±.1 to 9.3±1.9MPa after crosslinking, using conventional uniaxial extensometry. OCE revealed regional stiffness differences across the temporal, nasal, and deeper posterior sclera, demonstrating its potential as a noninvasive tool to test the effect of scleral crosslinking.


Asunto(s)
Diagnóstico por Imagen de Elasticidad , Miopía , Porcinos , Animales , Esclerótica/diagnóstico por imagen , Miopía/diagnóstico por imagen , Refracción Ocular , Pruebas de Visión
3.
Int J Mol Sci ; 24(21)2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37958835

RESUMEN

Vacuolar sugar transporters transport sugar across the tonoplast, are major players in maintaining sugar homeostasis, and therefore play vital roles in plant growth, development, and biomass yield. In this study, we analyzed the physiological roles of the tonoplast monosaccharide transporter 2 (TMT2) in Arabidopsis. In contrast to the wild type (WT) that produced uniform seedlings, the tmt2 mutant produced three types of offspring: un-germinated seeds (UnG), seedlings that cannot form true leaves (tmt2-S), and seedlings that develop normally (tmt2-L). Sucrose, glucose, and fructose can substantially, but not completely, rescue the abnormal phenotypes of the tmt2 mutant. Abnormal cotyledon development, arrested true leaf development, and abnormal development of shoot apical meristem (SAM) were observed in tmt2-S seedlings. Cotyledons from the WT and tmt2-L seedlings restored the growth of tmt2-S seedlings through micrografting. Moreover, exogenous sugar sustained normal growth of tmt2-S seedlings with cotyledon removed. Finally, we found that the TMT2 deficiency resulted in growth defects, most likely via changing auxin signaling, target of rapamycin (TOR) pathways, and cellular nutrients. This study unveiled the essential functions of TMT2 for seed germination and initial seedling development, ensuring cotyledon function and mobilizing sugars from cotyledons to seedlings. It also expanded the current knowledge on sugar metabolism and signaling. These findings have fundamental implications for enhancing plant biomass production or seed yield in future agriculture.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Carbohidratos , Germinación , Glucosa/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Plantones/metabolismo
4.
J Mech Phys Solids ; 1692022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37828998

RESUMEN

Surface waves play important roles in many fundamental and applied areas from seismic detection to material characterizations. Supershear surface waves with propagation speeds greater than bulk shear waves have recently been reported, but their properties are not well understood. Here we describe theoretical and experimental results on supershear surface waves in rubbery materials. We find that supershear surface waves can be supported in viscoelastic materials with no restriction on the shear quality factor. Interestingly, the effect of prestress on the speed of the supershear surface wave is opposite to that of the Rayleigh surface wave. Furthermore, anisotropy of material affects the supershear wave much more strongly than the Rayleigh surface wave. We offer heuristic interpretation as well as theoretical verification of our experimental observations. Our work points to the potential applications of supershear waves for characterizing the bulk mechanical properties of soft solid from the free surface.

5.
Opt Express ; 29(11): 15980-15994, 2021 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-34154171

RESUMEN

A high-energy, high-beam-quality, high-contrast picosecond optical parametric chirped-pulse amplification (ps-OPCPA) laser system was demonstrated. The pulse from a femtosecond oscillator was stretched to 4 ps, after which it was amplified from 140 pJ to 600 µJ by an 8 ps/6 mJ pump laser in two non-collinear OPCPA stages. The total gain was >106, and the root mean square of the energy stability of the laser system was 1.6% in 10 h. The contrasts of the solid and fiber mode-locked femtosecond oscillator-seeded ps-OPCPA systems were compared, and a signal-to-noise ratio of >1011 was achieved. Using this system, the contrast of the front end in high-power picosecond petawatt laser facility was improved by ∼40 dB to >1011, beyond ∼200 ps ahead of the main pulse with an output level of 60 mJ.

6.
Appl Opt ; 59(20): 6070-6075, 2020 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-32672752

RESUMEN

A high-energy, high-beam-quality, and pulse-width-tunable Nd:YAG laser system, pumped by vertical cavity surface emitting laser arrays and laser diodes, is demonstrated and applied to a velocity interferometry system for any reflector (VISAR) application in a high power laser facility. A multistage multipass amplification structure is used to fully extract the amplifier energy and obtain a high-energy pulse. The temporal waveform is compensated to provide a square waveform, with a flatness less than 8% (peak-to-peak value). The peak power is greater than 100 kW with a frequency-doubling efficiency of 25% for a 50 ns pulse width. The laser operates as a single shot with 1-5 Hz repetition frequency and 0.7% rms energy stability.

7.
J Acoust Soc Am ; 148(6): 3963, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33379903

RESUMEN

Measuring stress levels in loaded structures is crucial to assess and monitor structure health and to predict the length of remaining structural life. Many ultrasonic methods are able to accurately predict in-plane stresses inside a controlled laboratory environment but struggle to be robust outside, in a real-world setting. That is because these methods rely either on knowing beforehand the material constants (which are difficult to acquire) or require significant calibration for each specimen. This paper presents an ultrasonic method to evaluate the in-plane stress in situ directly, without knowing any material constants. The method is simple in principle, as it only requires measuring the speed of two angled shear waves. It is based on a formula that is exact for incompressible solids, such as soft gels or tissues, and is approximately true for compressible "hard" solids, such as steel and other metals. The formula is validated by finite element simulations, showing that it displays excellent accuracy, with a small error on the order of 1%.

8.
J Insect Sci ; 20(6)2020 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-33180944

RESUMEN

Rice leaffolders are important pests on rice in Asia, Oceania, and Africa, causing serious loss to rice production. There are two main rice leaffolders in China, namely Cnaphalocrocis medinalis (Guenée) and C. exigua (Butler) with the former having the ability of long-distance migration. To reveal the differences in the mitochondrial genomes (mitogenome) between them, we compared the completed mitogenome of C. exigua with three C. medinalis individuals. Although phylogenetic analysis based on the mitogenomic data strongly supported the close relationship between these two species, many differences were still being revealed. The results showed that the mitogenome of C. exigua was shorter in length (15,262 bp) and slight lower in AT content than that of C. medinalis. Except for the different start codons of nad3 and nad6 gene, we also found the cox1 gene had a typical start codon 'ATG' which suggested that the starting position of this gene must be reconsidered in the entire superfamily Pyraloidea. All tRNAs have a typical clover-leaf structure, except for the dihydrouridine (DHU) stem losing of trnS1, which has the atypical anticondon 'TCT' instead of 'GCT' in C. medinalis and most Pyraloidea species. Two intergenic regions (between trnY and cox1, nad3 and trnA) featured by AT repeats were only found in C. medinalis and even rarely appeared in reported Pyraloidea species. Furthermore, regardless of interspecific comparison or intraspecific comparison of these two species, protein coding genes, especially the atp8 genes, had quite different evolutionary rates.


Asunto(s)
Genoma de los Insectos , Genoma Mitocondrial , Mariposas Nocturnas/genética , Animales , Secuencia de Bases , Filogenia
9.
Philos Trans A Math Phys Eng Sci ; 377(2144): 20180075, 2019 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-30879421

RESUMEN

Functionally graded soft materials (FGSMs) with microstructures and mechanical properties exhibiting gradients across a spatial volume to satisfy specific functions have received interests in recent years. How to characterize the mechanical properties of these FGSMs in vivo/in situ and/or in a non-destructive manner is a great challenge. This paper investigates the use of ultrasound elastography in the mechanical characterization of FGSMs. An efficient finite-element model was built to calculate the dispersion relation for surface waves in FGSMs. For FGSMs with large elastic gradients, the measured dispersion relation can be used to identify mechanical parameters. In the case where the elastic gradient is smaller than a certain critical value calculated here, our analysis on transient wave motion in FGSMs shows that the group velocities measured at different depths can infer the local mechanical properties. Experiments have been performed on polyvinyl alcohol (PVA) cryogel to demonstrate the usefulness of the method. Our analysis and the results may not only find broad applications in mechanical characterization of FGSMs but also facilitate the use of shear wave elastography in clinics because many diseases change the local elastic properties of soft tissues and lead to different material gradients. This article is part of the theme issue 'Rivlin's legacy in continuum mechanics and applied mathematics'.

10.
Toxicol Ind Health ; 35(2): 109-118, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30558485

RESUMEN

Cigarette smoking is an established risk factor for some oral diseases. As an essential fluid in the oral cavity, saliva is crucial to maintain oral health. Relative to active smoking, there are very few studies assessing the effect of passive smoking on salivary cytokines levels. In the present study, we established the rat models by the means of the intraoral cigarette smoking or whole body cigarette smoke exposure to simulate human active or passive smoking, respectively. The effects of active or passive smoking on salivary cytokines levels were assessed by using ProcartaPlex multiplex immunoassays. The results of the current study indicated that both active and passive smoking diminished the body weights of rats and increased the levels of some blood counts. Intriguingly, active smoking enhanced the salivary levels of IL-6 and IL-12 p70 and passive smoking elevated the salivary IL-6 level. Moreover, active smoking appeared to have a more prominent activation effect on the salivary IL-6 level. It was noted that active or passive smoking had no significant effect on the salivary IFN-γ level. Active or passive smoking could have potential effects on the salivary levels of some pro-inflammatory cytokines.


Asunto(s)
Citocinas/análisis , Saliva/química , Fumar/fisiopatología , Contaminación por Humo de Tabaco/análisis , Animales , Peso Corporal , Femenino , Interleucina-6/análisis , Masculino , Proyectos Piloto , Ratas , Ratas Wistar
11.
Clin Chem Lab Med ; 55(1): 38-46, 2017 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-27362960

RESUMEN

BACKGROUND: The long noncoding RNAs (lncRNAs) have gradually been reported to be an important class of RNAs with pivotal roles in regulation of gene expression, and thus are involved in multitudinous human complex diseases. However, the biological functions and precise mechanisms of the majority of lncRNAs are still poorly understood. METHODS: In the study, we tested genomic variations in lncRNA-metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) loci, and their potentially functional correlationship with pulmonary arterial hypertension (PAH) susceptibility based on a case-control study with a total of 587 PAH patients and 736 healthy controls in southern Chinese. RESULTS: We found that the rs619586A>G single nucleotide polymorphism (SNP) was significantly associated with PAH risk. The carriers with G variant genotypes had a decreased risk of PAH (odds ratio [OR]=0.69, 95% confidence interval [CI]=0.53-0.90, p=0.007) compared to the rs619586AA genotype. Further functional experiments indicated that the alteration from rs619586A to G in MALAT1 could directly upregulate X box-binding protein 1 (XBP1) expression via functioning as the competing endogenous RNA (ceRNA) for miR-214, and consequentially inhibiting the vascular endothelial cells proliferation and migration in vitro by shortening S-M phase transition. CONCLUSIONS: Taken together, our findings propose that functional polymorphism rs619586A>G in MALAT1 gene plays an important role in PAH pathogenesis and may serve as a potential indicator for PAH susceptibility.


Asunto(s)
Pueblo Asiatico/genética , Hipertensión Pulmonar/genética , Polimorfismo de Nucleótido Simple/genética , ARN Largo no Codificante/genética , Proliferación Celular , China , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Hipertensión Pulmonar/metabolismo , Masculino , Persona de Mediana Edad , ARN Largo no Codificante/metabolismo
12.
J Acoust Soc Am ; 142(3): 1526, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28964064

RESUMEN

Determining the mechanical properties of soft biological tissues can be of great importance. For example, the microstructures of many soft tissues, such as those of the human Achilles tendon, have been identified as typical anisotropic materials. This paper proposes an inverse approach that uses guided wave elastography to determine the anisotropic elastic and hyperelastic parameters of thin-walled transversely isotropic biological soft tissues. This approach was developed from the theoretical solutions for the dispersion relations of guided waves, which were derived based on a constitutive model suitable for describing the deformation behavior of such tissues. The properties of these solutions were investigated; in particular, sensitivity to data errors was addressed by introducing the concept of the condition number. To further validate the proposed inverse approach, the guided wave elastography of thin-walled transversely isotropic soft tissues was investigated using numerical experiments. The results indicated that the four constitutive parameters (other than the tensile modulus along the direction of the fibers, EL) could be determined with a good level of accuracy using this method.

13.
Soft Matter ; 12(18): 4204-13, 2016 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-27074161

RESUMEN

Compression of a film/substrate bilayer system with different surface/interfacial structures can lead to diverse buckling patterns including sinusoidal wrinkles, ridges, folds, creases and tilted sawteeth wrinkles. In this paper, we show that elastic wave band gaps in the film/substrate bilayer system largely depend on the wrinkling patterns. More interestingly, we find that different wrinkling patterns investigated here can coexist and evolve in one bilayer system and the elastic wave propagation behaviors can be controlled by manipulating the hybrid wrinkling patterns. Our analysis also reveals that the periodic stress pattern plays a dominant role in tuning the bandgap structures in comparison to geometrical patterns caused by surface instability. A careful investigation of the transmission spectra of the composite systems has validated the main findings given by the analysis based on the Bloch wave theory. Potential use of the method and materials reported here to gain wide attenuation frequency ranges and the design of nesting Fibonacci superlattices have been demonstrated.

14.
Acta Biomater ; 175: 114-122, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38101555

RESUMEN

Understanding corneal stiffness is valuable for improving refractive surgery, detecting corneal abnormalities, and assessing intraocular pressure. However, accurately measuring the elastic properties, specifically the tensile and shear moduli that govern mechanical deformation, has been challenging. To tackle this issue, we have developed guided-wave optical coherence elastography that can simultaneously excite and analyze symmetric (S0) and anti-symmetric (A0) elastic waves in the cornea at around 10 kHz frequencies, enabling us to extract tensile and shear properties from measured wave dispersion curves. We verified the technique using elastomer phantoms and ex vivo porcine corneas and investigated the dependence on intraocular pressure using acoustoelastic theory that incorporates corneal tension and a nonlinear constitutive tissue model. In a pilot study involving six healthy human subjects aged 31 to 62, we measured shear moduli (Gzx) of 94±20 kPa (mean±standard deviation) and tensile moduli (Exx) of 4.0±1.1 MPa at central corneas. Our preliminary analysis of age-dependence revealed contrasting trends: -8.3±4.5 kPa/decade for shear and 0.30±0.21 MPa/decade for tensile modulus. This OCE technique has the potential to become a highly useful clinical tool for the quantitative biomechanical assessment of the cornea. STATEMENT OF SIGNIFICANCE: This article reports an innovative elastography technique using two guided elastic waves, demonstrating the measurement of both tensile and shear moduli in human cornea in vivo with unprecedented precision. This technique paves the way for comprehensive investigations into corneal mechanics and holds clinical significance in various aspects of corneal health and disease management.


Asunto(s)
Diagnóstico por Imagen de Elasticidad , Humanos , Animales , Porcinos , Módulo de Elasticidad , Proyectos Piloto , Presión Intraocular , Córnea/diagnóstico por imagen
15.
J Biomech ; 174: 112279, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39146898

RESUMEN

In vivo mechanical characterization of skin finds broad applications in understanding skin aging, diagnosis of some skin diseases and assessing the effectiveness of diverse skin care strategies. Skin has a layered structure consisting of the epidermis, dermis and subcutaneous layers. Although much effort has been made towards mechanical characterization of skin, it remains a challenging issue to measure the mechanical properties of an individual layer in vivo. To address this issue, we here report a guided wave elastography method for layered human skin which incorporates the effect of muscle states. Both finite element simulations and phantom experiments have been performed to validate the method. For skin-mimicking phantoms with different fat layer thicknesses, the errors in the identified shear modulus of the skin layers are no more than 11 %. In vivo experiments have been carried out on 6 healthy subjects to demonstrate the potential use of the method in clinics. A statistical analysis indicates the muscle contraction contributes to the stiffening of the skin (p < 0.001). Finally, a phase diagram has been constructed to reveal the extent to which muscle sates (including both passive and active states) affect the measurement of elastic modulus of a skin layer, which may guide the application of the method in practice.

16.
IEEE Trans Med Imaging ; 43(4): 1434-1448, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38032772

RESUMEN

Shear wave elastography (SWE) enables the measurement of elastic properties of soft materials in a non-invasive manner and finds broad applications in various disciplines. The state-of-the-art SWE methods rely on the measurement of local shear wave speeds to infer material parameters and suffer from wave diffraction when applied to soft materials with strong heterogeneity. In the present study, we overcome this challenge by proposing a physics-informed neural network (PINN)-based SWE (SWENet) method. The spatial variation of elastic properties of inhomogeneous materials has been introduced in the governing equations, which are encoded in SWENet as loss functions. Snapshots of wave motions have been used to train neural networks, and during this course, the elastic properties within a region of interest illuminated by shear waves are inferred simultaneously. We performed finite element simulations, tissue-mimicking phantom experiments, and ex vivo experiments to validate the method. Our results show that the shear moduli of soft composites consisting of matrix and inclusions of several millimeters in cross-section dimensions with either regular or irregular geometries can be identified with excellent accuracy. The advantages of the SWENet over conventional SWE methods consist of using more features of the wave motions and enabling seamless integration of multi-source data in the inverse analysis. Given the advantages of SWENet, it may find broad applications where full wave fields get involved to infer heterogeneous mechanical properties, such as identifying small solid tumors with ultrasound SWE, and differentiating gray and white matters of the brain with magnetic resonance elastography.


Asunto(s)
Diagnóstico por Imagen de Elasticidad , Diagnóstico por Imagen de Elasticidad/métodos , Ultrasonografía , Física , Redes Neurales de la Computación , Encéfalo
17.
Int Immunopharmacol ; 131: 111915, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38522141

RESUMEN

The aberrant activation of NLRP3 inflammasome contributes to pathogenesis of multiple inflammation-driven human diseases. However, the medications targeting NLRP3 inflammasome are not approved for clinic use to date. Here, we show that ascorbyl palmitate (AP), a lipophilic derivative of ascorbic acid (AA) and a safe food additive, is a potent inhibitor of NLRP3 inflammasome. Compared with AA, AP inhibited the activation of NLRP3 inflammasome with increased potency and specificity. Mechanistically, AP directly scavenged mitochondrial reactive oxygen species (mitoROS) by its antioxidant activity and blocked NLRP3-NEK7 interaction and NLRP3 inflammasome assembly. Moreover, AP showed more significant preventive effects than AA in LPS-induced systemic inflammation, dextran sulfate sodium (DSS)-induced colitis and experimental autoimmune encephalomyelitis (EAE). Thus, our results suggest that AP is a potential therapeutic combating NLRP3-driven diseases.


Asunto(s)
Ácido Ascórbico/análogos & derivados , Colitis , Inflamasomas , Humanos , Animales , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Ácido Ascórbico/farmacología , Ácido Ascórbico/uso terapéutico , Inflamación/tratamiento farmacológico , Ratones Endogámicos C57BL , Sulfato de Dextran
18.
Biomater Res ; 28: 0044, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38952715

RESUMEN

Accurate measurement of gingiva's biomechanical properties in vivo has been an active field of research but remained an unmet challenge. Currently, there are no noninvasive tools that can accurately quantify tensile and shear moduli, which govern gingival health, with sufficiently high accuracy. This study presents the application of high-frequency optical coherence elastography (OCE) for characterizing gingival tissue in both porcine models and human subjects. Dynamic mechanical analysis, histology studies, and strain analysis are performed to support the OCE result. Our findings demonstrate substantial differences in tissue stiffness between supra-dental and inter-dental gingiva, validated by dynamic mechanical analysis and OCE. We confirmed the viscoelastic, nearly linear, and transverse-isotropic properties of gingiva in situ, establishing the reliability of OCE measurements. Further, we investigated the effects of tissue hydration, collagen degradation, and dehydration on gingival stiffness. These conditions showed a decrease and increase in stiffness, respectively. While preliminary, our study suggests OCE's potential in periodontal diagnosis and oral tissue engineering, offering real-time, millimeter-scale resolution assessments of tissue stiffness, crucial for clinical applications and biomaterial optimization in reconstructive surgeries.

19.
Cell Mol Immunol ; 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39030423

RESUMEN

Sterile neuroinflammation is a major driver of multiple neurological diseases. Myelin debris can act as an inflammatory stimulus to promote inflammation and pathologies, but the mechanism is poorly understood. Here, we showed that lysophosphatidylserine (LysoPS)-GPR34 axis played a critical role in microglia-mediated myelin debris sensing and the subsequent neuroinflammation. Myelin debris-induced microglia activation and proinflammatory cytokine expression relied on its lipid component LysoPS. Both myelin debris and LysoPS promoted microglia activation and the production of proinflammatory cytokines via GPR34 and its downstream PI3K-AKT and ERK signaling. In vivo, reducing the content of LysoPS in myelin or inhibition of GPR34 with genetic or pharmacological approaches reduced neuroinflammation and pathologies in the mouse models of multiple sclerosis and stroke. Thus, our results identify GPR34 as a key receptor to sense demyelination and CNS damage and promote neuroinflammation, and suggest it as a potential therapeutic target for demyelination-associated diseases.

20.
IEEE Trans Biomed Eng ; PP2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38032780

RESUMEN

OBJECTIVE: The mechanical properties of corneal tissues play a crucial role in determining corneal shape and have significant implications in vision care. This study aimed to address the challenge of obtaining accurate in vivo data for the human cornea. METHODS: We have developed a high-frequency optical coherence elastography (OCE) technique using shear-like antisymmetric (A0)-mode Lamb waves at frequencies above 10 kHz. RESULTS: By incorporating an anisotropic, nonlinear constitutive model and utilizing the acoustoelastic theory, we gained quantitative insights into the influence of corneal tension on wave speeds and elastic moduli. Our study revealed significant spatial variations in the shear modulus of the corneal stroma on healthy subjects for the first time. Over an age span from 21 to 34 (N = 6), the central corneas exhibited a mean shear modulus of 87 kPa, while the corneal periphery showed a significant decrease to 44 kPa. The central cornea's shear modulus decreases with age with a slope of -19 +/- 8 kPa per decade, whereas the periphery showed non-significant age dependence. The limbus demonstrated an increased shear modulus exceeding 100 kPa. We obtained wave displacement profiles that are consistent with highly anisotropic corneal tissues. CONCLUSION: Our approach enabled precise measurement of corneal tissue elastic moduli in situ with high precision (< 7%) and high spatial resolution (< 1 mm). Our results revealed significant stiffness variation from the central to peripheral corneas. SIGNIFICANCE: The high-frequency OCE technique holds promise for biomechanical evaluation in clinical settings, providing valuable information for refractive surgeries, degenerative disorder diagnoses, and intraocular pressure assessments.

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