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Elliptical shape microfiber enables many higher order modes compared with a circular microfiber. The small difference in the optical path length among many modes enabled multi-resonance peaks with high contrast in Mach-Zehnder (MZI) interferometers, which allows a large dynamic range and minimum detection sensitivity for broadband ultrasound sensing. In this paper, we present the design and fabrication of an ultra-compact elliptical-silica microfiber utilizing off-axis flame-drawing for ultrasound detection. The narrow transmission peak showed high contrast for ultrasensitive ultrasound wave detection. With a major-axis diameter of 6.25â µm, the elliptical-silica microfiber sensor exhibits a broadband ultrasound frequency response spanning from 20â kHz to 38.5â MHz. Furthermore, it achieves a signal-to-noise ratio (SNR) of up to 80â dB at 1â MHz, which is the resonance frequency of the microfiber and the linear response under driving voltages of 3-10â V for the PZT ultrasound generator. This low-cost microfiber sensor offers exceptional sensitivity across a broad ultrasonic bandwidth response, making it an ideal choice for nondestructive testing (NDT) and medical imaging applications. Its compact size and immunity to electric and magnetic fields further enhance its utility in various environments.
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BACKGROUND: Tar is the main toxic of cigarettes, and its effect on atherosclerosis progression and the underlying mechanisms remain largely unknown. Vascular smooth muscle cells (VSMCs) play a key role in atherogenesis and plaque vulnerability. The present study sought to investigate the mechanism of atherosclerosis progression through tar-induced VSMC necroptosis, a recently described form of necrosis. METHODS: The effect of tar on atherosclerosis progression and VSMC necroptosis was examined in ApoE-/- mice and cultured VSMCs. The role of necroptosis in tar-induced plaque development was evaluated in RIPK3-deletion mice (ApoE-/-RIPK3-/-). The key proteins of necroptosis in carotid plaques of smokers and non-smokers were also examined. Quantitative proteomics of mice aortas was conducted to further investigate the underlying mechanism. Pharmacological approaches were then applied to modulate the expression of targets to verify the regulatory process of tar-induced necroptosis. RESULTS: Tar administration led to increased atherosclerotic plaque area and reduced collagen and VSMCs in ApoE-/- mice. The expression of RIPK1ãRIPK3ãand MLKL in VSMCs of plaques were all increased in tar-exposed mice and smokers. RIPK3 deletion protected against VSMC loss and plaque progression stimulated by tar. In mechanistic studies, quantitative proteomics analysis of ApoE-/- mice aortas suggested that tar triggered endoplasmic reticulum (ER) stress. PERK-eIF2α-CHOP axis was activated in tar-treated VSMCs and atherosclerotic plaque. Inhibition of ER stress using 4PBA significantly reduced plaque progression and VSMC necroptosis. Further study revealed that ER stress resulted in calcium (Ca2+) release into mitochondria and cytoplasm. Elevated Ca2+ levels lead to mitochondrial dysfunction and excessive reactive oxygen species (ROS) production, which consequently promote RIPK3-dependent necroptosis. In addition, Ca2+/calmodulin-dependent protein kinase II (CaMKII) activated by cytosolic Ca2+ overload binds to RIPK3, accounting for necroptosis. CONCLUSION: The findings revealed that cigarette tar promoted atherosclerosis progression by inducing RIPK3-dependent VSMC necroptosis and identified novel avenues of ER stress and Ca2+ overload.
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Aterosclerose , Placa Aterosclerótica , Alcatrões , Camundongos , Animais , Placa Aterosclerótica/metabolismo , Músculo Liso Vascular , Necroptose , Aterosclerose/metabolismo , Estresse do Retículo Endoplasmático , Apolipoproteínas E/metabolismo , Miócitos de Músculo Liso/metabolismoRESUMO
Aims: Stress hyperglycemia ratio (SHR), an emerging indicator of critical illness, exhibits a significant association with adverse cardiovascular outcomes. The primary aim of this research endeavor is to evaluate the association between fasting SHR and contrast-induced acute kidney injury (CI-AKI). Methods: This cross-sectional study comprised 3,137 patients who underwent coronary angiography (CAG) or percutaneous coronary intervention (PCI). The calculation of fasting SHR involved dividing the admission fasting blood glucose by the estimated mean glucose obtained from glycosylated hemoglobin. CI-AKI was assessed based on elevated serum creatinine (Scr) levels. To investigate the relationship between fasting SHR and the proportion of SCr elevation, piecewise linear regression analysis was conducted. Modified Poisson's regression analysis was implemented to evaluate the correlation between fasting SHR and CI-AKI. Subgroup analysis and sensitivity analysis were conducted to explore result stability. Results: Among the total population, 482 (15.4%) patients experienced CI-AKI. Piecewise linear regression analysis revealed significant associations between the proportion of SCr elevation and fasting SHR on both sides (≤ 0.8 and > 0.8) [ß = -12.651, 95% CI (-23.281 to -2.022), P = 0.020; ß = 8.274, 95% CI (4.176 to 12.372), P < 0.001]. The Modified Poisson's regression analysis demonstrated a statistically significant correlation between both the lowest and highest levels of fasting SHR and an increased incidence of CI-AKI [(SHR < 0.7 vs. 0.7 ≤ SHR < 0.9) ß = 1.828, 95% CI (1.345 to 2.486), P < 0.001; (SHR ≥ 1.3 vs. 0.7 ≤ SHR < 0.9) ß = 2.896, 95% CI (2.087 to 4.019), P < 0.001], which was further validated through subgroup and sensitivity analyses. Conclusion: In populations undergoing CAG or PCI, both lowest and highest levels of fasting SHR were significantly associated with an increased occurrence of CI-AKI.
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Injúria Renal Aguda , Hiperglicemia , Intervenção Coronária Percutânea , Humanos , Angiografia Coronária/efeitos adversos , Estudos Transversais , Meios de Contraste/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Fatores de Risco , Resultado do Tratamento , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Jejum , Hiperglicemia/complicaçõesRESUMO
Synchronously pumped optical parametric oscillators (OPOs) provide ultra-fast light pulses at tuneable wavelengths. Their primary drawback is the need for precise cavity control (temperature and length), with flexibility issues such as fixed repetition rates and marginally tuneable pulse widths. Targeting a simpler and versatile OPO, we explore the inherent disorder of the refractive index in single-mode fibres realising the first random OPO - the parametric analogous of random lasers. This novel approach uses modulation instability (χ(3) non-linearity) for parametric amplification and Rayleigh scattering for feedback. The pulsed system exhibits high inter-pulse coherence (coherence time of ~0.4 ms), offering adjustable repetition rates (16.6-2000 kHz) and pulse widths (0.69-47.9 ns). Moreover, it operates continuously without temperature control loops, resulting in a robust and flexible device, which would find direct application in LiDAR technology. This work sets the stage for future random OPOs using different parametric amplification mechanisms.
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Pyroptosis plays an important role in inflammatory diseases such as viral hepatitis and atherosclerosis. Apigenin exhibits various bioactivities, particularly anti-inflammation, but its effect on pyroptosis remains unclear. The aim of this study is to investigate the effect of apigenin on pyroptosis and explore its potential against inflammatory diseases. THP-1 macrophages treated by lipopolysaccharides/adenosine 5'-triphosphate were used as the in vitro pyroptosis model. Western blot was used to detect the expression of NLRP3 inflammasome components and key regulators. Immunofluorescence was used to observe ROS production and intracellular location of p65. The potential of apigenin against inflammatory diseases was evaluated using atherosclerotic mice. Plaque progression was observed by pathological staining. Immunofluorescence was used to observe the expression of NLRP3 inflammasome components in plaques. The results showed that apigenin inhibited NLRP3 inflammasome activation. Apigenin reduced ROS overproduction and inhibited p65 nuclear translocation. Additionally, apigenin decreased the expression of NLRP3 inflammasome components in the plaque. Plaque progression was inhibited by apigenin. In conclusion, apigenin exhibited a preventive effect on macrophage pyroptosis by reducing oxidative stress and inhibiting the NF-κB pathway. Apigenin may alleviate atherosclerosis at least partially by inhibiting macrophage pyroptosis. These findings suggest apigenin to be a promising therapeutic agent for inflammatory diseases.
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Aterosclerose , NF-kappa B , Camundongos , Animais , NF-kappa B/metabolismo , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose/fisiologia , Apigenina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Estresse Oxidativo/fisiologia , Macrófagos , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismoRESUMO
OBJECTIVE: Plaque erosion (PE) and plaque rupture (PR) are the main subtypes of ST-segment elevation myocardial infarction (STEMI), the differences of metabolic patterns between PE and PR remain largely unknown. METHODS: 132 STEMI patients were divided into training set (PR, n = 36; PE, n = 36) and test set (PR, n = 30; PE, n = 30), the plasma from patients were analyzed by liquid chromatography quadruple time-of-flight mass spectrometry. RESULTS: We identified 56 and 28 differences in training and test set, respectively. Among these metabolites, it was found that docosahexaenoic acid (DHA), salicylic acid and proline were recognized in both tests. Receiver Operating Characteristic (ROC) analysis showed that the area under curve of docosahexaenoic acid (DHA) was 0.81 and 0.75 in training and test samples, respectively; proline was 0.67 and 0.74 in training and test samples, respectively; salicylic acid was 0.70 and 0.73 in training and test samples, respectively. CONCLUSIONS: DHA, salicylic acid, and proline could be used as non-invasive biomarkers to differentiate PE and PR.
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Doença da Artéria Coronariana , Placa Aterosclerótica , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Ácidos Docosa-Hexaenoicos , Angiografia Coronária/métodos , Estudos Retrospectivos , Ruptura Espontânea , Placa Aterosclerótica/diagnóstico , Biomarcadores , Metabolômica , Tomografia de Coerência Óptica/métodosRESUMO
BACKGROUND: Elevated plasma homocysteine levels, known as hyperhomocysteinemia, have been identified as an independent risk factor for atherosclerosis and related cardiovascular diseases. Macrophage pyroptosis-mediated inflammation is crucial in the development of atherosclerosis, but the underlying mechanisms remain unclear. METHODS: A hyperhomocysteinemia atherosclerotic model with ApoE-/- mice fed with a high-methionine diet was constructed to investigate the role of plasma homocysteine in atherosclerosis. THP-1-derived macrophages were used to investigate the mechanisms by which Hcy regulates pyroptosis. RESULTS: We found that hyperhomocysteinemia resulted in larger atherosclerotic plaques and more secretion of inflammatory cytokines, while these effects were attenuated in Caspase-1 knockdown mice. Likewise, in vitro experiments demonstrated that treatment of macrophages with homocysteine resulted in NLRP3 inflammasome activation and pyroptosis, as evidenced by cleavage of Caspase-1, production of downstream IL-1ß, elevation of lactate dehydrogenase activity, and extensive propidium iodide-positive staining of cells. These were all inhibited by Caspase-1 inhibitor. In addition, excessive generation of reactive oxygen species was associated with mitochondrial dysfunction, characterized by loss of mitochondrial membrane potential and ATP synthesis. Moreover, further experiments revealed that homocysteine induced endoplasmic reticulum stress, enhanced communication between the endoplasmic reticulum and mitochondria, and consequently contributed to calcium disorder. Furthermore, the endoplasmic reticulum stress inhibitor, 4PBA, the calcium chelator, BAPTA, and calcium channel inhibitor, 2-APB significantly improved macrophage pyroptosis. CONCLUSION: Homocysteine accelerates atherosclerosis progression by enhancing macrophages pyroptosis via promoting endoplasmic reticulum stress, endoplasmic reticulum-mitochondria coupling, and disturbing of calcium disorder.
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Aterosclerose , Hiper-Homocisteinemia , Animais , Camundongos , Piroptose , Cálcio , Caspase 1 , Estresse do Retículo EndoplasmáticoRESUMO
A novel multi-wavelength Brillouin random fiber laser with the channel space of triple Brillouin frequency shift and high polarization orthogonality between adjacent wavelengths (TOP-MWBRFL), to the best of our knowledge, is experimentally demonstrated. The TOP-MWBRFL is structured in a ring form by cascading two Brillouin random cavities of single-mode fiber (SMF) and one Brillouin random cavity of polarization-maintaining fiber (PMF). Based on polarization pulling properties of stimulated Brillouin scattering in long-distance SMFs and PMFs, the states of polarization (SOPs) of lasing light from SMF random cavities are linearly bounded to the SOPs of local pump light, whereas the SOP of lasing light from the PMF random cavity is strictly clamped on one of the principal axes of the PMF. Thus, the TOP-MWBRFL can stably emit multi-wavelength light with high polarization extinction ratio (>35d B) between adjacent wavelengths without precise polarization feedback. In addition, the TOP-MWBRFL can also work in one polarization mode to stably lase multi-wavelength light with SOP uniformity as high as 37 dB.
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Oxidative stress and lipid metabolism disorder caused by estrogen deficiency are regarded as the main causes of postmenopausal atherosclerosis, but the underlying mechanisms remain still unclear. In this study, ovariectomized (OVX) female ApoE-/- mice fed with high-fat diet were used to imitate postmenopausal atherosclerosis. The atherosclerosis progression was significantly accelerated in OVX mice, accompanied by the upregulation of ferroptosis indicators, including increased lipid peroxidation and iron deposition in the plaque and the plasma. While both estradiol (E2) and ferroptosis inhibitor ferrostatin-1 alleviated atherosclerosis in OVX mice, with the inhibition of lipid peroxidation and iron deposition, as well as the upregulation of xCT and GPX4, especially in endothelial cells. We further investigated the effects of E2 on ferroptosis in endothelial cells induced by oxidized-low-density lipoprotein or ferroptosis inducer Erastin. It was found that E2 exhibited anti-ferroptosis effect through antioxidative functions, including improving mitochondrial dysfunction and upregulating GPX4 expression. Mechanistically, NRF2 inhibition attenuated the effect of E2 against ferroptosis as well as the upregulation of GPX4. Our findings revealed that endothelial cell ferroptosis played a pivotal role in postmenopausal atherosclerosis progression, and the NRF2/GPX4 pathway activation contributed to the protection of E2 against endothelial cell ferroptosis.
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Aterosclerose , Fator 2 Relacionado a NF-E2 , Animais , Feminino , Camundongos , Células Endoteliais , Estrogênios/deficiência , Ferro , Pós-MenopausaRESUMO
We demonstrate a self-injection locking (SIL) in an Er-doped random fiber laser by a high quality factor (high-Q) random fiber grating ring (RFGR) resonator, which enables a single-mode narrow-linewidth lasing with ultra-low intensity and frequency noise. The RFGR resonator includes a fiber ring with a random fiber grating to provide random feedback modes and noise suppression filters with self-adjusted peak frequency adaptable to small perturbations allowing single longitudinal mode over 7000 s with frequency jitter below 3.0 kHz. Single-mode operation is accomplished by carefully controlling phase delays and mode coupling of resonant modes between main ring and RFGR with a side-mode suppression ratio of 70 dB and narrow linewidth of 1.23 kHz. The relative intensity noise is -140 dB/Hz above 100 kHz and the frequency noise is 1 Hz/Hz1/2 above 10 kHz.
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Despite the known promotional effects of cigarette smoking on progression of atherosclerosis (AS), tar as the most dominant toxic component in cigarette smoking has been little studied. Understanding the potential role and mechanisms of tar in AS may be a prerequisite for future reductions in cardiovascular morbidity and mortality. Male ApoE-/- mice were fed with high-fat diet and injected intraperitoneally with cigarette tar (40 mg/kg/day) for 16 weeks. The results showed that cigarette tar significantly promoted the formation of lipid-rich plaques with larger necrotic cores and less fibrous, and caused severe iron overload and lipid peroxidation in AS lesions. Moreover, tar significantly upregulated the expression of hepcidin and downregulated FPN and SLC7A11 of macrophages in AS plaques. Ferroptosis inhibitor (FER-1 and DFO) treatment, hepcidin-knockdown or SLC7A11-overexpression reversed above changes, thereby delaying the progression of atherosclerosis. In vitro, the use of FER-1, DFO, si-hepcidin, and ov-SLC7A11 increased cell viability and inhibited iron accumulation, lipid peroxidation and GSH depletion in tar treated macrophages. These interventions also inhibited the tar induced upregulation of hepcidin, and increased the expression of FPN, SLC7A11, and GPX4. Furthermore, NF-κB inhibitor reversed the regulatory effect of tar on hepcidin/FPN/SLC7A11 axis, and then inhibiting macrophage ferroptosis. These findings indicated that cigarette tar promotes atherosclerosis progression by inducing macrophage ferroptosis via NF-κB-activated hepcidin/FPN/SLC7A11 pathway.
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Aterosclerose , Ferroptose , Placa Aterosclerótica , Masculino , Animais , Camundongos , NF-kappa B/genética , Hepcidinas/genética , Aterosclerose/genética , Transdução de Sinais , MacrófagosRESUMO
In this paper, acoustic, dynamic and static strain variations along a steel I-beam generated by an impact load are reconstructed simultaneously within a single measurement. Based on the chirped pulse φ-OTDR system with the single-shot measurement technique, both a higher strain-sensing resolution and a higher measurable vibration frequency are achieved. In addition, a weak fiber Bragg gratings array (WFBGA) with enhanced Rayleigh reflection is employed as a sensor, providing high signal-to-noise ratio Rayleigh traces, resulting in lower measurement uncertainty. In the experiments, the damping constant and fundamental frequency of the damped harmonic oscillator could then be measured based on the recovered strain variation profile for further structural health analysis. Compared with commercial strain gauges, linear potentiometers, and OFDR systems, the proposed sensing system ensures a distributed, quantitative, and high-frequency sensing ability, with an extensive range of potential applications.
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BACKGROUND: Myocardial infarction with nonobstructive coronary artery (MINOCA) is a heterogeneous syndrome caused by different pathophysiologic mechanisms. There is limited evidence regarding prognosis of patients with MINOCA caused by different mechanisms. OBJECTIVES: The present study aimed to assess the underlying mechanisms of MINOCA by optical coherence tomography (OCT) and to correlate with clinical outcomes. METHODS: Patients with MINOCA were divided into 2 groups based on OCT findings: atherosclerotic MINOCA (Ath-MINOCA) and nonatherosclerotic MINOCA (non-Ath-MINOCA). Major adverse cardiac events (MACE) were defined as cardiac death, nonfatal MI, target lesion revascularization, stroke, and rehospitalization for unstable or progressive angina. RESULTS: Among 7,423 patients with a clinical diagnosis of MI who underwent angiography, 190 of 294 MINOCA were studied using OCT. The causes of Ath-MINOCA (n = 99, 52.1%) were plaque erosion (n = 64, 33.7%), plaque rupture (n = 33, 17.4%), and calcified nodule (n = 2, 1.1%) whereas the causes of non-Ath-MINOCA (n = 91, 47.9%) were spontaneous coronary artery dissection (n = 8, 4.2%), coronary spasm (n = 9, 4.7%), and unclassified cause (n = 74, 38.9%). The 1-year MACE was 15.3% for Ath-MINOCA vs 4.5% for non-Ath-MINOCA (P = 0.015). An atherosclerotic cause was an independent predictor of MACE (HR: 5.36 [95% CI: 1.08-26.55]; P = 0.040), mainly driven by target lesion revascularization and rehospitalization, despite the composite endpoint including cardiac death and MI showing no difference. CONCLUSIONS: OCT identified a cause in 61.1% of MINOCA, in which Ath-MINOCA represents an important and distinct MINOCA subset. Ath-MINOCA were more common and associated with worse outcomes. (Incidence Rate of Heart Failure After Acute Myocardial Infarction With Optimal Treatment; NCT03297164; Paradigm Shift in the Treatment of Patients With ACS; NCT02041650).
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Doença da Artéria Coronariana , Infarto do Miocárdio , Humanos , MINOCA , Tomografia de Coerência Óptica/efeitos adversos , Angiografia Coronária/efeitos adversos , Valor Preditivo dos Testes , Infarto do Miocárdio/etiologia , Prognóstico , Morte , Vasos Coronários/patologia , Fatores de Risco , Doença da Artéria Coronariana/patologiaRESUMO
Nowadays, as a type of orderly and active death determined by genes, programmed cell death (PCD), including apoptosis, pyroptosis, ferroptosis, and necroptosis, has attracted much attention owing to its participation in numerous chronic cardiovascular diseases, especially atherosclerosis (AS), a canonical chronic inflammatory disease featured by lipid metabolism disturbance. Abundant researches have reported that PCD under distinct internal conditions fulfills different roles of atherosclerotic pathological processes, including lipid core expansion, leukocyte adhesion, and infiltration. Noteworthy, emerging evidence recently has also suggested that oxidative stress (OS), an imbalance of antioxidants and oxygen free radicals, has the potential to mediate PCD occurrence via multiple ways, including oxidization and deubiquitination. Interestingly, more recently, several studies have proposed that the mediating mechanisms could effect on the atherosclerotic initiation and progression significantly from variable aspects, so it is of great clinical importance to clarify how OS-mediated PCD and AS interact. Herein, with the aim of summarizing potential and sufficient atherosclerotic therapy targets, we seek to provide extensive analysis of the specific regulatory mechanisms of PCD mediated by OS and their multifaceted effects on the entire pathological atherosclerotic progression.
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This paper utilizes an analytical model of polarization dependent frequency sideband generation via the Kerr effect in a highly nonlinear fiber to determine the state of polarization (SOP) of a laser by all-optical means. Theoretical analysis shows that the power of the nth order sideband generated by the propagation of two lasers with distinct frequencies in the nonlinear medium is proportional to cos 2n(α/2), where α is the angle between the normalized Stokes vectors representing the SOPs of the lasers on the Poincaré sphere. By tailoring the SOP of one laser acting as a reference and experimentally measuring the power of the first order sideband, the SOP of the laser under test is recovered with an error smaller than 10.22° on the Poincaré sphere corresponding to 0.8% the sphere's total area. Comparing the SOPs of two lasers without referencing them to fixed polarizers enables potential applications in remote environmental sensing, novel polarization division multiplexing schemes for enhanced telecommunication data rates, and scientific instrumentation.
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The local temperature and longitudinal strain at spatial resolution of 0.5% of the pulse-width equivalent length along a nonuniform As2Se3-PMMA tapered fiber is investigated by a Brillouin gain-profile tracing method. This scheme uses a 20 ns pump pulse with the pulse-width equivalent length longer than the fiber under test (FUT) of 50 cm nonuniform As2Se3-PMMA tapered fiber. The whole interaction process of long pump pulse is investigated including pump pulse entering the FUT, overlapping completely with FUT and leaving the FUT. The evolution of Brillouin gain spectrum (BGS) along the nonuniform fiber is formed by the subtraction of frequency-domain BGS of two adjacent sensing points in the trailing edge (where the pump pulse leaves the FUT) of the BOTDA spectrum. The trailing part is preferred due to the pre-amplified acoustic field by the long pumping pulse. Then the local responses of temperature and wide-range longitudinal strain with high spatial resolution of 1.1 cm along the nonuniform As2Se3-PMMA tapered fibers are investigated. The change of the local temperature and strain shifts the BGS that is different along the nonuniform fibers, which forms the distributed measurement. The spatial resolution, the fiber length of the detected section in the proposed method, is 1.1 cm for the local temperature and longitudinal strain measurement, which is 0.5% of the pulse-width equivalent length and is limited by the sampling rate of data acquisition and the fall-time of the pump pulse.
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Natural antioxidants represented by quercetin have been documented to be effective against atherosclerosis. However, the related mechanisms remain largely unclear. In this study, we identified a novel anti-atherosclerotic mechanism of quercetin inhibiting macrophage pyroptosis by activating NRF2 through binding to the Arg483 site of KEAP1 competitively. In ApoE-/- mice fed with high fat diet, quercetin administration attenuated atherosclerosis progression by reducing oxidative stress level and suppressing macrophage pyroptosis. At the cellular level, quercetin suppressed THP-1 macrophage pyroptosis induced by ox-LDL, demonstrated by inhibiting NLRP3 inflammasome activation and reducing ROS level, while these effects were reversed by the specific NRF2 inhibitor (ML385). Mechanistically, quercetin promoted NRF2 to dissociate from KEAP1, enhanced NRF2 nuclear translocation as well as transcription of downstream antioxidant protein. Molecular docking results suggested that quercetin could bind with KEAP1 at Arg415 and Arg483. In order to verify the binding sites, KEAP1 mutated at Arg415 and Arg483 to Ser (R415S and R483S) was transfected into THP-1 macrophages, and the anti-pyroptotic effect of quercetin was abrogated by Arg483 mutation, but not Arg415 mutation. Furthermore, after administration of adeno associated viral vector (AAV) with AAV-KEAP1-R483S, the anti-atherosclerotic effects of quercetin were almost abolished in ApoE-/- mice. These findings proved quercetins suppressed macrophage pyroptosis by targeting KEAP1/NRF2 interaction, and provided reliable data on the underlying mechanism of natural antioxidants to protect against atherosclerosis.
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Brillouin dynamic gratings (BDG) can measure the distributed birefringence of polarization-maintaining fibers (PMF), however, its sensing range is limited by both stimulated Brillouin scattering depletion and fiber losses in PMF, which are significantly higher than those in standard single-mode fibers. In this work, we theoretically and experimentally verify that BDG can be sustained over ultra-long distances when assisted by distributed Brillouin amplification, significantly extending the distributed birefringence measurement distance. Using an optical frequency comb pumped by a narrow linewidth laser to both generate and interrogate the amplified BDG, a birefringence measurement accuracy of 7.5 × 10-9 was achieved over 7 km sensing length, more than double the longest range reported. This opens a new opportunity to investigate small birefringence changes due to nonlinear optics effects and monitoring fiber network security from eavesdropping.