Tunable spin and valley excitations of correlated insulators in Γ-valley moiré bands.

Moiré superlattices formed from transition metal dichalcogenides support a variety of quantum electronic phases that are highly tunable using applied electromagnetic fields. While the valley degree of freedom affects optoelectronic properties in the constituent transition metal dichalcogenides, it has yet to be fully explored in moiré systems. Here we establish twisted double-bilayer WSe2 as an experimental platform to study electronic correlations within Γ-valley moiré bands. Through local and global electronic compressibility measurements, we identify charge-ordered phases at multiple integer and fractional moiré fillings. By measuring the magnetic field dependence of their energy gaps and the chemical potential upon doping, we reveal spin-polarized ground states with spin-polaron quasiparticle excitations. In addition, an applied displacement field induces a metal-insulator transition driven by tuning between Γ- and K-valley moiré bands. Our results demonstrate control over the spin and valley character of the correlated ground and excited states in this system.

Microneedles loaded with cerium-manganese oxide nanoparticles for targeting macrophages in the treatment of rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a prevalent inflammatory autoimmune disease characterised by persistent inflammation and joint damage with elevated levels of reactive oxygen species (ROS). Current treatment modalities for RA have significant limitations, including poor bioavailability, severe side effects, and inadequate targeting of inflamed joints. Herein, we synthesised cerium/manganese oxide nanoparticles (NPs) as efficient drug carriers with antioxidant and catalytic-like functions that can eliminate ROS to facilitate the polarization of macrophages phenotype from M1 to M2 and alleviate inflammation. Methotrexate (MTX), a first-line RA medication, was loaded into the NPs, which were further modified with bovine serum albumin (BSA) and integrated into dissolving hyaluronic acid-based microneedles (MNs) for transdermal delivery. RESULT: This innovative approach significantly enhanced drug delivery efficiency, reduced RA inflammation, and successfully modulated macrophage polarization toward an anti-inflammatory phenotype. CONCLUSION: This research not only presents a promising drug delivery strategy for RA but also contributes broadly to the field of immune disease treatment by offering an advanced approach for macrophage phenotypic reprogramming.

Strongly suppressed diffuse scattering in periodic graphene metamaterials.

As an emerging two-dimensional material, graphene offers an alternative material platform for exploring new metamaterial phenomena and device functionalities. In this work, we examine diffuse scattering properties in graphene metamaterials. We take periodic graphene nanoribbons as a representative example and show that diffuse reflection in graphene metamaterials as dominated by diffraction orders is restricted to wavelengths less than that of first-order Rayleigh anomaly, and is enhanced by plasmonic resonances in graphene nanoribbons, as similar to metamaterials made of noble metals. However, the overall magnitude of diffuse reflection in graphene metamaterial is less than 10-2 due to the large period to nanoribbon size ratio and ultra-thin thickness of the graphene sheet, which suppress the grating effect from the structural periodicity. Our numerical results indicate that, in contrast to the cases of metallic metamaterials, diffuse scattering plays a negligible role in spectral characterization of graphene metamaterials in cases with large resonance wavelength to graphene feature size ratio, which corresponds to typical chemical vapor deposition (CVD)-grown graphene with relatively small Fermi energy. These results shed light on fundamental properties of graphene nanostructures and are helpful in designing graphene metamaterials for applications in infrared sensing, camouflaging, and photodetection, etc.

Investigation of the influence of blade configuration on the hemodynamic performance and blood damage of the centrifugal blood pump.

PURPOSE: The design and optimization of centrifugal blood pumps are crucial for improved extracorporeal membrane oxygenation system performance. Secondary flow passages are common in centrifugal blood pumps, allowing for a high volume of unstable flow. Traditional design theory offers minimal guidance on the design and optimization of centrifugal blood pumps, so it's critical to understand how design parameter variables affect hydraulic performance and hemocompatibility. METHODS: Computational fluid dynamics (CFD) was employed to investigate the effects of blade number, blade wrap angle, blade thickness, and splitters on pressure head, hemolysis, and platelet activation state. Eulerian and Lagrangian features were used to analyze the flow fields and hemocompatibility metrics such as scalar shear stress, velocity distribution, and their correlation. RESULTS: The equalization of frictional and flow losses allow impellers with more blades and smaller wrap angles to have higher pressure heads, whereas the trade-off between the volume of high scalar shear stress and exposure time allows impellers with fewer blades and larger blade wrap angles to have a lower HI; there are configurations that increase the possibility of platelet activation for both number of blades and wrap angles. The hydraulic performance and hemocompatibility of centrifugal blood pumps are not affected by blade thickness. Compared to the main blades, splitters can improve the blood compatibility of a centrifugal blood pump with a small reduction in pressure head, but there is a trade-off between the length and location of the splitter that suppresses flow losses while reducing the velocity gradient. According to correlation analysis, pressure head, HI, and the volume of high shear stress were all substantially connected, and exposure time had a significant impact on HI. The platelet activation state was influenced by the average scalar shear stress and the volume of low velocity. CONCLUSION: The findings reveal the impact of design variables on the performance of centrifugal blood pumps with secondary flow passages, as well as the relationship between hemocompatibility, hydraulic performance, and flow characteristics, and are useful for the design and optimization of this type of blood pump, as well as the prediction of clinical complications.

Guided-mode resonance with reduced bandwidth in mid-infrared absorption and thermal emission.

Narrowband resonance plays an important role in many optical applications, especially for the development of wavelength-selective properties and enhanced light-matter interaction. In this paper, we demonstrate metal-insulator-metal (MIM) waveguide gratings, which exhibit guided-mode resonance (GMR) with reduced bandwidth in mid-infrared absorption and thermal emission. Our fabricated MIM waveguide grating consists of a copper substrate, a lossless ZnSe film, and a top gold stripe grating. Our measurements reveal strong GMRs with a bandwidth of 1.29% of the central wavelength in both mid-infrared absorption and thermal emission spectra. By varying structural parameters of the MIM waveguide grating, strong absorptions and thermal emissions of GMRs are observed and tuned within the 3-5 µm wavelength range. These results manifest the great potential of engineering infrared properties by using GMR and could be useful for spectral control in a variety of infrared devices.

Gramine promotes functional recovery after spinal cord injury via ameliorating microglia activation.

In recent years, a large number of studies have reported that neuroinflammation aggravates the occurrence of secondary injury after spinal cord injury. Gramine (GM), a natural indole alkaloid, possesses various pharmacological properties; however, the anti-inflammation property remains unclear. In our study, Gramine was investigated in vitro and in vivo to explore the neuroprotection effects. In vitro experiment, our results suggest that Gramine treatment can inhibit release of pro-inflammatory mediators. Moreover, Gramine prevented apoptosis of PC12 cells which was caused by activated HAPI microglia, and the inflammatory secretion ability of microglia was inhibited by Gramine through NF-κB pathway. The in vivo experiment is that 80 mg/kg Gramine was injected orthotopically to rats after spinal cord injury (SCI). Behavioural and histological analyses demonstrated that Gramine treatment may alleviate microglia activation and then boost recovery of motor function after SCI. Overall, our research has demonstrated that Gramine exerts suppressed microglia activation and promotes motor functional recovery after SCI through NF-κB pathway, which may put forward the prospect of clinical treatment of inflammation-related central nervous diseases.

Diffuse reflection in periodic arrayed disk metasurfaces.

Metamaterials of metal-insulator-metal structures represent effective ways in manipulating light absorbance for photodetection, sensing, and energy harvesting etc. Most of the time, specular reflection has been used in characterizing resonances of metamaterials without considering diffuse scattering from their periodic subwavelength units. In this paper, we investigate diffuse reflection in metasurfaces made of periodic metallic disks in the mid-infrared region. Integrating sphere-based spectral measurements indicate that diffuse reflection is dominated by grating diffractions, which cause diffuse scattering in a spectral region with wavelengths less than that of the first order Rayleigh anomaly. The diffuse reflection is greatly enhanced by the metasurface resonance and exhibits a general increase towards shorter wavelengths, which not only causes a significant difference in evaluating the metamaterial resonant absorption efficiency but also a small blue-shift of the resonance frequency. These findings are helpful for designing and analyzing metamaterial resonant properties when diffuse scattering is taken into account.

Effects of chronic nitrate exposure on the intestinal morphology, immune status, barrier function, and microbiota of juvenile turbot (Scophthalmus maximus).

Coming along with high water reuse in sustainable and intensive recirculating aquaculture systems (RASs), the waste products of fish in rearing water is continuously accumulated. Nitrate, the final product of biological nitrification processes, which may cause aquatic toxicity to fish in different degrees when exposed for a long time. Therefore, the present study was conducted to evaluate the impact of chronic nitrate exposure on intestinal morphology, immune status, barrier function, and microbiota of juvenile turbot. For that, groups of juvenile turbot were exposed to 0 (control check, CK), 50 (low nitrate, L), 200 (medium nitrate, M), and 400 (high nitrate, H) mg L-1 nitrate-N in small-sized recirculating aquaculture systems. After the 60-day experiment period, we found that exposure to a high concentration of nitrate-N caused obvious pathological damages to the intestine; for instance, atrophy of intestinal microvilli and necrosis in the lamina propria. Quantitative real-time PCR analysis revealed a significant downregulation of the barrier forming tight junction genes like occludin, claudin-like etc. under H treatment (P < 0.05). Intestinal MUC-2 expression also decreased significantly in the nitrate treatment groups compared to that in the control (P < 0.05). Additionally, the expression of HSP70 and HSP90 heat-shock proteins, toll-like receptor-3 (TLR-3), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) significantly increased (P < 0.05), whereas that of transforming growth factor-ß (TGF-ß), lysozyme (LYS), and insulin-like growth factor-I (IGF-I) significantly decreased with H treatment (P < 0.05). The results also revealed that intestinal microbial community was changed following nitrate exposure and could alter the α-diversity and ß-diversity. Specifically, the proportion of intrinsic flora decreased, whereas that of the potential pathogens significantly increased with M and H treatments (P < 0.05). In conclusion, chronic nitrate exposure could weaken the barrier function and disturb the composition of intestinal microbiota in marine teleosts, thereby harming their health condition.

Investigating the effect of nitrate on juvenile turbot (Scophthalmus maximus) growth performance, health status, and endocrine function in marine recirculation aquaculture systems.

Nitrate (NO3-), a potential toxic nitrogenous compound to aquatic animals, is distributed in aquatic ecosystems worldwide. The aim of this study was to investigate the effects of different NO3- levels on growth performance, health status, and endocrine function of juvenile turbot (Scophthalmus maximus) in recirculating aquaculture systems (RAS). Fish were exposed to 0 mg/L (control, CK), 50 mg/L (low nitrate, LN), 200 mg/L (medium nitrate, MN), and 400 mg/L (high nitrate, HN) NO3-N for 60 d in experimental RAS. Cumulative survival (CS) was significantly decreased with increasing NO3- levels in LN, MN, and HN. The lowest CS was 35% in the HN group. Growth parameters, including absolute growth rate, specific growth rate, and feed conversion rate, were significantly different in HN compared with that in the CK. Histological survey of gills and liver revealed dose-dependent histopathological damage induced by NO3- exposure and significant differences in glutamate pyruvate transaminase and glutamate oxalate transaminase in MN and HN compared with that in the CK. The hepatosomatic index in HN was significantly higher than that in the CK. Additionally, NO3- significantly increased bioaccumulation in plasma in LN, MN, and HN compared to that in the CK. Significant decreases in hemoglobin and increases in methemoglobin levels indicated reduced oxygen-carrying capacity in HN. Additionally, qRT-PCR and enzyme-linked immunosorbent assay (ELISA) were developed to investigate key biomarkers involved in the GH/IGF-1, HPT, and HPI axes. Compared with that in the CK, the abundance of GH, GHRb, and IGF-1 was significantly lower in HN, whereas GHRa did not differ between treatments. The plasma T3 level significantly decreased in LN, MN, and HN and T4 significantly decreased in HN. The CRH, ACTH, and plasma cortisol levels were significantly upregulated in HN compared with that in the CK. We conclude that elevated NO3- exposure leads to growth retardation, impaired health status, and endocrine disorders in turbot and the NO3- level for juvenile turbot culture should not exceed 50 mg/L NO3-N in RAS. Our findings indicate that endocrine dysfunction of the GH/IGF-1, HPT, and HPI axes might be responsible for growth inhibition induced by NO3- exposure.

Tilted Fiber Bragg Grating Sensor Using Chemical Plating of a Palladium Membrane for the Detection of Hydrogen Leakage.

A tilted fiber Bragg grating (TFBG) hydrogen sensor coated with a palladium (Pd) membrane by the electroless plating method is proposed in this paper. A uniform layer of Pd metal is fabricated in aqueous solutions by the chemical coating method, which is used as the sensitive element to detect the change of the surrounding refractive index (SRI) caused by hydrogen absorption. The change in SRI causes an unsynchronized change of the cladding modes and the Bragg peak in the TFBG transmission spectrum, thereby eliminating the cross-sensitivity due to membrane expansion and is able to simultaneously monitor the presence of cracks in the pipe, as well as the hydrogen leakage. By subtracting the wavelength shift caused by fiber expansion, the change of SRI, i.e., the information from the H2 level, can be separately obtained. The drifted wavelength is measured for the H2 concentration below the hydrogen explosion limit between 1% and 4%. The chemical-based coating has the advantages of a low cost, a simple operation, and being suitable for coating on long fiber structures. The proposed sensor is able to detect the H2 signal in 5 min at a 1% H2 concentration. The proposed sensor is proved to be able to monitor the hydrogen level without the cross-sensitivity of temperature variation and expansion strains, so could be a good candidate for security applications in industry.

Laser frequency stabilization using a dispersive line shape induced by Doppler Effect.

We report a simple and robust Doppler-free spectroscopic technique to stabilize a laser frequency to the atomic transition. By employing Doppler Effect on the atomic beam, we obtained a very stable dispersive signal with a high signal-to-noise ratio and no Doppler-background, which served as an error signal to electronically stabilize a laser frequency without modulation. For validating the performance of this technique, we locked a DFB laser to the (133)Cs D2 line and observed an efficient suppression of the frequency noise and a long-term reduction of the frequency drifts in a laboratory environment.

Astaxanthin-mediated Nrf2 activation ameliorates glucocorticoid-induced oxidative stress and mitochondrial dysfunction and impaired bone formation of glucocorticoid-induced osteonecrosis of the femoral head in rats.

BACKGROUND: Osteonecrosis of the femoral head caused by glucocorticoids (GIONFH) is a significant issue resulting from prolonged or excessive clinical glucocorticoid use. Astaxanthin, an orange-red carotenoid present in marine organisms, has been the focus of this study to explore its impact and mechanism on osteoblast apoptosis induced by dexamethasone (Dex) and GIONFH. METHODS: In this experiment, bioinformatic prediction, molecular docking and dynamics simulation, cytotoxicity assay, osteogenic differentiation, qRT-PCR analysis, terminal uridine nickend labeling (TUNEL) assay, determination of intracellular ROS, mitochondrial function assay, immunofluorescence, GIONFH rat model construction, micro-computed tomography (micro-CT) scans were performed. RESULTS: Our research demonstrated that a low dose of astaxanthin was non-toxic to healthy osteoblasts and restored the osteogenic function of Dex-treated osteoblasts by reducing oxidative stress, mitochondrial dysfunction, and apoptosis. Furthermore, astaxanthin rescued the dysfunction in poor bone quality, bone metabolism and angiogenesis of GIONFH rats. The mechanism behind this involves astaxanthin counteracting Dex-induced osteogenic damage by activating the Nrf2 pathway. CONCLUSION: Astaxanthin shields osteoblasts from glucocorticoid-induced oxidative stress and mitochondrial dysfunction via Nrf2 pathway activation, making it a potential therapeutic agent for GIONFH treatment.

Application of machine learning algorithms for accurate determination of bilirubin level on in vitro engineered tissue phantom images.

Neonatal Jaundice is a common occurrence in neonates. High excess bilirubin would lead to hyperbilirubinemia, leading to irreversible adverse damage such as kernicterus. Therefore, it is necessary and important to monitor neonates' bilirubin levels in real-time for immediate intervention. However, current screening protocols have their inherent limitations, necessitating more convenient measurements. In this proof-of-concept study, we evaluated the feasibility of using machine learning for the screening of hyperbilirubinemia in neonates from smartphone-acquired photographs. Different machine learning models were compared and evaluated to gain a better understanding of feature selection and model performance in bilirubin determination. An in vitro study was conducted with a bilirubin-containing tissue phantom to identify potential biological and environmental confounding factors. The findings of this study present a systematic characterization of the confounding effect of various factors through separate parametric tests. These tests uncover potential techniques in image pre-processing, highlighting important biological features (light scattering property and skin thickness) and external features (ISO, lighting conditions and white balance), which together contribute to robust model approaches for accurately determining bilirubin concentrations. By obtaining an accuracy of 0.848 in classification and 0.812 in regression, these findings indicate strong potential in aiding in the design of clinical studies using patient-derived images.

Research Progress in the Field of Tumor Model Construction Using Bioprinting: A Review.

The development of therapeutic drugs and methods has been greatly facilitated by the emergence of tumor models. However, due to their inherent complexity, establishing a model that can fully replicate the tumor tissue situation remains extremely challenging. With the development of tissue engineering, the advancement of bioprinting technology has facilitated the upgrading of tumor models. This article focuses on the latest advancements in bioprinting, specifically highlighting the construction of 3D tumor models, and underscores the integration of these two technologies. Furthermore, it discusses the challenges and future directions of related techniques, while also emphasizing the effective recreation of the tumor microenvironment through the emergence of 3D tumor models that resemble in vitro organs, thereby accelerating the development of new anticancer therapies.

Morroniside-mediated mitigation of stem cell and endothelial cell dysfunction for the therapy of glucocorticoid-induced osteonecrosis of the femoral head.

BACKGROUND: Prolonged use of glucocorticoids (GCs) potentially lead to a condition known as GCs-induced osteonecrosis of the femoral head (GIONFH). The primary mechanisms underlying this phenomenon lies in stem cells and endothelial cells dysfunctions. Morroniside, an iridoid glycoside sourced from Cornus officinalis, possesses numerous biological capabilities, including combating oxidative stress, preventing apoptosis, opposing ischemic effects, and promoting the regeneration of bone tissue. PURPOSE: This study aimed to analyze the impact of Morroniside on Dexamethasone (DEX)-induced dysfunction in stem cells and endothelial cells, and its potential as a therapeutic agent for GIONFH in rat models. METHODS: ROS assay, JC-1 assay, and TUNEL assay were used to detect oxidative stress and apoptosis levels in vitro. For the evaluation of the osteogenic capability of bone marrow-derived mesenchymal stem cells, we employed ALP and ARS staining. Additionally, the angiogenic ability of endothelial cells was assessed using tube formation assay and migration assay. Microcomputed tomography analysis, hematoxylin-eosin staining, and immunohistochemical staining were utilized to evaluate the in vivo therapeutic efficacy of Morroniside. RESULTS: Morroniside mitigates DEX-induced excessive ROS expression and cell apoptosis, effectively reducing oxidative stress and alleviating cell death. In terms of osteogenesis, Morroniside reverses DEX-induced osteogenic impairment, as evidenced by enhanced ALP and ARS staining, as well as increased osteogenic protein expression. In angiogenesis, Morroniside counteracts DEX-induced vascular dysfunction, demonstrated by an increase in tube-like structures in tube formation assays, a rise in the number of migrating cells, and elevated levels of angiogenic proteins. In vivo, our results further indicate that Morroniside alleviates the progression of GIONFH. CONCLUSION: The experimental findings suggest that Morroniside concurrently mitigates stem cell and endothelial cell dysfunction through the PI3K/AKT signaling pathway both in vitro and in vivo. These outcomes suggest that Morroniside serves as a potential therapeutic agent for GIONFH.

Nanoscale multi-beam lithography of photonic crystals with ultrafast laser.

Photonic crystals are utilized in many noteworthy applications like optical communications, light flow control, and quantum optics. Photonic crystal with nanoscale structure is important for the manipulation of light propagation in visible and near-infrared range. Herein, we propose a novel multi beam lithography method to fabricate photonic crystal with nanoscale structure without cracking. Using multi-beam ultrafast laser processing and etching, parallel channels with subwavelength gap are obtained in yttrium aluminum garnet crystal. Combining optical simulation based on Debye diffraction, we experimentally show the gap width of parallel channels can be controlled at nanoscale by changing phase holograms. With the superimposed phase hologram designing, functional structures of complicated channel arrays distribution can be created in crystal. Optical gratings of different periods are fabricated, which can diffract incident light in particular ways. This approach can efficiently manufacture nanostructures with controllable gap, and offer an alternative to the fabrication of complex photonic crystal for integrated photonics applications.

Acute low-dose phosphate disrupts glycerophospholipid metabolism and induces stress in juvenile turbot (Scophthalmus maximus).

Phosphate, as the main nutrient factor of lake eutrophication brought by pollutants discharged from agriculture and industry, is always considered to be a low-toxicity substance to aquatic animals. But the toxicity mechanism is unclear, and published information is limited. In this study, a 96 h acute stress experiment was conducted on juvenile turbot (Scophthalmus maximus) with 0, 10, and 60 mg/L phosphate solutions. Metabonomic analysis revealed that low-dose phosphate (10 mg/L) disrupted glycerophospholipid, purine, and glycolipid metabolism, as well as the tricarboxylic acid (TCA) cycle in juveniles, even at 96 h of stress, which may lead to cell structure damage and signal recognition disorder between cells. Upregulated key genes in the main glycerophospholipid metabolic pathways, which matched the results of the metabolomic study, were detected. Furthermore, low-dose phosphate (10 mg/L) induced oxidative stress and immunotoxicity in fish, resulting in the raising of relevant genes expression such as cat and sod in liver and kidney. In addition, all phosphate-treated groups had induced lesions on gill tissue, as evidenced by pathological observations. In this study on toxic effects on and mechanism of phosphate in aquatic animals using metabolomics, gene expression, and histopathology, we confirm that acute low-dose phosphate could disrupt glycerophospholipid metabolism and induce stress in juvenile turbot. This can provide advice on the amount of phosphate accumulation for marine fish farming and on protecting species diversity and marine ecosystem from the point of view of phosphate toxicity to marine animals.

Visit-to-Visit Blood Pressure Variability and Cardiovascular Outcomes in Patients Receiving Intensive Versus Standard Blood Pressure Control: Insights From the STEP Trial.

BACKGROUND: The clinical prognostic value of visit-to-visit blood pressure (BP) variability (BPV) is debatable, and relative studies among patients receiving BP control to achieve lower BP targets are limited. METHODS: We analyzed a dataset from the STEP trail (Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients) to investigate the relationship between visit-to-visit BPV and cardiovascular events in patients with hypertensive aged 60 to 80 years. Visit-to-visit BPV was defined as the coefficient of variation, SD, delta, average real variability, and variability independent of the mean of BP measured at 6-, 9-, 12-, 15-, and 18-month follow-up visits. We computed hazard ratios for the risks associated with a 1-SD increase in BPV indexes in multivariable cox regression models. RESULTS: Among 7678 patients from the STEP trial, after adjustment for multiple confounders, diastolic BPV indexes were significantly associated with the primary composite end point (hazard ratios ≥1.21; P≤0.029) in the standard group, while there was no association between the clinical outcomes and systolic BPV (P≥0.091). In the intensive treatment group, either systolic or diastolic BPV was no association with clinical outcomes(P≥0.30). Sensitivity analyses using an alternative method to calculate BPV based on 7 BP records generated confirmatory results. CONCLUSIONS: In older adults with hypertension, visit-to-visit diastolic BPV is an independent predictor of adverse health outcomes in the standard treatment group. However, BPV did not have prognostic value in the intensive treatment group. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03015311.

Fluorescence enhancement of organic dyes by femtosecond laser-induced cavitation bubbles for crystal imaging.

Fluorescence from organic dyes can be applied in many research fields such as imaging, bio-sensing and diagnosis. One shortcoming of fluorescence imaging is the limitation in emission intensity. Amplification of fluorescence signals can be achieved by the enhancement of localized electromagnetic fields. Metallic nanoparticles are widely applied to produce plasmon resonance, but they cause thermal damage to fragile bio-materials. In this study, we propose a method for nanoparticle-free fluorescence enhancement by ultrafast laser-induced cavitation bubbles in organic dye solutions. Fluorescence enhancement without the use of nanoparticles prevents potential hazards including thermal effects and biotoxicity. In order to achieve fluorescence enhancement in neat dye solution, cavitation bubbles were induced by focusing an 800 nm ultrafast laser beam. Another 400 nm laser beam was used to pump the gain medium. Fluorescence enhancement was observed in various dye solutions. The intensity and spectra of the fluorescence emission can be controlled by changing the power and focus of the excitation laser. According to time-resolved microscopy and simulation results, the cavity formed by the laser-induced bubbles results in the enhancement of the localized electromagnetic field and induces the amplification of the fluorescence signal. The bubble-enhanced fluorescence emission was used for imaging of protein crystals without causing thermal damage to the samples. This study provides an effective method for bio-compatible fluorescence enhancement and has application prospects in fields such as bio-imaging.

Pharmacological activation of the Nrf2 pathway by Taxifolin remodels articular cartilage microenvironment for the therapy of Osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a widely prevalent degenerative disease marked by extracellular matrix (ECM) degradation, inflammation, and apoptosis. Taxifolin (TAX) is a natural antioxidant possessing various pharmacological benefits, such as combating inflammation, oxidative stress, apoptosis, and serves as a potential chemopreventive agent by regulating genes through an antioxidant response element (ARE)-dependent mechanism. Currently, no studies have investigated the therapeutic impact and precise mechanism of TAX on OA. PURPOSE: The aim of this study is to examine the potential role and mechanism of TAX in reshaping the cartilage microenvironment, thereby offering a stronger theoretical foundation for pharmacologically activating the Nrf2 pathway to manage OA. STUDY DESIGN AND METHODS: The pharmacological effects of TAX were examined in chondrocytes through in vitro studies and in a destabilization of the medial meniscus (DMM) rat model for in vivo analysis. RESULTS: TAX suppresses IL-1ß triggered secretion of inflammatory agents, chondrocyte apoptosis, and ECM degradation, contributing to the remodeling of the cartilage microenvironment. In vivo experiment results demonstrated that TAX counteracted cartilage degeneration induced by DMM in rats. Mechanistic investigations revealed that TAX hinders OA development by reducing NF-κB activation and ROS production through the activation of the Nrf2/HO-1 axis. CONCLUSION: TAX reshapes the articular cartilage microenvironment by suppressing inflammation, mitigating apoptosis, and decreasing ECM degradation through the activation of the Nrf2 pathway. As a result, pharmacological activation of the Nrf2 pathway by TAX holds potential clinical significance in remodeling the joint microenvironment for OA treatment.