FGF21 via mitochondrial lipid oxidation promotes physiological vascularization in a mouse model of Phase I ROP.

Hyperglycemia in early postnatal life of preterm infants with incompletely vascularized retinas is associated with increased risk of potentially blinding neovascular retinopathy of prematurity (ROP). Neovascular ROP (Phase II ROP) is a compensatory but ultimately pathological response to the suppression of physiological postnatal retinal vascular development (Phase I ROP). Hyperglycemia in neonatal mice which suppresses physiological retinal vascular growth is associated with decreased expression of systemic and retinal fibroblast growth factor 21 (FGF21). FGF21 administration promoted and FGF21 deficiency suppressed the physiological retinal vessel growth. FGF21 increased serum adiponectin (APN) levels and loss of APN abolished FGF21 promotion of physiological retinal vascular development. Blocking mitochondrial fatty acid oxidation also abolished FGF21 protection against delayed physiological retinal vessel growth. Clinically, preterm infants developing severe neovascular ROP (versus non-severe ROP) had a lower total lipid intake with more parenteral and less enteral during the first 4 weeks of life. Our data suggest that increasing FGF21 levels in the presence of adequate enteral lipids may help prevent Phase I retinopathy (and therefore prevent neovascular disease).

Detection of Ylide Formation between an Alkylidenecarbene and Acetonitrile by Femtosecond Transient Absorption Spectroscopy.

Femtosecond laser flash photolysis of 3-(1a,9b-dihydro-1H-cyclopropa[l]phenanthren-1-ylidene)tetrahydrofuran produces singlet 3-oxacyclopentylidenecarbene which reacts with acetonitrile solvent to form an ylide. This is the first direct detection of ylide formation by an alkylidenecarbene. This new type of ylide was observed to have a broad absorption band in the visible region with λmax ∼450 nm and a lifetime of ∼13.5 ps. As with other "conventional" carbenes (the divalent carbon atom is separately bound to two substituents), this ylide formation method could be also useful for detecting alkylidenecarbenes, especially those that do not absorb at wavelengths suitable for direct observation. Furthermore, the mechanisms by which 3-oxacyclopentylidenecarbene forms the ylide and the overall favorability of ylide formation, vis-à-vis ring expansion of the carbene to strained 3-oxacyclohexyne, were supported by results from density functional theory calculations.

In Situ Magnetic Control of Macroscale Nanoligand Density Regulates the Adhesion and Differentiation of Stem Cells.

Developing materials with remote controllability of macroscale ligand presentation can mimic extracellular matrix (ECM) remodeling to regulate cellular adhesion in vivo. Herein, we designed charged mobile nanoligands with superparamagnetic nanomaterials amine-functionalized and conjugated with polyethylene glycol linker and negatively charged RGD ligand. We coupled negatively a charged nanoligand to a positively charged substrate by optimizing electrostatic interactions to allow reversible planar movement. We demonstrate the imaging of both macroscale and in situ nanoscale nanoligand movement by magnetically attracting charged nanoligand to manipulate macroscale ligand density. We show that in situ magnetic control of attracting charged nanoligand facilitates stem cell adhesion, both in vitro and in vivo, with reversible control. Furthermore, we unravel that in situ magnetic attraction of charged nanoligand stimulates mechanosensing-mediated differentiation of stem cells. This remote controllability of ECM-mimicking reversible ligand variations is promising for regulating diverse reparative cellular processes in vivo.

CKD-602, a topoisomerase I inhibitor, induces apoptosis and cell-cycle arrest and inhibits invasion in cervical cancer.

BACKGROUND: Cervical cancer is the third most common gynecological malignancy. Conventional treatment options are known to be ineffective for the majority of patients with advanced or recurrent cervical cancer. Therefore, novel therapeutic agents for cervical cancer are necessary. In this study, the effects of CKD-602 in cervical cancer were investigated. METHODS: Three established human, immortalized, cervical cancer cell lines (CaSki, HeLa and SiHa) were used in this study. Following treatment with CKD-602, apoptosis was quantified using fluorescein isothiocyanate Annexin V-FITC and propidium iodide (PI) detection kit and cell cycle analysis was analyzed using fluorescence activated cell sorting (FACS). Transwell chambers were used for invasion assays. Western blot assay was performed to analyze proteomics. CaSki cells were subcutaneously injected into BALB/c-nude mice and cervical cancer xenograft model was established to elucidate the antitumor effect of CKD-602 in vivo. RESULTS: Treatment with CKD-602 induced apoptosis and increased expression of the enzyme PARP, cleaved PARP, and BAX. In addition, expression of phosphorylated p53 increased. Cell cycle arrest at G2/M phase and inhibition of invasion were detected after treatment with CKD-602. A significant decrease in cervical cancer tumor volume was observed in this in vivo model, following treatment with CKD-602. CONCLUSIONS: This is the first report of CKD-602 having an antitumor effect in cervical cancer in both an in vitro and in vivo models. The results of this study indicate that CKD-602 may be a novel potential drug, targeting cervical cancer, providing new opportunities in the development of new therapeutic strategies.

Analysis of wide color gamut of green/red bilayered freestanding phosphor film-capped white LEDs for LCD backlight.

In this study, we propose green/red bilayered freestanding phosphor film-capped white light-emitting diodes (W-LEDs) using InGaN blue LEDs and narrowband red and green phosphors to realize a wide color gamut in a liquid crystal display (LCD) backlight system. The narrowband K2SiF6:Mn4+ (KSF) red and SrGa2S4:Eu2+ (SGS) green phosphors are synthesized using a facile etching synthetic process and flux-aided solid state reaction under a H2S atmosphere, respectively, and the freestanding phosphor films are fabricated using a delamination method with water-soluble polymer, polystyrene sulfonic acid, PEDOT/PSS, and interlayered phosphor film. Various phosphor concentrations of green/red bilayered freestanding phosphor film-capped W-LEDs exhibit a correlated color temperature (CCT) and luminous efficacy range of 11,390 K ~6,540 K and 99 lm/W ~124 lm/W, respectively, with an applied current of 60 mA. The W-LED with green (12.5 wt%)/red (40 wt%) bilayered phosphor film, which exhibited luminous efficacy of 105 lm/W at the CCT of 8,330 K, is selected and the color gamut of the bare LED and phosphor RG and the filtered RGB triangle is calculated to be more than ~95% and ~86.4%, respectively, relative to the NTSC in the 1931 CIE color coordinates space.

Enhancement mechanism of quantum yield in core/shell/shell quantum dots of ZnS-AgIn5S8/ZnIn2S4/ZnS.

To achieve a high quantum yield (QY) of nanomaterials suitable for optical applications, we improved the optical properties of AgIn5S8 (AIS) quantum dots (QDs) by employing an alloyed-core/inner-shell/outer-shell (ZAIS/ZIS/ZnS) structure. We also investigated the mechanism of optical transitions to clarify the improvement of QYs. In AIS, the low-energy absorption near the band edge region is attributed to the weakly allowed band gap transition, which gains oscillator strength through state intermixing and electron-phonon coupling. The main photoluminescence is also ascribed to the weakly allowed band gap transition with characteristics of self-trapped excitonic emission. With alloying/shelling processes, the weakly allowed transition is enhanced by the evolution of the electronic structures in the alloyed core, which improves the band gap emission. In shelled structures, the nonradiative process is reduced by the reconstructed lattice and passivated surface, ultimately leading to a high QY of 85% in ZAIS/ZIS/ZnS. These findings provide new insights into the optical transitions of AIS because they challenge previous conclusions. In addition, our work elucidates the mechanism behind the enhancement of QY accomplished through alloying/shelling processes, providing strategies to optimize nontoxic QDs for various applications using a green chemistry approach.

Unlocking synergies: Harnessing the potential of biological methane sequestration through metabolic coupling between Methylomicrobium alcaliphilum 20Z and Chlorella sp. HS2.

A halotolerant consortium between microalgae and methanotrophic bacteria could effectively remediate in situ CH4 and CO2, particularly using saline wastewater sources. Herein, Methylomicrobium alcaliphilum 20Z was demonstrated to form a mutualistic association with Chlorella sp. HS2 at a salinity level above 3.0%. Co-culture significantly enhanced the growth of both microbes, independent of initial inoculum ratios. Additionally, increased methane provision in enclosed serum bottles led to saturated methane removal. Subsequent analyses suggested nearly an order of magnitude increase in the amount of carbon sequestered in biomass in methane-fed co-cultures, conditions that also maintained a suitable cultural pH suitable for methanotrophic growth. Collectively, these results suggest a robust metabolic coupling between the two microbes and the influence of the factors other than gaseous exchange on the assembled consortium. Therefore, multi-faceted investigations are needed to harness the significant methane removal potential of the identified halotolerant consortium under conditions relevant to real-world operation scenarios.

Hidden Direct Bandgap of Bi2O2Se by Se Vacancy and Enhanced Direct Bandgap of Bismuth Oxide Overlayer.

The Bi2O2Se surfaces are well-known to possess 50% Se vacancies, yet they have shown no in-gap states within the indirect bandgap (∼0.8 eV). We have found that the hidden in-gap states arising from the Se vacancies in a 2 × 1 pattern induce a reduced direct bandgap (∼0.5 eV). Such a reduced direct bandgap is responsible for the high electron mobility of Bi2O2Se. Moreover, the Bi oxide overlayers of the Bi thin films, formed through air exposure and annealing, unexpectedly exhibit a large direct bandgap (∼2.1 eV). The simplified fabrication of Bi oxide overlayers provides promise for improving Bi2O2Se electronic devices and enhancing photocatalytic activity.

Engineered Methylococcus capsulatus Bath for efficient methane conversion to isoprene.

Isoprene has numerous industrial applications, including rubber polymer and potential biofuel. Microbial methane-based isoprene production could be a cost-effective and environmentally benign process, owing to a reduced carbon footprint and economical utilization of methane. In this study, Methylococcus capsulatus Bath was engineered to produce isoprene from methane by introducing the exogenous mevalonate (MVA) pathway. Overexpression of MVA pathway enzymes and isoprene synthase from Populus trichocarpa under the control of a phenol-inducible promoter substantially improved isoprene production. M. capsulatus Bath was further engineered using a CRISPR-base editor to disrupt the expression of soluble methane monooxygenase (sMMO), which oxidizes isoprene to cause toxicity. Additionally, optimization of the metabolic flux in the MVA pathway and culture conditions increased isoprene production to 228.1 mg/L, the highest known titer for methanotroph-based isoprene production. The developed methanotroph could facilitate the efficient conversion of methane to isoprene, resulting in the sustainable production of value-added chemicals.

Impact of surface cooling on the water harvesting efficiency of nanostructured window glass.

Humans face a severe shortage of fresh water due to economic growth, climate change, overpopulation, and overutilization. Atmospheric water harvesting (AWH) is a promising solution where clean water is collected from the air through various approaches, including dropwise condensation. However, designing surfaces that balance rapid condensation with efficient water removal is challenging. To address this issue, inspired by the efficient water collection mechanisms in the skin of cold-blooded tree frogs, we propose an eco-friendly approach to collect fresh water from cooled window glass. We fabricated various planar and TiO2 nanostructured surfaces including surfaces mimicking a lotus leaf and a hybrid surface mimicking a desert beetle and a cactus, with different wettability levels such as superhydrophilic, hydrophilic, hydrophobic, superhydrophobic, and biphilic. Sub-cooling of glass substrates between 5 and 15 °C using a Peltier device significantly enhanced the condensation process for all surfaces, with modest dependency on surface properties. This cooling temperature regime could be achieved by geothermal cooling methods that consume little energy. To improve visibility for window applications, we developed hydrophobic polymer nanofilm-modified glass substrates using a simple spin-coating technique, and achieved comparable water harvesting efficiency to that of nanostructured substrates. Our study provides insight into the optimal surface structures and cooling temperature for window glass AWH systems that could be used with an underground cooling system.

Statistical discrimination using different machine learning models reveals dissimilar key compounds of soybean leaves in targeted polyphenol-metric metabolomics in terms of traits and cultivation.

Soybean (SB) leaves (SLs) contain diverse flavonoids with health-promoting properties. To investigate the chemical constituents of SB and their correlations across phenotypes, growing periods, and environmental factors, a validated separation method for mass detection was used with targeted metabolomics. Thirty-six polyphenols (1 coumestrol, 5 flavones, 18 flavonols, and 12 isoflavones) were identified in SLs, 31 of which were quantified. Machine learning (ML) modelling was used to differentiate between the variety, bean color, growing period, and cultivation area and identify the key compounds responsible for these differences. The isoflavone and flavonol profiles were influenced by the growing period and cultivation area based on bootstrap forest modelling. The neural model showed the best predictive capacity for SL differences among the various ML models. Discriminant polyphenols can differ depending on the ML method applied; therefore, a cautious approach should be ensured when using statistical ML outputs, including orthogonal partial least squares discriminant analysis.

In vivo noninvasive mitochondrial redox assessment of the optic nerve head to predict disease.

Eye diseases are diagnosed by visualizing often irreversible structural changes occurring late in disease progression, such as retinal ganglion cell loss in glaucoma. The retina and optic nerve head have high mitochondrial energy need. Early mitochondrial/energetics dysfunction may predict vulnerability to permanent structural changes. In the in vivo murine eye, we used light-based resonance Raman spectroscopy (RRS) to assess noninvasively the redox states of mitochondria and hemoglobin which reflect availability of electron donors (fuel) and acceptors (oxygen). As proof of principle, we demonstrated that the mitochondrial redox state at the optic nerve head correlates with later retinal ganglion loss after acute intraocular pressure (IOP) elevation. This technology can potentially map the metabolic health of eye tissue in vivo complementary to optical coherence tomography, defining structural changes. Early detection (and normalization) of mitochondrial dysfunction before irreversible damage could lead to prevention of permanent neural loss.

Postnatal hyperglycemia alters amino acid profile in retinas (model of Phase I ROP).

Nutritional deprivation occurring in most preterm infants postnatally can induce hyperglycemia, a significant and independent risk factor for suppressing physiological retinal vascularization (Phase I retinopathy of prematurity (ROP)), leading to compensatory but pathological neovascularization. Amino acid supplementation reduces retinal neovascularization in mice. Little is known about amino acid contribution to Phase I ROP. In mice modeling hyperglycemia-associated Phase I ROP, we found significant changes in retinal amino acids (including most decreased L-leucine, L-isoleucine, and L-valine). Parenteral L-isoleucine suppressed physiological retinal vascularization. In premature infants, severe ROP was associated with a higher mean intake of parenteral versus enteral amino acids in the first two weeks of life after adjustment for treatment group, gestational age at birth, birth weight, and sex. The number of days with parenteral amino acids support independently predicted severe ROP. Further understanding and modulating amino acids may help improve nutritional intervention and prevent Phase I ROP.

Isolation of Bovine Milk Exosome Using Electrophoretic Oscillation Assisted Tangential Flow Filtration with Antifouling of Micro-ultrafiltration Membrane Filters.

Tangent flow-driven ultrafiltration (TF-UF) is an efficient isolation process of milk exosomes without morphological deformation. However, the TF-UF approach with micro-ultrafiltration SiNx membrane filters suffers from the clogging and fouling of micro-ultrafiltration membrane filter pores with large bioparticles. Thus, it is limited in the long term, continuous isolation of large quantities of exosomes. In this work, we introduced electrophoretic oscillation (EPO) in the TF-UF approach to remove pore clogging and fouling of with micro-ultrafiltration SiNx membrane filters by large bioparticles. As a result, the combined EPO-assisted TF (EPOTF) filtration can isolate large quantities of bovine milk exosomes without deformation. Furthermore, several morphological and biological analyses confirmed that the EPOTF filtration approach could isolate the milk exosomes in high concentrations with high purity and intact morphology. In addition, the uptake test of fluorescent-labeled exosomes by the keratinocyte cells visualized the biological function of purified exosomes. Hence, compared to the TF-UF process, the EPOTF filtration produced a higher yield of bovine milk exosomes without stopping the filtering process for over 200 h. Therefore, this isolation process enables scalable and continuous production of morphologically intact exosomes from bovine milk, suggesting that high-quality exosome purification is possible for future applications such as drug nanocarriers, diagnosis, and treatments.

High Cell-Density Cultivation of Methylococcus capsulatus Bath for Efficient Methane-Derived Mevalonate Production.

The engineered Methylococcus capsulatus Bath presents a promising approach for converting methane, a potent greenhouse gas, into valuable chemicals. High cell-density culture (HCDC) is necessary for high-titer growth-associated bioproducts, but it often requires time-consuming and labor-intensive optimization processes. In this study, we aimed to achieve efficient HCDC of M. capsulatus Bath by measuring the residual nutrient levels during bioreactor operations and analyzing the specific uptake of each medium component. By controlling the concentrations of nutrients, particularly calcium and phosphorus via intermittent feeding, we achieved a high cell density of 28.2 g DCW/L and a significantly elevated production of mevalonate at a concentration of 1.8 g/L from methane. Our findings demonstrate that the methanotroph HCDC approach presented herein offers a promising strategy for promoting sustainable development, with an exceptional g-scale production titer for value-added synthetic biochemicals.

Comparison of the Right and Left Femur Bone Mineral Densities in Postmenopausal Women.

OBJECTIVES: Bone mineral density (BMD) is measured in the hip and posteroanterior spine; moreover, according to the 2019 International Society for Clinical Densitometry guidelines, unilateral hip can be used. This study aimed to determine whether there is a difference between the BMD of both the femurs in postmenopausal women. METHODS: A total of 343 postmenopausal women were enrolled in this study from January 1, 2010, to December 31, 2019 at a single tertiary hospital. By using the Hologic® Horizon W DXA System, the femur and spine BMD was measured; BMD was recorded in g/cm². Following regions were analyzed in both the femurs: the femur neck, the trochanter area, and total femur. RESULTS: Mean age at imaging was 62 ± 9.7 years, and significant difference in the total BMD of both the femurs (P = 0.003) was observed. In secondary analysis, patients with osteoporosis showed significant contralateral BMD discrepancies in trochanter and total proximal femur BMD (P = 0.041 and P = 0.011, respectively). However, in women with normal BMD, no significant difference between the right and left femur BMD was observed. Furthermore, measurement of solely the unilateral hip can lead to a 16.9% of underdiagnosis in postmenopausal women. CONCLUSIONS: In conclusion, it is necessary to check BMD in both hips, particularly in patients suspected of osteoporosis.

Passivation and Interlayer Effect of Zr(i-PrO)4 on Green CuGaS2/ZnS/Zr(i-PrO)4@Al2O3 and Red CuInS2/ZnS/Zr(i-PrO)4@Al2O3 QD Hybrid Powders.

Broadband emissive I-III-VI quantum dots (QDs) are synthesized as efficient and stable I-III-VI QDs to be used as eco-friendly luminescent materials in various applications. Here, we introduce the additional passivation of zirconium isopropoxide (Zr(i-PrO)4) to improve the optical properties and environmental stability of green-emitting CuGaS2/ZnS (G-CGS/ZnS) and red-emitting CuInS2/ZnS (R-CIS/ZnS) QDs. The photoluminescence quantum yield (PLQY) of both resultant Zr(i-PrO)4-coated G-CGS/ZnS and R-CIS/ZnS QDs reaches similar values of ~ 95%. In addition, the photostability and thermal-stability of G-CGS/ZnS/Zr(i-PrO)4 and R-CIS/ZnS/Zr(i-PrO)4 QDs are improved by reducing the ligand loss via encapsulation of the ligand-coated QD surface with Zr(i-PrO)4. It is also proved that the Zr(i-PrO)4-passivated interlayer mitigates the further degradation of I-III-V QDs from ligand loss even under harsh conditions during additional hydrolysis reaction of aluminum tri-sec-butoxide (Al(sec-BuO)3), forming easy-to-handle G-CGS/ZnS and R-CIS/ZnS QD-embedded Al2O3 powders. Therefore, the introduction of a Zr(i-PrO)4 complex layer potentially provides a strong interlayer to mitigate degradation of I-III-VI QD-embedded Al2O3 hybrid powders as well as passivation layer for protecting I-III-VI QD.

Synthesis of Cs3MnBr5 Green Phosphors Using an Eco-Friendly Evaporative Crystallization Process.

Green (G) and red (R) light-emitting materials, such as quantum dots, perovskite nanocrystals, and inorganic phosphor powders, owing to their excellent optical characteristics, have attracted researchers' attention as color-conversion materials for lighting and display applications. However, these materials contain environmentally harmful elements, such as Pb or Cd, and/or they are synthesized using environmentally harmful synthetic approaches and conditions, involving the use of organic solvents, high pressure, high temperature, harsh atmosphere, and long reaction time. In this study, as an eco-friendly synthetic approach to synthesize lead-free Cs3MnBr5 G powder phosphor, we suggest an evaporative crystallization process of aqueous reactant solution. This synthetic process does not use toxic elements or solvents and the crystallization process utilizes only low reaction temperature and short reaction time under air atmosphere conditions. We successfully synthesized Cs3MnBr5 green powder phosphor, with excellent optical properties, by evaporative heating of a 200 nm syringe-filtered solution at 150 °C for 2 h. The synthesized Cs3MnBr5 phosphors have a photoluminescence quantum yield of 66.3%, a peak wavelength of 520 nm, a narrow bandwidth of 38 nm, and a photoluminescence decay time of 0.34 ms under blue excitation. This phosphor is expected to be a useful alternative G-emitting material that can compete with commercial green quantum dots, perovskite nanocrystals, or inorganic phosphors.

A novel technique for myometrial defect closure after robot-assisted laparoscopic adenomyomectomy: A retrospective cohort study.

OBJECTIVE: To introduce our novel technique for myometrial defect closure after adenomyomectomy. MATERIALS AND METHODS: A retrospective cohort study. A total of 40 patients with adenomyosis who visited our clinic between October 2012 and January 2018 were recruited. Of those 34 patients were eligible for analysis. RESULTS: The mean thickness of the affected uterine wall before surgery was 4.02 cm ± 1.11, dropping to 2.37 cm ± 0.84 postoperatively. This led to a mean drop of 41% in the thickness of the affected wall, which was found to be significant using a paired t-test (p < 0.0001). The mean preoperative pain score was 8.68 ± 1.12, while the postoperative mean was 0.06 ± 0.34. The mean preoperative CA 125 was 121.73 ± 117.29, dropping to 6.95 ± 2.60 postoperatively. This was found to be significantly lower using both the Wilcoxon Signed Rank and Sign tests (p = 0.0156). CONCLUSION: Myometrial defect closure in a layer-by-layer fashion after robot-assisted laparoscopic adenomyomectomy is a reproducible technique. This uterine conserving method was effective in reducing our patients' pain. It may be the solution to maintaining adequate myometrial wall thickness, uterine layer alignment, and endometrial integrity.

Cytochrome P450 oxidase 2J inhibition suppresses choroidal neovascularization in mice.

INTRODUCTION: Choroidal neovascularization (CNV) in age-related macular degeneration (AMD) leads to blindness. It has been widely reported that increased intake of ω-3 long-chain polyunsaturated fatty acids (LCPUFA) diets reduce CNV. Of the three major pathways metabolizing ω-3 (and ω-6 LCPUFA), the cyclooxygenase and lipoxygenase pathways generally produce pro-angiogenic metabolites from ω-6 LCPUFA and anti-angiogenic ones from ω-3 LCPUFA. Howevehr, cytochrome P450 oxidase (CPY) 2C produces pro-angiogenic metabolites from both ω-6 and ω-3 LCPUFA. The effects of CYP2J2 products on ocular neovascularization are still unknown. Understanding how each metabolic pathway affects the protective effect of ω-3 LCPUFA on retinal neovascularization may lead to therapeutic interventions. OBJECTIVES: To investigate the effects of LCPUFA metabolites through CYP2J2 pathway and CYP2J2 regulation on CNV both in vivo and ex vivo. METHODS: The impact of CYP2J2 overexpression and inhibition on neovascularization in the laser-induced CNV mouse model was assessed. The plasma levels of CYP2J2 metabolites were measured by liquid chromatography and tandem mass spectroscopy. The choroidal explant sprouting assay was used to investigate the effects of CYP2J2 inhibition and specific LCPUFA CYP2J2 metabolites on angiogenesis ex vivo. RESULTS: CNV was exacerbated in Tie2-Cre CYP2J2-overexpressing mice and was associated with increased levels of plasma docosahexaenoic acids. Inhibiting CYP2J2 activity with flunarizine decreased CNV in both ω-6 and ω-3 LCPUFA-fed wild-type mice. In Tie2-Cre CYP2J2-overexpressing mice, flunarizine suppressed CNV by 33 % and 36 % in ω-6, ω-3 LCPUFA diets, respectively, and reduced plasma levels of CYP2J2 metabolites. The pro-angiogenic role of CYP2J2 was corroborated in the choroidal explant sprouting assay. Flunarizine attenuated ex vivo choroidal sprouting, and 19,20-EDP, a ω-3 LCPUFA CYP2J2 metabolite, increased sprouting. The combined inhibition of CYP2J2 with flunarizine and CYP2C8 with montelukast further enhanced CNV suppression via tumor necrosis factor-α suppression. CONCLUSIONS: CYP2J2 inhibition augmented the inhibitory effect of ω-3 LCPUFA on CNV. Flunarizine suppressed pathological choroidal angiogenesis, and co-treatment with montelukast inhibiting CYP2C8 further enhanced the effect. CYP2 inhibition might be a viable approach to suppress CNV in AMD.