40 GHz high-efficiency Michelson interferometer modulator on a silicon-rich nitride and thin-film lithium niobate hybrid platform.

We propose and demonstrate a Michelson interferometer modulator with integrated Bragg reflectors on a silicon-rich nitride-thin-film lithium niobate hybrid platform. High-reflectivity Bragg reflectors are placed at the ends of both arms, which double the electro-optic (E-O) interaction length and reduce the velocity mismatch between the microwave and optical wave. The presented Michelson interferometer modulator achieves a measured half-wave voltage length product as low as 1.06 V cm and high-speed modulation up to 70 Gbps. A 3-dB E-O bandwidth beyond 40 GHz is also achieved, which is, to the best of our knowledge, the highest modulation bandwidth of Michelson interferometer modulators.

C-band four-channel CWDM (de-)multiplexers on a thin film lithium niobate-silicon rich nitride hybrid platform.

A four-channel coarse wavelength division multiplexing (CWDM) (de)multiplexer on a thin film lithium niobate-silicon rich nitride hybrid platform has been designed, fabricated, and experimentally measured. Enabled by cascaded multimode waveguide Bragg gratings, the (de)multiplexer has a box-like spectral response, wide 1-dB bandwidth (10 nm), low excess loss (<1.08dB), and low channel cross talk (<-18dB). The central wavelengths of the (de-)multiplexer are 1531/1551/1571/1591 nm, which align to the wavelength grids stipulated by the standard ITU-T G.694.2.

On-chip four-mode (de-)multiplexer on thin film lithium niobate-silicon rich nitride hybrid platform.

A four-mode (de-)multiplexer with transverse electric field light (TE0-TE3) is experimentally demonstrated on a thin film lithium niobate-silicon rich nitride hybrid platform. Enabled by cascaded asymmetrical directional couplers, a (de-)multiplexer with low insertion loss (0.38 dB to 1.6 dB) and low cross talk (-18.46dB to -20.43dB) is obtained at 1550 nm. All channels have cross talk <-16dB from 1480 nm to 1580 nm. The transmission of 4×50 Gbps on-off keying signals is experimentally achieved on the proposed (de-)multiplexer. Experimental results show that the proposed (de-)multiplexer is a promising approach to enhance the transmission capacity in thin film lithium niobate based photonics integrated circuits.

Efficient grating couplers on a thin film lithium niobate-silicon rich nitride hybrid platform.

A grating coupler on a thin film x-cut lithium niobate-silicon rich nitride hybrid platform is proposed and demonstrated. An inverse taper is applied to suppress higher-order mode excitation. A coupling efficiency of -5.82dB and 3 dB bandwidth of 57 nm are obtained near the wavelength of 1550 nm between the standard single-mode fiber (SMF-28) and sub-micrometer waveguides.

TE/TM-pass polarizers based on lateral leakage in a thin film lithium niobate-silicon nitride hybrid platform: publisher's note.

This publisher's note contains a correction to Opt. Lett.45, 4915 (2020)OPLEDP0146-959210.1364/OL.404197.

TE/TM-pass polarizers based on lateral leakage in a thin film lithium niobate-silicon nitride hybrid platform.

TE/TM-pass polarizers based on the lithium niobate-silicon nitride hybrid platform are numerically proposed for the first time, to the best of our knowledge. By utilizing the lateral leakage of a shallowly etched rib waveguide, 1-mm-long TE/TM-pass polarizers with high extinction ratios of 28.72/24.03 dB are obtained. Because of the anisotropy of the lithium niobate, the lateral leakage of TE/TM polarization modes can occur along crystallographic z/y directions, respectively. Such TE/TM-pass polarizers can be integrated in the same wafer.

Portable and Battery-Powered PCR Device for DNA Amplification and Fluorescence Detection.

Polymerase chain reaction (PCR) is a technique for nucleic acid amplification, which has been widely used in molecular biology. Owing to the limitations such as large size, high power consumption, and complicated operation, PCR is only used in hospitals or research institutions. To meet the requirements of portable applications, we developed a fast, battery-powered, portable device for PCR amplification and end-point detection. The device consisted of a PCR thermal control system, PCR reaction chip, and fluorescence detection system. The PCR thermal control system was formed by a thermal control chip and external drive circuits. Thin-film heaters and resistance temperature detectors (RTDs) were fabricated on the thermal control chip and were regulated with external drive circuits. The average heating rate was 32 °C/s and the average cooling rate was 7.5 °C/s. The disposable reaction chips were fabricated using a silicon substrate, silicone rubber, and quartz plate. The fluorescence detection system consisted a complementary metal-oxide-semiconductor (CMOS) camera, an LED, and mirror units. The device was driven by a 24 V Li-ion battery. We amplified HPV16E6 genomic DNA using our device and achieved satisfactory results.

Fluorescence quantification of intracellular materials at the single-cell level by an integrated dual-well array microfluidic device.

We present an integrated microfluidic device for quantifying intracellular materials at the single-cell level. This device combines a dual-well structure and a microfluidic control system. The dual-well structure includes capture wells (20 µm in diameter) for trapping a single cell and reaction wells (200 µm in diameter) for confining reagents. The control system enables a programmable procedure for single-cell analysis. This device achieves highly efficient trapping of single cells, overcoming the Poisson distribution, while affording sufficient biochemical reagents for each isolated reactor. We successfully utilized the presented device to monitor the catalytic interaction between intracellular alkaline phosphatase enzyme and a fluorogenic substrate and to quantify the intracellular glucose concentration of a single K562 cell based on an external standard method. The results demonstrate the feasibility and convenience of our dual-well array microfluidic device as a practical single-cell research tool.

Circulating miRNAs as Potential Biomarkers of Age-Related Macular Degeneration.

Backgroud: Age-related macular degeneration (AMD) is one of the leading causes of irreversible blindness of the elder people. This research was intended to demonstrate the different expression of microRNAs (miRNA) in AMD patients and whether they can be used as biomarkers for AMD. METHODS: MiRNAs expression was measured by microarray of 6 AMD cases and 6 gender matched controls. In a larger-sample case-control study with 126 AMD cases and 140 controls, whole blood samples were detected for the differences of miRNA expression. RESULTS: A total of 216 differentially expressed miRNAs (111 increased and 105 decreased miRNAs) were detected from circulating miRNA microarray. Expanded case-control study results showed that the expression of miR-27a-3p, miR-29b-3p and miR-195-5p was increased significantly. Moreover, the level of miR-27a is higher in patients with wet AMD compared to patients with dry AMD. All 3 miRNAs showed a potential diagnostic value for AMD. CONCLUSION: Circulating miRNA levels were significantly varied in AMD patients. Three miRNAs, miR-27a-3p, miR-29b-3p and the miR-195-5p, might be potential diagnostic biomarkers for AMD.

Effect of bradykinin on TGF-ß1-induced retinal pigment epithelial cell proliferation and extracellular matrix secretion.

BACKGROUND: To evaluate the effect of bradykinin (BK) on TGF-ß1-induced retinal pigment epithelial (RPE) cell proliferation and extracellular matrix secretion and to elucidate the relationship between BK and the Erk/Akt signaling pathway. METHODS: The effects of BK on TGF-ß1-induced RPE cell proliferation were examined via CCK-8 assay. Cell culture supernatant collagen I concentrations were measured via ELISA. Fibronectin (Fn), matrix metalloproteinase-2 (MMP-2) and MMP-9 mRNA and protein expression levels were measured via q-PCR and Western blotting, respectively. Changes in Akt/Erk phosphorylation induced by BK and HOE-140 were evaluated via Western blotting. RESULTS: TGF-ß1 stimulated ARPE-19 cell proliferation, which was inhibited by BK, whose effects were inhibited by HOE-140. BK inhibited TGF-ß1-induced collagen I, Fn and MMP-2 secretion in RPE cells, and these effects were inhibited by HOE-140. BK also inhibited TGF-ß1-induced Akt phosphorylation in RPE cells, and these effects were blocked by HOE-140. BK had no significant effect on Erk-mediated signaling. CONCLUSIONS: The findings from this study indicate that BK could be novel therapeutic targets for the treatment of PVR.

Untargeted Metabolomic Study of Patients with Wet Age-Related Macular Degeneration in Aqueous Humor.

Purpose: The objective of this study was to ascertain metabolic biomarkers and investigate the metabolic alterations associated with aqueous humor (AH) in wet age-related macular degeneration (AMD). Methods: AH samples were collected from a total of 20 participants, including 10 individuals diagnosed with wet AMD and 10 individuals undergoing cataract surgery, serving as the control group. Metabolomics analysis was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify and quantify metabolites. Results: A total of 155 metabolites were identified in the AH samples. Among them, 10 metabolites emerged as potential biomarkers capable of differentiating patients with wet AMD from the control group. In the AH of wet AMD patients, there was increased expression of Cardiolipin (CL) (72:5), Diglyceride (DG) (18:3_18:2), DG (36:5e) and Triglyceride (TG) (24:7), while the expression of Ceramides (Cer) (d32:0), Cer (d34:0), Cer (d36:0), Monogalactosyldiacylglycerol (MGDG) (16:1_18:3), Sphingosine (SPH) (d18:0) and TG (16:0_10:4_16:0) was down regulated. Conclusion: Through metabolomics analysis of AH, this study successfully uncovered valuable metabolic biomarkers linked to wet AMD. These findings contribute to a more comprehensive understanding of the pathogenesis of wet AMD and offer potential avenues for the development of innovative treatment strategies for this condition.

A lipidomic study on the lens epithelial cells of patients with age related cataracts.

Age related cataracts (ARC) represent the main reason for blindness globally. The lens epithelial cells (LECs) participate not only in the metabolism of many substances in the lens but also in maintaining lens transparency. This study used lipidomics to investigate the metabolic differences in LECs of ARC patients with different severity, aiming at identifying potential metabolic biomarkers of ARC. Patients diagnosed with ARC and underwent cataract surgery at Shanghai Tongren Hospital were selected to participate in this study, which were classified as mild ARC group and severe ARC group. During their cataract surgery, anterior lens capsules(LCs) containing LECs were obtained. The lipidomics of LECs were analyzed using the liquid chromatography­mass spectrometry (LC-MS). Potential pathways of lipids were searched for using databases such as the Kyoto Encyclopedia of Genes and Genomes (KEGG) and MetaboAnalyst platform. In LEC lipids, 26 lipids have been identified as potential biomarkers between mild ARC and severe ARC, with AUC values of 0.67-0.94. The pathway analysis results revealed that the Glycerophospholipid (GPL) metabolism was significantly influenced, indicating that these metabolic markers contribute significantly to regulating this pathway. The LEC metabolic spectrum demonstrates a proficient ability to differentiate between patients with varying levels of cataracts. Herein, we have successfully identified potential metabolic biomarkers and pathways that have proven to be valuable in enhancing our understanding of ARC pathogenesis. The finding has translational value for developing new cataract treatment methods in the future.

Prevalence and Risk Factors of Ocular Demodex at Ultra-High Altitude and Sea Level: A Cross-Sectional Study of Shigatse and Shanghai.

Purpose: Demodex infestation is a risk factor for several ocular surface diseases. However, the prevalence of ocular Demodex infection in the ultra-high altitude population is not clear. This study aimed to compare the prevalence and factors associated with Demodex in populations residing in ultra-high altitude region and sea level areas. Methods: Consecutive patients who visited Shigatse People's Hospital (> 4,000 m) and Shanghai Tongren Hospital (sea level) for eye complaints between January 2023 and January 2024 were included. Subjects were divided into ultra-high altitude and sea level groups. All subjects underwent eyelash epilation for ocular Demodex identification and counting. Demographic and lifestyle information was also collected. Results: A total of 517 subjects were eligible, including 255 subjects in the ultra-high-altitude group and 262 subjects in the sea level group. In the overall analysis, the prevalence of ocular Demodex infection was significantly different between the ultra-high-altitude and sea level groups (15.7% vs. 33.2%, P < 0.001). Multiple logistic regression showed that age, time spent outdoors, and makeup were associated with ocular Demodex infection in both groups. In addition, in the ultra-high-altitude group, people who wear sun hats outdoors were more likely to be infected with Demodex. Conclusion: The infection rate of ocular Demodex in the residents of ultra-high altitude area was significantly lower than that in the residents of sea level area, which may be related to lower ambient temperature, lower humidity, and higher solar radiation. Additionally, age, time spent outdoors, and makeup may be associated with ocular Demodex infection.

Patching Retinal Breaks with Chitosan for Retinal Detachment in Rabbits.

BACKGROUND: Rhegmatogenous retinal detachment (RRD) is caused by one or more full-thickness retinal breaks. The current RRD treatments have several drawbacks. Chitosan is one of the most commonly used natural polymers for wound healing and has been demonstrated to be biodegradable, biocompatible, non-toxic, bioadhesive, and bioactive. This study aimed to determine the reliability and effectiveness of chitosan for sealing retinal breaks in rabbits. METHODS: Eighteen blue purple rabbits were randomly divided into three groups: chitosan (n = 6), RRD (n = 6), and control (n = 6). The RRD model was established using vitrectomy, making retinal holes, and subretinal fluid injection in the RRD and chitosan groups. One week after the establishment of the model, chitosan was applied within the range of the holes in the chitosan group, and the vitreous body was filled with perfusion fluid. Except the chitosan treatment, the RRD group underwent the same procedure. Intraocular pressure (IOP) measurement, fundus photography, B-mode ultrasound, optical coherence tomography (OCT), histology, and enzyme linked immunosorbent assay (ELISA) were performed. RESULTS: Retinas of all eyes in the RRD group were detached, whereas those of all eyes in the chitosan group remained attached. The concentrations of epidermal growth factor (EGF), fibroblast growth factor (FGF)-2, transforming growth factor ß (TGF-ß), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and IL-8 in the vitreous fluid of the RRD group were significantly higher than those of the control group (p < 0.05). Furthermore, the concentrations of EGF, FGF-2, TGF-ß, and VEGF in the vitreous fluid of the chitosan group were higher compared to those of the RRD group (p < 0.05), whereas the concentrations of IL-6 and IL-8 were lower (p < 0.05). CONCLUSIONS: Chitosan may be a reliable method for sealing retinal breaks. Moreover, chitosan can maintain high levels of growth factors and reduce inflammatory factors in the vitreous, which may reduce and delay the death of retinal cells and help restore visual function after retinal repositioning.

Relationship Between Risk Factors and Macular Thickness in Patients with Early Diabetic Retinopathy.

Purpose: The purpose of this study was to explore the changes in macular thickness (MT) in normal people, patients without obvious diabetic retinopathy (NDR) and patients with nonproliferative diabetic retinopathy (NPDR) and to study the possible risk factors for early diabetic retinopathy (DR). Methods: Thirty-one healthy individuals, 40 people with no sign of DR and 60 people with mild NPDR were included in this cross-sectional study. All patients underwent a complete ophthalmological examination. Optical coherence tomography (OCT) was used to measure the MT of each participant. The potential relationship between MT and systemic risk factors for DR, including diabetes duration, body mass index (BMI), hemoglobin A1c (HbA1c), serum lipids, and blood pressure, was analyzed. Results: The MT of the right and left eyes in the central and inner ring regions of the NPDR group and NDR group were significantly different from that in the control group. The MTs of the right and left eyes in the central region and inner ring region were also significantly different between the NPDR group and NDR group, but the MTs of the right and left eyes in the outer ring region were not significantly different among the three groups. Diabetic duration, total cholesterol (TC), triglycerides (TGs), systolic pressure, and diastolic pressure were positively correlated with the MT of the right and left eyes in the central region. Conclusion: MT increases, especially in the central region and inner ring, may be the first structural retinal change in diabetic patients and is related to the duration of diabetes, TC, TG, systolic pressure and diastolic pressure.

Evaluation of Foldable Capsular Vitreous Body Implantation Surgery.

Background: Foldable capsular vitreous body (FCVB), a novel artificial vitreous substitute product, has been used clinically in recent years. The aim of this study was to evaluate the outcomes and complications of FCVB implantation surgery during the postoperative period. Methods: We performed a prospective, nonrandomized study from November 2021 to March 2022. Eight patients with severe retinal detachment that could not be easily reattached were included in this study. Before and after surgery, visual acuity (VA), intraocular pressure (IOP), slit-lamp microscopy, optical coherence tomography (OCT), B-scan and CT were performed. Results: After the operation, the FCVB was well distributed in the vitreous cavity and supported the retina according to the B-scan and CT images. During the follow-up period, no vitreous hemorrhage or retinal detachment was found in any of the patients. On the first postoperative day, the average IOP increased from 9.6 ± 7.7 mmHg preoperatively to 13.8 ± 14.3 mmHg. Although the IOP of two patients fell outside the normal range, IOP was finally held steady after the fifth postoperative day in all cases. In addition, three patients (37.5%) experienced eye ache, and after taking a Saridon tablet, the pain was greatly alleviated. Moreover, no adverse events, such as silicone oil (SO) spillage and emulsification or serious complications, were observed. Conclusion: The current vitreous substitute FCVB is effective and safe for treating complicated retinal detachments in ophthalmic applications. Further multiple-center clinical designs should focus on indications and complications of FCVB during long-term follow-up periods.

Metabolomic study of eyeball rupture and patients with cataracts in aqueous humor.

The purpose of the present study was to identify metabolic biomarkers and study the metabolic changes in relation to cataracts and eyeball rupture in human aqueous humor. This case-control study included 3 patients with traumatic ocular rupture treated by surgery as the control group, 10 patients with severe cataracts as the severe cataracts group and 10 patients with mild cataracts as the mild cataracts group. The present study used liquid chromatography-mass spectrometry to analyze the metabolomics of aqueous humor samples. Databases including the Kyoto Encyclopedia of Genes and Genomes and MetaboAnalyst were used to find potential pathways for metabolites. Aqueous humor metabolic spectrum can competently distinguish patients with different degrees of cataracts from the control group. A total of 34 metabolites were identified as potential biomarkers that could distinguish patients with different degrees of cataracts; 36 metabolites were identified as potential biomarkers that could distinguish patients with severe cataracts from the control group; 34 metabolites were identified as potential biomarkers that could distinguish patients with mild cataracts from controls. In pathway analysis, glycerolphospholipid metabolism was highly affected, which meant that these metabolic markers serve an important role in the regulation of this pathway. The present study identified valuable metabolic biomarkers and pathways, which is helpful for an improved understanding of the pathogenesis of cataracts. This discovery has transformation value for the development of new treatment methods for cataracts.

Cytokine and Chemokine Profile Changes in Patients with Neovascular Age-Related Macular Degeneration After Intravitreal Ranibizumab Injection for Choroidal Neovascularization.

OBJECTIVE: To investigate the concentrations of cytokine and chemokines profiling in aqueous humor for choroidal neovascularization (CNV) due to neovascular age-related macular degeneration (nAMD) before and during Intravitreal injection of ranibizumab (IVR) and its relation with the disease's active state. METHODS: The cytokine levels in aqueous humour were detected by the Bio-Plex® 200 System and the Bio-Plex™ Human Cytokine Standard 27-Plex, Group I. Aqueous humour samples of experimental group were collected from 19 patients diagnosed nAMD at baseline and at 1 month after IVR. Aqueous humour samples of control group were collected from 20 patients undergoing cataract surgery. RESULTS: Aqueous humor levels of basic fibroblast growth factor (basic FGF) and RANTES were significantly lower in nAMD patients than in the control group (P=0.044 and P<0.001, respectively). Vascular endothelial growth factor-A (VEGF-A) was significantly higher in nAMD patients than in the control group (P < 0.001). The average Eotaxin levels were significantly higher in nAMD patients after IVR than before (P=0.03). Contrarily, the average VEGF-A levels were significantly lower in AMD patients after IVR than before (P < 0.001). CONCLUSION: Angiogenic, growth factors and inflammatory are involved in the formation of neovascularization of AMD patients. IVR did not cause significant differences in any growth factors or inflammatory cytokines in nAMD patients with the exception of VEGF.

MicroRNA-27a Promotes Oxidative-Induced RPE Cell Death through Targeting FOXO1.

Age-related macular degeneration (AMD) is a multifactor disease, which is primarily characterized by retinal pigment epithelium (RPE) cell loss. Since the retina is the most metabolically active tissue, RPE cells are exposed to consistent oxidative environment. So, oxidation-induced RPE cell death has long been considered a contributor to the onset of AMD. Here, we applied a retinal degeneration (RD) rat model induced by blue light-emitting diode (LED) and a cell model constructed by H2O2 stimulus to mimic the prooxidant environment of the retina. We detected that the expression of miR-27a was upregulated and the expression of FOXO1 was downregulated in both models. So, we furtherly investigated the role of miR-27a-FOXO1 axis in RPE in protesting against oxidants. Lentivirus-mediated RNA was injected intravitreally into rats to modulate the miR-27a-FOXO1 axis. Retinal function and histopathological changes were evaluated by electroretinography (ERG) analysis and hematoxylin and eosin (H&E) staining, respectively. Massive photoreceptor and RPE cell death were examined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The damage to the retina was aggravated in the FOXO1 gene-knockdown and miR-27a-overexpression groups after exposure to LED but was alleviated in the FOXO1 gene-overexpression or miR-27a-knockdown groups. Dual luciferase assay was used to detect the binding site of miR-27a and FOXO1. Upregulated miR-27a inhibited the expression of FOXO1 by directly binding to the FOXO1 mRNA 3'UTR and decreased the autophagy activity of ARPE-19 cells, resulting in the accumulation of reactive oxygen species (ROS) and decrease of cell viability. The results suggest that miR-27a is a negative regulator of FOXO1. Also, our data emphasize the prominent role of miR-27a/FOXO1 axis in modulating ROS accumulation and cell death in RPE cell model under oxidative stress and influencing the retinal function in the LED-induced RD rat model.

Cytokine and chemokine profile changes in patients after intravitreal conbercept injection for center macular edema due to branch retinal vein occlusion.

PURPOSE: This study aimed to ascertain cytokine concentrations in patients with center macular edema (CME) due to branch retinal vein occlusion (BRVO) before and during the period of treatment with intravitreal injection of conbercept (IVC) and to determine the relationship between these concentrations and disease activity. MATERIALS AND METHODS: The Bio-Plex® 200 System and the Bio-PlexTM Human Cytokine Standard 27-Plex, Group I (Bio-Rad, Hercules, California, USA) were used to detect cytokine concentrations in aqueous humour. Experimental aqueous humour samples were collected from 22 patients with CME due to BRVO when IVC was administered at baseline and at 1 month, and control aqueous samples were collected by limbal paracentesis from 16 patients undergoing routine cataract surgery. RESULTS: Significantly higher concentrations of vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), IL-8, interferon gamma-induced protein 10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1) were found in the BRVO group than in the control group. In the BRVO group, VEGF levels were significantly lower one month after IVC than at baseline. However, the other cytokines did not significantly change during IVC treatment. The decreases in VEGF levels were closely related to the decreases in central macular thickness (CMT) and the increases in best-corrected visual acuity (BCVA). CONCLUSIONS: Many factors, such as angiogenic, inflammatory and growth factors, contribute to the pathogenesis of CME due to BRVO. IVC had no significant effect on cytokines other than VEGF in patients with CME due to BRVO. The changes in BCVA and CMT were associated with VEGF levels after IVC treatment.