Si photonic-electronic monolithically integrated optical receiver with a built-in temperature-controlled wavelength filter.

We present a Si photonic-electronic integrated ring-resonator based optical receiver that contains a temperature-controlled ring-resonator filter (RRF), a Ge photodetector, and receiver circuits in a single chip. The temperature controller automatically determines the RRF temperature at which the maximum transmission of the desired WDM signal is achieved and maintains this condition against any temperature or input wavelength fluctuation. This Si photonic-electronic integrated circuit is realized with 0.25-µm photonic BiCMOS technology, and its operation is successfully confirmed with measurement.

Single-Cell Transcriptome Analysis as a Promising Tool to Study Pluripotent Stem Cell Reprogramming.

Cells are the basic units of all organisms and are involved in all vital activities, such as proliferation, differentiation, senescence, and apoptosis. A human body consists of more than 30 trillion cells generated through repeated division and differentiation from a single-cell fertilized egg in a highly organized programmatic fashion. Since the recent formation of the Human Cell Atlas consortium, establishing the Human Cell Atlas at the single-cell level has been an ongoing activity with the goal of understanding the mechanisms underlying diseases and vital cellular activities at the level of the single cell. In particular, transcriptome analysis of embryonic stem cells at the single-cell level is of great importance, as these cells are responsible for determining cell fate. Here, we review single-cell analysis techniques that have been actively used in recent years, introduce the single-cell analysis studies currently in progress in pluripotent stem cells and reprogramming, and forecast future studies.

Antioxidant and antifatigue effect of a standardized fraction (HemoHIM) from Angelica gigas, Cnidium officinale, and Paeonia lactiflora.

CONTEXT: HemoHIM is an herbal preparation containing Angelica gigas Nakai (Apiaceae), Cnidium officinale Makino (Umbelliferae), and Paeonia lactiflora Pallas (Paeoniaceae) developed for immune regulation. To date, studies on the antifatigue effects of HemoHIM have not been conducted. OBJECTIVE: The antifatigue effects of HemoHIM using models of citrinin and exercise-induced chronic fatigue syndrome were investigated. MATERIALS AND METHODS: Citrinin-induced L6 skeletal muscle cells were treated with HemoHIM (125, 250, and 500 µg/mL). The antioxidant factors were analysed. ICR mice were divided into four groups (n = 10): control, HemoHIM 250, 500 mg/kg, and creatine 300 mg/kg, respectively. Mice were orally administered HemoHIM or creatine for three weeks; during this time, both rotarod test and forced swimming test (FST) were conducted. The latency time was investigated and antioxidant, antifatigue factors were analysed. RESULTS: HemoHIM significantly restored reduced antioxidant enzymes (SOD, CAT, Txn, GPx, GSr, and GCLC in HemoHIM 500 µg/mL) compared to the citrinin group in L6 cells. In vivo, HemoHIM significantly improved the latency time (FST; 279.88 ± 50.32 sec, rotarod test; 552.35 ± 23.50 sec in HemoHIM 500 mg/kg). Moreover, the FST-induced reduction in glucose and glutathione significantly increased by 3-fold (HemoHIM 500 mg/kg) and increase in LDH and MDA were significantly inhibited by 1.6, 2.1-fold in the HemoHIM 500 mg/kg compared to the control group.

Protective effects of a standardized extract (HemoHIM) using indomethacin- and ethanol/HCl-induced gastric mucosal injury models.

Context: HemoHIM is a medicinal herbal preparation of Angelica gigas Nakai (Apiaceae), Cnidium officinale Makino (Umbelliferae), and Paeonia japonica Miyabe (Paeoniaceae) developed for immune regulation. HemoHIM has been investigated for its ability to enhance tissue self-renewal and stimulate immune systems. To date, studies on the protective effects of HemoHIM against gastritis and gastric ulcers have not been conducted. Objective: The protective effects of HemoHIM using models of indomethacin and ethanol/hydrochloric acid (EtOH/HCl)-induced gastric mucosal injury were investigated. Materials and methods: Rats were divided into five groups (n = 10): control, indomethacin, or EtOH/HCl groups, HemoHIM 250, 500 mg kg-1, and cimetidine 100 mg kg-1, respectively. Indomethacin (80 mg kg-1) and 60% EtOH/150 mM HCl were administered orally 1 h after the administration of samples and rats were anesthetized 3 h after induction. The lesion area (%), inhibition ratio (%), and total acidity were investigated, and tissues were histopathologically analyzed using hematoxylin and-eosin (H&E) staining. Results: HemoHIM significantly reduced gastric injury in indomethacin-induced model (250 and 500 mg kg-1; 64.30% and 67.75%, p < 0.001) compared to indomethacin group. In the EtOH/HCl-induced model, HemoHIM reduced gastric lesion (250 and 500 mg kg-1; 61.05% and 73.37%, p < 0.001) and gastric acidity (250 and 500 mg kg-1; 37.80 and 45.20 meq L-1, p < 0.001) compared to EtOH/HCl group. H&E staining of the gastric mucosa showed decreased erosion and hemorrhage in HemoHIM group compared to EtOH/HCl group. Discussion and conclusions: Based on the results, HemoHIM is potential candidate for the treatment of gastritis and gastric ulcers.

Impact of a Delayed Laparoscopic Appendectomy on the Risk of Complications in Acute Appendicitis: A Retrospective Study of 4,065 Patients.

BACKGROUND: Urgent surgery performed for appendicitis is hypothesized to avoid complications such as perforation or abscess. This study aimed to evaluate the effect of the timing of surgery on the complications of laparoscopic appendectomy. METHODS: A retrospective review of 4,065 patients who underwent a laparoscopic appendectomy was conducted. The demographic data, time of presentation, physical findings, diagnostic data and complications were recorded. The patients were divided into 4 groups (Group A, 0-6 h; Group B, 6-12 h; Group C, 12-18 h; Group D, over 18 h) based on the time elapsed from the evaluation at the emergency room to the appendectomy. RESULTS: Group A consisted of 2,084 (51.3%) patients, Group B consisted of 1,553 (38.2%) patients, Group C consisted of 388 (9.5%) patients and Group D consisted of 40 (1.8%) patients. A perforated appendicitis was observed in 560 (13.8%) patients. Postoperative complications developed in 293 (7.2%) patients. No significant differences in perforation and postoperative complications were observed between the 4 groups. CONCLUSION: The timing of surgery did not affect the incidence of complications or perforated appendicitis.

Effectiveness and Factors Associated with Epidural Decompression and Adhesiolysis Using a Balloon-Inflatable Catheter in Chronic Lumbar Spinal Stenosis: 1-Year Follow-Up.

OBJECTIVES: This study aimed to investigate the efficacy of the combined balloon decompression with a balloon-inflatable catheter (ZiNeu) in addition to conventional epidural adhesiolysis, and to identify factors that predict patient responses. STUDY DESIGN: An institutional single-armed prospective observational study. SUBJECTS: Chronic refractory lumbar spinal stenosis. METHODS: This study was performed in 61 patients with spinal stenosis who suffered from chronic (at least 3 months) lumbar radicular pain with or without lower back pain. Patients had failed to maintain improvement for more than 1 month with conventional epidural injection. The numeric rating scale (NRS) and Oswestry disability index (ODI) were each measured at 1, 3, 6, and 12 months after percutaneous epidural adhesiolysis and balloon decompression with a ZiNeu catheter. RESULTS: The percentage of successful responders was 72.1%, 60.7%, 57.4%, and 36.1% of patients at 1, 3, 6, and 12 months, respectively. A single combined treatment of percutaneous epidural adhesiolysis and balloon decompression with a ZiNeu catheter provided sufficient pain relief and functional improvement in patients with chronic refractory lumbar spinal stenosis, and the improvement was maintained for 12 months (P < 0.001). Multivariate logistic regression analysis showed that absence of diabetes independently predicted successful response at 12 months after percutaneous epidural decompression and adhesiolysis with the balloon catheter (Odds ratio = 0.080; 95% confidence interval = 0.009-0.676; P = 0.020). CONCLUSIONS: The combined epidural adhesiolysis and balloon decompression with a ZiNeu catheter led to significant pain relief and functional improvement in a subset of patients with refractory spinal stenosis.

Efficacy of Retrievable Inferior Vena Cava Filter Placement in the Prevention of Pulmonary Embolism during Catheter-Directed Thrombectomy for Proximal Lower-Extremity Deep Vein Thrombosis.

BACKGROUND: Inferior vena cava (IVC) filter placement is not indicated for thrombolytic interventional treatment for deep vein thrombosis (DVT). We analyzed the efficacy and feasibility of retrievable IVC filter placement for the preventive management of embolic shedding during catheter-directed thrombectomy (CDT) for DVT of lower extremity. METHODS: Seventy patients (35 males and 35 females) who underwent retrievable IVC filter placement to prevent thrombus dislodgement during CDT in all symptomatic DVT with thrombus age suspected within 4 weeks of the lower extremity between March 2008 and January 2014 were included in this study. All patients underwent laboratory blood study, duplex ultrasound and/or computed tomography for diagnosis, treatment, and follow-up in accordance with treatment policy of our Uijeongbu St. Mary's hospital. Two types of retrievable IVC filters (OptEase Filter, Cordis, Roden, The Netherlands; Gunther Tulip Filter, Cook, Bloomington, IN) were used to prevent thromboembolic events during CDT. After filter placement, subcutaneous low-molecular-weight heparin and overlapped to warfarin or new oral anticoagulant tried to achieve a target international normalized ratio (INR) of 2.0-3.0 in warfarin patients. RESULTS: The thrombus was dislodged through the IVC filter during catheter-directed thrombolytic therapy in 22 patients (31.4%). In 22 cases, the thromboses were trapped by the retrievable IVC filter, and follow-up images showed thrombus capture. Thirty-four patients (48.6%) received percutaneous transluminal angioplasty (PTA). Additional stents were inserted in 23 patients (32.8%). Pulmonary embolism (PE) was not observed in patients implanted with retrievable IVC filters. CONCLUSIONS: Our study findings suggest that retrieval IVC filter placement during interventional treatments of DVT of lower extremity such as thrombectomy of vein thrombus with or without stent insertion at compressed deep vein is favorable and effective for protecting against PE or lethal complications. We recommend carefully that before the management of DVT thrombus of lower extremity, retrieval IVC filter placement should be considered for preventing morbidity related with the PE.

KBH-1, an herbal composition, improves hepatic steatosis and leptin resistance in high-fat diet-induced obese rats.

BACKGROUND: KBH-1 is an herbal mixture of Saururus chinensis, Curcuma longa and Polygala tenuifolia. Each herb has been reported to have various pharmaceutical activities; however, the synergistic effect of this herbal composition on obesity has not yet been determined. We investigated the alleviation effect of KBH-1 and its possible molecular mechanism in obesity-induced hepatic steatosis and leptin resistance in the hypothalamus. METHODS: We used HepG2 cells, primary neuronal cells and a high-fat diet (HFD)-induced obesity rat model to determine the effect of KBH-1 in vitro and in vivo on hepatic steatosis and leptin resistance accompanied by obesity. To identify the alleviation effect on lipid accumulation, HepG2 cells stimulated by FFA were stained with Oil Red O; in addition, immunoblotting and qPCR were performed to determine the effect of KBH-1 on the activation of proteins and nuclear enzymes in HepG2 cells and the steatotic liver of HFD-induced obesity rats. To examine the effect of KBH-1 on the leptin resistance of the hypothalamus and its possible molecular mechanism, we examined the effect of KBH-1 on the activation of the leptin resistance-related protein in primary cultured cortical neuron cells and the hypothalamus of an HFD-induced obesity rat model. In addition, we used HPLC analysis to identify the standard compound of KBH-1. RESULTS: KBH-1 not only suppressed the lipid deposition in HepG2 cells exposed to free fatty acids (FFA) but also significantly down-regulated major factors in lipogenesis and up-regulated major factors in lipolysis. Similarly, in a HFD-induced obesity model, KBH-1 improved hepatic steatosis by alleviating the effects on lipogenic genes and kinases. In addition, KBH-1 significantly improved the leptin-mediated signals impaired by obesity or FFA in the obesity model and primary cultured cortical neuron cells. In addition, KBH-1 was analyzed to include six standard compounds using HPLC analysis, among these compounds, onji-saponin B and curcumin were potently suppressed the level of triglycerides. CONCLUSIONS: KBH-1 exhibits alleviating effects by improving hepatic steatosis and leptin resistance by up-regulating the activation of AMPK and suppressing the expression of PPARγ. These findings show the potential of KBH-1 as a functional food supplement or preventive agent in the treatment of obesity.

Clinical symptoms of lumbar spinal stenosis associated with morphological parameters on magnetic resonance images.

PURPOSE: This study aimed to investigate the association between the clinical symptoms of central lumbar spinal stenosis (CLSS) and morphological parameters using magnetic resonance imaging (MRI) data. METHODS: We retrospectively reviewed 117 patients who visited our pain clinic from 2009 to 2013 and were diagnosed as CLSS. All patients underwent MRI of the L-spine and we measured the dural sac cross-sectional area (DSA), spinal canal cross-sectional area (SCA), ligamentum flavum cross-sectional area (LFA) and ligamentum flavum thickness (LFT) at the most stenotic intervertebral level on MRI. Clinical outcomes were investigated using the patient-assessed quantitative measurement of visual analog scale (VAS) and subjective disability was assessed by the Oswestry Disability Index (ODI). Additionally, subjective walking distance (SWD) was also collected from electronic medical records. RESULTS: There were no statistically significant correlations found between the VAS score and the DSA, SCA, LFA, and LFT. A statistically significant linear association existed between the DSA and SCA and the subjective walking distance (r=0.201, P=0.045 and r=0.198, P=0.049, respectively) indicating that the larger the DSA or SCA, the longer the SWD before the occurrence of claudication. The LFA and LFT were significantly correlated with the ODI score (r=0.249, P=0.007 and r=0.250, P=0.007, respectively). CONCLUSION: Larger LFA and LFT values are associated with higher ODI values. A larger DSA and SCA are associated with a longer SWD before claudication occurs. To evaluate CLSS patients, clinicians should more carefully inspect the integral morphological parameters than the individual morphological parameters.

Vigna angularis inhibits IL-6-induced cellular signalling and ameliorates collagen-induced arthritis.

OBJECTIVES: The present study was conducted in order to assess whether extracts or isolated compounds from Vigna angularis were able to suppress IL-6 signalling and to show the therapeutic effect on collagen-induced arthritis (CIA) in mice. METHODS: The effect of V. angularis on IL-6 signalling was studied by measuring Stat3-dependent luciferase activity, expression of inflammation-related genes, and phosphorylation of Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated kinase (ERK) induced by IL-6. CIA was induced by immunizing with bovine type II collagen. V. angularis extract (VAE) was administrated orally at 50 and 100 mg/kg from day 1 to day 28. Induction of arthritis was evaluated with a visual scoring system and histological analysis. RESULTS: Extracts or two triterpenoid compounds from V. angularis showed potent inhibitory effects on pSTAT3-inducible luciferase activity, STAT3 tyrosine phosphorylation and the expression of inflammation-related genes induced by IL-6. Administration of VAE significantly suppressed the progression of CIA, accompanied by a reduced antibody response to type II collagen and protection from tissue damage in knee joints. CONCLUSION: Administration of VAE has a therapeutic effect on CIA and this effect is associated with the inhibitory activity on IL-6/STAT3 signalling. These results suggest that extracts or compounds from V. angularis could be a useful treatment for diseases related to IL-6, including RA.

Energy Metabolism in Human Pluripotent Stem and Differentiated Cells Compared Using a Seahorse XF96 Extracellular Flux Analyzer.

Evaluating cell metabolism is crucial during pluripotent stem cell (PSC) differentiation and somatic cell reprogramming as it affects cell fate. As cultured stem cells are heterogeneous, a comparative analysis of relative metabolism using existing metabolic analysis methods is difficult, resulting in inaccuracies. In this study, we measured human PSC basal metabolic levels using a Seahorse analyzer. We used fibroblasts, human induced PSCs, and human embryonic stem cells to monitor changes in basal metabolic levels according to cell number and determine the number of cells suitable for analysis. We evaluated normalization methods using glucose and selected the most suitable for the metabolic analysis of heterogeneous PSCs during the reprogramming stage. The response of fibroblasts to glucose increased with starvation time, with oxygen consumption rate and extracellular acidification rate responding most effectively to glucose 4 hours after starvation and declining after 5 hours of starvation. Fibroblasts and PSCs achieved appropriate responses to glucose without damaging their metabolism 2∼4 and 2∼3 hours after starvation, respectively. We developed a novel method for comparing basal metabolic rates of fibroblasts and PSCs, focusing on quantitative analysis of glycolysis and oxidative phosphorylation using glucose without enzyme inhibitors. This protocol enables efficient comparison of energy metabolism among cell types, including undifferentiated PSCs, differentiated cells, and cells undergoing cellular reprogramming, and addresses critical issues, such as differences in basal metabolic levels and sensitivity to normalization, providing valuable insights into cellular energetics.

Air-ring microstructure arrays for enhanced light extraction from a face-up light-emitting diode.

In this Letter, a light-emitting diode (LED) with prism-shaped-air-ring microstructures (PSAMs) formed on flat sapphire substrate is demonstrated as an alternative design to face-up LEDs on patterned sapphire substrate (PSS) for enhanced light extraction efficiency. In this LED design, the emitted photons can be deflected to the top of the chip for its effective extraction, contrary to the PSS-LED wherein photons are guided to sapphire and get absorbed by packaging materials. The PSAM-LED showed an enhancement in the radiometric power as high as 10% with a low far-field angle of 129° over that of a PSS-LED under an injection current of 20 mA.

Albumin-binding photosensitizer capable of targeting glioma via the SPARC pathway.

BACKGROUND: Malignant glioma is among the most lethal and frequently occurring brain tumors, and the average survival period is 15 months. Existing chemotherapy has low tolerance and low blood-brain barrier (BBB) permeability; therefore, the required drug dose cannot be accurately delivered to the tumor site, resulting in an insufficient drug effect. METHODS: Herein, we demonstrate a precision photodynamic tumor therapy using a photosensitizer (ZnPcS) capable of binding to albumin in situ, which can increase the permeability of the BBB and accurately target glioma. Albumin-binding ZnPcS was designed to pass through the BBB and bind to secreted protein acidic and rich in cysteine (SPARC), which is abundant in the glioma plasma membrane. RESULTS: When the upper part of a mouse brain was irradiated using a laser (0.2 W cm- 2) after transplantation of glioma and injection of ZnPcS, tumor growth was inhibited by approximately 83.6%, and the 50% survival rate of the treatment group increased by 14 days compared to the control group. In glioma with knockout SPARC, the amount of ZnPcS entering the glioma was reduced by 63.1%, indicating that it can target glioma through the SPARC pathway. CONCLUSION: This study showed that the use of albumin-binding photosensitizers is promising for the treatment of malignant gliomas.

Cyclic Stretch Promotes Cellular Reprogramming Process through Cytoskeletal-Nuclear Mechano-Coupling and Epigenetic Modification.

Advancing the technologies for cellular reprogramming with high efficiency has significant impact on regenerative therapy, disease modeling, and drug discovery. Biophysical cues can tune the cell fate, yet the precise role of external physical forces during reprogramming remains elusive. Here the authors show that temporal cyclic-stretching of fibroblasts significantly enhances the efficiency of induced pluripotent stem cell (iPSC) production. Generated iPSCs are proven to express pluripotency markers and exhibit in vivo functionality. Bulk RNA-sequencing reveales that cyclic-stretching enhances biological characteristics required for pluripotency acquisition, including increased cell division and mesenchymal-epithelial transition. Of note, cyclic-stretching activates key mechanosensitive molecules (integrins, perinuclear actins, nesprin-2, and YAP), across the cytoskeletal-to-nuclear space. Furthermore, stretch-mediated cytoskeletal-nuclear mechano-coupling leads to altered epigenetic modifications, mainly downregulation in H3K9 methylation, and its global gene occupancy change, as revealed by genome-wide ChIP-sequencing and pharmacological inhibition tests. Single cell RNA-sequencing further identifies subcluster of mechano-responsive iPSCs and key epigenetic modifier in stretched cells. Collectively, cyclic-stretching activates iPSC reprogramming through mechanotransduction process and epigenetic changes accompanied by altered occupancy of mechanosensitive genes. This study highlights the strong link between external physical forces with subsequent mechanotransduction process and the epigenetic changes with expression of related genes in cellular reprogramming, holding substantial implications in the field of cell biology, tissue engineering, and regenerative medicine.

High performance of InGaN light-emitting diodes by air-gap/GaN distributed Bragg reflectors.

The effect of air-gap/GaN DBR structure, fabricated by selective lateral wet-etching, on InGaN light-emitting diodes (LEDs) is investigated. The air-gap/GaN DBR structures in LED acts as a light reflector, and thereby improve the light output power due to the redirection of light into escape cones on both front and back sides of the LED. At an injection current of 20 mA, the enhancement in the radiometric power as high as 1.91 times as compared to a conventional LED having no DBR structure and a far-field angle as low as 128.2° are realized with air-gap/GaN DBR structures.

Improving the optical performance of InGaN light-emitting diodes by altering light reflection and refraction with triangular air prism arrays.

The effect of triangular air prism (TAP) arrays with different distance-to-width (d/w) ratios on the enhancement of light extraction efficiency (LEE) of InGaN light-emitting diodes (LEDs) is investigated. The TAP arrays embedded at the sapphire/GaN interface act as light reflectors and refractors, and thereby improve the light output power due to the redirection of light into escape cones on both the front and back sides of the LED. Enhancement in radiometric power as high as 117% and far-field angle as low as 129° are realized with a compact arrangement of TAP arrays compared with that of a conventional LED made without TAP arrays under an injection current of 20 mA.

Treatment of striae distensae using needling therapy: a pilot study.

BACKGROUND: Striae distensae are dermal scars characterized by flattening and atrophy of the epidermis. Although many treatment modalities have been attempted with variable results, there is no criterion standard treatment modality for striae distensae. OBJECTIVES: To evaluate the effectiveness and safety of a disk microneedle therapy system (DTS) in the treatment of striae distensae. MATERIALS AND METHODS: Sixteen Korean volunteers with striae distensae alba or rubra were enrolled. Patients received three treatments using a DTS at 4-week intervals. Clinical response to treatment was assessed by comparing pre- and post-treatment clinical photographs, skin biopsies, and patient satisfaction scores. Clinical improvement was assessed using the quartile grading scale. RESULTS: Marked to excellent improvement was noted in seven (43.8%) patients, with minimal to moderate improvement in the remaining nine. Patient satisfaction scores showed that six (37.5%) patients were highly satisfied, eight (50.0%) were somewhat satisfied, and two (12.5%) were unsatisfied. There were no significant side effects except mild pain, erythema, and spotty bleeding. CONCLUSION: Disk microneedle therapy system (DTS) can be effectively and safely used in the treatment of striae distensae.

Comparison of various surface textured layer in InGaN LEDs for high light extraction efficiency.

The various surface texturing effects of InGaN light emitting diodes (LEDs) have been investigated by comparison of experimented data and simulated data. The single-layer and double-layer texturing were performed with the help of ITO nanospheres using wet etching, where the ITO ohmic contact layer and the p-GaN layer are textured using ITO nanospheres as an etch mask. In case of single-layer texturing, p-type GaN layer texturing was more effective than ITO ohmic contact layer texturing. The maximum enhancement of wall-plug efficiency of double-layered textured LEDs is 40% more than conventional LEDs, after packaging at an injected current of 20 mA. The increase of light scattering at the textured GaN surfaces is a major reason for increasing the light extraction efficiency of LEDs.

Effect of embedded silica nanospheres on improving the performance of InGaN/GaN light-emitting diodes.

We report on the effect of embedded silica nanospheres on improving the performance of InGaN/GaN light-emitting diodes (LEDs). The silica nanospehres were coated on the selectively etched GaN using a spin-coating method. With the embedded silica nanospheres structures, we achieved a smaller reverse leakage current due to the selective defect blocking-induced crystal quality improvement. Moreover, the reflectance spectra show strong reflectance modulations due to the different refractive indices between the GaN and silica nanospheres. By using confocal scanning electroluminescence microscopy, a strong light emission from silica nanospheres demonstrates that the silica nanospheres acted as a reflector. We found that the optimized embedded silica nanospheres structure, whose the average size of the etched pits was about 3.5 µm and EPD was 3 x 10(7) cm(-2), could enhance light output power by a factor of 2.23 due to enhanced the probability of light scattering at silica nanospheres.

Enhanced light emission in blue light-emitting diodes by multiple Mie scattering from embedded silica nanosphere stacking layers.

We demonstrate enhanced light emission in blue light-emitting diodes (LEDs) by multiple Mie scattering from embedded silica nanosphere stacking layers (SNSL). A honeycomb cone structure is introduced in the GaN epilayer to confine a maximum number of silica nanospheres (SNs). We found that the light is predominantly directed vertically by scattering and geometrical effect in SNSL embedded LEDs. Consequently, the light output power is enhanced by 2.7 times, which we attribute to the improvement in light extraction efficiency due to the multiple Mie scattering of light from the embedded SNSL. The experimental results are verified by simulation using finite difference time domain method (FDTD).