Current Confinement Effect on the Performance of Blue Light Micro-LEDs with 10 µm Dimension.

The current confinement effect on the micro-LED (µLED) with a 10 µm dimension was simulated using SpeCLED software. In this study, three p-contact sizes were considered: 2 µm × 2 µm, 5 µm × 5 µm, and 8 µm × 8 µm dimensions for µLEDs with a 10 µm dimension. According to the simulation data, the highest external quantum efficiency (EQE) of 13.24% was obtained with a 5 µm × 5 µm contact size. The simulation data also showed that the µLEDs with narrow contact sizes experienced higher operating temperatures due to the current crowding effect. The experimental data revealed a red-shift effect in narrow contact sizes, indicating higher heat generation in those devices. As the contact sizes increased from 2 to 8 µm, the turn-on voltage decreased due to lower equivalent resistance. Additionally, the leakage current increased from 44 pA to 1.6 nA at a reverse voltage of -5 V. The study found that the best performance was achieved with a contact ratio of 0.5, which resulted in the highest EQE at 9.95%. This superior performance can be attributed to the better current confinement of the µLED compared to the µLED with a contact ratio of 0.8, resulting in lower leakage current and improved current spreading when compared to the µLED with a contact ratio of 0.2.

Improved electrical properties of micro light-emitting diode displays by ion implantation technology.

Generally, the inductively coupled plasma-reactive ion etching (ICP-RIE) mesa technology was used to remove p-GaN/MQWs and expose n-GaN for electrical contact in a fabricated micro light-emitting diode (µLED). In this process, the exposed sidewalls were significantly damaged which result in small-sized µLED presenting a strong size-dependent influence. Lower emission intensity was observed in the µLED chip, which can be attributed to the effect of sidewall defect during etch processing. To reduce the non-radiative recombination, the ion implantation using an As+ source to substitute the ICP-RIE mesa process was introduced in this study. The ion implantation technology was used to isolate each chip to achieve the mesa process in the µLED fabrication. Finally, the As+ implant energy was optimized at 40 keV, which exhibited excellent current-voltage characteristics, including low forward voltage (3.2 V @1 mA) and low leakage current (10-9 A@- 5 V) of InGaN blue µLEDs. The gradual multi-energy implantation process from 10 to 40 keV can further improve the electrical properties (3.1 V @1 mA) of µLEDs, and the leakage current was also maintained at 10-9 A@- 5 V.

Comparisons Between Different Anti-osteoporosis Medications on Postfracture Mortality: A Population-Based Study.

CONTEXT: Osteoporosis is becoming a global epidemic in aging societies. Anti-osteoporotic medications can prevent fractures, and their pleiotropic effect on mortality is interesting but not well compared among each other. OBJECTIVE: To provide real-world evidence on the pleiotropic effect of different anti-osteoporotic medications on all-cause mortality, stratified by fracture site, sex, and age. METHODS: This longitudinal population-based postfracture cohort study, included mega-data from subjects ≥40 years of age with osteoporotic fracture who used anti-osteoporotic medications as recorded in Taiwan's National Health Insurance Research Database from 2009 to 2017 and followed until 2018. A multivariate Cox proportional hazards model with immortal time bias was used to assess the relationship between fracture sites and mortality stratified by anti-osteoporosis medication. RESULTS: A total of 46 729 subjects with an average age of 74.45 years (80.0% female) and a mean follow-up period of 4.73 years were enrolled. In the total fracture group, compared with raloxifene and bazedoxifene, we found that alendronate/risedronate (hazard ratio [HR] 0.83; 95% CI, 0.79-0.88), denosumab (HR 0.86; 95% CI, 0.81-0.91), and zoledronic acid (HR 0.78; 95% CI, 0.73-0.84) resulted in significantly lower mortality. Similar trends were observed in the hip, vertebral, or nonhip/nonvertebral fracture groups. Subjects receiving long-acting zoledronic acid showed the lowest mortality in the subanalysis according to sex or age over 65 years. CONCLUSION: This real-world mega-data study suggests that the usage of osteoporotic medication, especially a long-acting regimen, may lower postfracture mortality.

Somatic A-to-I RNA-edited RHOA isoform 2 specific-R176G mutation promotes tumor progression in lung adenocarcinoma.

Adenosine-to-inosine (A-to-I) RNA editing is the most common posttranscriptional editing to create somatic mutations and increase proteomic diversity. However, the functions of the edited mutations are largely underexplored. To identify novel targets in lung adenocarcinoma (LUAD), we conducted a genome-wide somatic A-to-I RNA editing analysis of 23 paired adjacent normal and LUAD transcriptomes and identified 26,280 events, including known nonsynonymous AZIN1-S367G and novel RHOAiso2 (RHOA isoform 2)-R176G, tubulin gamma complex associated protein 2 (TUBGCP2)-N211S, and RBMXL1-I40 M mutations. We validated the edited mutations in silico in multiple databases and in newly collected LUAD tissue pairs with the SEQUENOM MassARRAY® and TaqMan PCR Systems. We selected RHOAiso2-R176G due to its significant level, isoform-specificity, and being the most common somatic edited nonsynonymous mutation of RHOAiso2 to investigate its roles in LUAD tumorigenesis. RHOAiso2 is a ubiquitous but low-expression alternative spliced isoform received a unique Alu-rich exon at the 3' RHOA mRNA to become an editing RNA target, leading to somatic hypermutation and protein diversity. Interestingly, LUAD patients harboring the RHOAiso2-R176G mutation were associated with aberrant RHOA functions, cancer cell proliferation and migration, and poor clinical outcomes in transcriptome analysis. Mechanistically, RHOAiso2-R176G mutation-expressing LUAD cells potentiate RHOA-guanosine triphosphate (GTP) activity to phosphorylate ROCK1/2 effectors and enhance cell proliferation and migration in vitro and increase tumor growth in xenograft and systemic metastasis models in vivo. Taken together, the RHOAiso2-R176G mutation is a common somatic A-to-I edited mutation of the hypermutated RHOA isoform 2. It is an oncogenic and isoform-specific theranostic target that activates RHOA-GTP/p-ROCK1/2 signaling to promote tumor progression.

Effects of ITO Contact Sizes on Performance of Blue Light MicroLEDs.

In this study, the effect of ITO contact ratio for blue light micro-light-emitting diode (µLED) with dimensions 40 µm × 40 µm was assessed. The contact ratio from 0.2 to 0.8 was designed for the ratio of electrode area to light-emitting area. As the contact ratio increased from 0.2 to 0.8, the turn-on voltage of µLED decreased. It could be due to the short lateral diffusion length in multiple quantum wells (MQW) and lower parallel resistance for the µLED with a large contact ratio. The leakage currents of single µLED were below 5.1 × 10-9 A, no matter the contact ratio. It means that the contact ratio does not affect the leakage current as measured on single chip. Moreover, µLED array with a 0.8 contact ratio presented the highest output power than other samples (5.25 mW as the current density of 1875 A/cm2). It could attribute to the MQWs usage, the metal contact reflective behavior and less current crowding, which generated more carriers and extracted more lighting from the µLED. The simulation data using SpeCLED software agreed well with these experiments, and µLED with a 0.8 contact ratio showed the best optoelectronic properties.

Study on the performance of high-voltage deep ultraviolet light-emitting diodes.

This study fabricated high-voltage, low-current DUV-LEDs by connecting two devices. Due to better current spreading and the enhanced reflective mirror effect, high-voltage devices present a higher dynamic resistance, emission output power, wall-plug efficiency, external quantum efficiency, and view angle than single traditional devices. The study found that when the injection current was 320 mA, the maximum output power was exhibited at 47.1 mW in the HV sample. The maximum WPE and EQE of high-voltage DUV-LEDs were 2.46% and 5.48%, respectively. Noteworthily, the redshift wavelength shifted from 287.5 to 280.5 nm, less than the traditional device-from 278 to 282 nm. Further, due to the uniform emission patterns in high-voltage devices, the view angle presents 130 degrees at 100 mA input current. In this study, the high-voltage device showed more excellent properties than the traditional device. In particular, it presented a high potential application in high-voltage circuits, which can remove transformers to eliminate extra power consumption.

Reduced All-Cause Mortality With Bisphosphonates Among Post-Fracture Osteoporosis Patients: A Nationwide Study and Systematic Review.

We assessed the survival outcomes associated with real-world bisphosphonate use, stratified by fracture site, type, administration, and duration of treatment, among patients with osteoporosis. A systematic review that incorporates our findings was conducted to provide up-to-date evidence on survival outcomes with bisphosphonate treatment in real-world settings. Patients diagnosed with osteoporosis who had been hospitalized for major fractures were identified from Taiwan's National Health Insurance Research Database 2008-2017 and followed until 2018. There were 24,390 new bisphosphonate users who were classified and compared with 76,725 nonusers of anti-osteoporosis medications in terms of survival outcomes using Cox model analysis. An inverse probability of treatment weighted Cox model and landmark analyses for minimizing immortal time bias were also performed. Bisphosphonate users vs. nonusers had a significantly lower mortality risk, regardless of fracture site (hazard ratios (95% confidence intervals) for patients with any major fracture, hip fracture, and vertebral fracture: 0.90 (0.88, 0.93), 0.83 (0.80, 0.86), and 0.86 (0.82, 0.89), respectively). Compared with nonuse, zoledronic acid (0.77 (0.73, 0.82)) was associated with the lowest mortality, followed by ibandronate (0.85 (0.78, 0.93)) and alendronate/risedronate (0.93 (0.91, 0.96)). Using bisphosphonates for ≥ 3 years had lower mortality (0.60 (0.53, 0.67)) than using bisphosphonates for < 3 years (0.98 (0.95, 1.01)). Intravenous bisphosphonates had a lower mortality than that of oral bisphosphonates. Our results are consistent with the systematic review findings among real-world populations. In conclusion, bisphosphonate use, especially persistence to intravenous bisphosphonates (e.g., zoledronic acid), may reduce post-fracture mortality among patients with osteoporosis, particularly those with hip/vertebral fractures. This supports the rational use of bisphosphonates in post-fracture care.

A two-photon fluorescence probe for cell membrane imaging under temporal-focusing multiphoton excitation microscopy (TFMPEM).

A small-sized chromophore, BTTA-2OH, manifesting favorable solubility, large two-photon excitation efficiency, and good fluorescence photostability was synthesized to label the membrane of living cells for visualizing the dynamic movement of membrane-related vesicles via a two-photon fluorescence imaging technique based on wavelength-tunable temporal-focusing multiphoton excitation microscopy.

Robust O2 Supplementation from a Trimetallic Nanozyme-Based Self-Sufficient Complementary System Synergistically Enhances the Starvation/Photothermal Therapy against Hypoxic Tumors.

Much effort has been focused on novel nanomedicine for cancer therapy. However, tumor hypoxia limits the efficacy of various cancer therapeutics. Herein, we constructed a self-sufficient hybrid enzyme-based silk fibroin hydrogel system, consisting of Pt-decorated hollow Ag-Au trimetallic nanocages (HGN@Pt) and glucose oxidase (GOx), to supply O2 continuously and consume glucose concurrently and, thereby, synergistically enhance the anti-cancer efficacy of a combined starvation and photothermal therapy operating in a hypoxic tumor microenvironment. Thanks to the cooperative effects of the active surface atoms (resulting from the island-like features of the Pt coating), the intrinsically hollow structure, and the strain effect induced by the trimetallic composition, HGN@Pt displayed efficient catalase-like activity. The enhancement in the generation of O2 through the decomposition of H2O2 mediated by the as-designed nanozyme was greater than 400% when compared with that of hollow Ag-Pt bimetallic nanospheres or tiny Pt nanoparticles. Moreover, in the presence of HGN@Pt, significant amounts of O2 could be generated within a few minutes, even in an acidic buffer solution (pH 5.8-6.5) containing a low concentration of H2O2 (100-500 µM). Because HGN@Pt exhibited a strong surface plasmon resonance peak in the near-infrared wavelength range, it could be used as a photothermal agent for hyperthermia therapy. Furthermore, GOx was released gradually from the SF hydrogel into the tumor microenvironment to mediate the depletion of glucose, leading to glucose starvation-induced cancer cell death. Finally, the O2 supplied by HGN@Pt overcame the hypoxia of the microenvironment and, thereby, promoted the starvation therapeutic effect of the GOx-mediated glucose consumption. Meanwhile, the GOx-produced H2O2 from the oxidation of glucose could be used to regenerate O2 and, thereby, construct a complementary circulatory system. Accordingly, this study presents a self-sufficient hybrid enzyme-based system that synergistically alleviates tumor hypoxia and induces an anti-cancer effect when combined with irradiation of light from a near-infrared laser.

A Comparative Study of Cellular Uptake and Subcellular Localization of Doxorubicin Loaded in Self-Assemblies of Amphiphilic Copolymers with Pendant Dendron by MDA-MB-231 Human Breast Cancer Cells.

Previously synthesized amphiphilic diblock copolymers with pendant dendron moieties have been investigated for their potential use as drug carriers to improve the delivery of an anticancer drug to human breast cancer cells. Diblock copolymer (P71 D3 )-based micelles effectively encapsulate the doxorubicin (DOX) with a high drug-loading capacity (≈95%, 104 DOX molecules per micelle), which is approximately double the amount of drug loaded into the diblock copolymer (P296 D1 ) vesicles. DOX released from the resultant P71 D3 /DOX micelles is approximately 1.3-fold more abundant, at a tumoral acidic pH of 5.5 compared with a pH of 7.4. The P71 D3 /DOX micelles also enhance drug potency in breast cancer MDA-MB-231 cells due to their higher intracellular uptake, by approximately twofold, compared with the vesicular nanocarrier, and free DOX. Micellar nanocarriers are taken up by lysosomes via energy-dependent processes, followed by the release of DOX into the cytoplasm and subsequent translocation into the nucleus, where it exert its cytotoxic effect.

Light-addressable measurements of cellular oxygen consumption rates in microwell arrays based on phase-based phosphorescence lifetime detection.

A digital light modulation system that utilizes a modified commercial digital micromirror device (DMD) projector, which is equipped with a UV light-emitting diode as a light modulation source, has been developed to spatially direct excited light toward a microwell array device to detect the oxygen consumption rate (OCR) of single cells via phase-based phosphorescence lifetime detection. The microwell array device is composed of a combination of two components: an array of glass microwells containing Pt(II) octaethylporphine (PtOEP) as the oxygen-sensitive luminescent layer and a microfluidic module with pneumatically actuated glass lids set above the microwells to controllably seal the microwells of interest. By controlling the illumination pattern on the DMD, the modulated excitation light can be spatially projected to only excite the sealed microwell for cellular OCR measurements. The OCR of baby hamster kidney-21 fibroblast cells cultivated on the PtOEP layer within a sealed microwell has been successfully measured at 104 ± 2.96 amol s(-1) cell(-1). Repeatable and consistent measurements indicate that the oxygen measurements did not adversely affect the physiological state of the measured cells. The OCR of the cells exhibited a good linear relationship with the diameter of the microwells, ranging from 400 to 1000 µm and containing approximately 480 to 1200 cells within a microwell. In addition, the OCR variation of single cells in situ infected by Dengue virus with a different multiplicity of infection was also successfully measured in real-time. This proposed platform provides the potential for a wide range of biological applications in cell-based biosensing, toxicology, and drug discovery.