Exosomal microRNA-92b Is a Diagnostic Biomarker in Breast Cancer and Targets Survival-Related MTSS1L to Promote Tumorigenesis.

Exosomal microRNAs (miRNAs) are novel, non-invasive biomarkers for facilitating communication and diagnosing cancer. However, only a few studies have investigated their function and role in the clinical diagnosis of breast cancer. To address this gap, we established a stable cell line, MDA-MB-231-CD63-RFP, and recruited 112 female participants for serum collection. We screened 88 exosomal miRNAs identified through microarray analysis of 231-CD63 and literature screening using real-time PCR; only exosomal miR-92b-5p was significantly increased in patients with breast cancer. It had a significant correlation with stage and discriminated patients from the control with an AUC of 0.787. Exosomal miR-92b-5p impacted the migration, adhesion, and spreading ability of normal human mammary epithelial recipient cells through the downregulation of the actin dynamics regulator MTSS1L. In clinical breast cancer tissue, the expression of MTSS1L was significantly inversely correlated with tissue miR-92b-5p, and high expression of MTSS1L was associated with better 10-year overall survival rates in patients undergoing hormone therapy. In summary, our studies demonstrated that exosomal miR-92b-5p might function as a non-invasive body fluid biomarker for breast cancer detection and provide a novel therapeutic strategy in the axis of miR-92b-5p to MTSS1L for controlling metastasis and improving patient survival.

O → S Acyl Transfer Directing Human Sera Glycoprotein Immobilization for Breast Cancer Diagnosis.

Breast cancer (BC) is one of the most common malignancies in the world with aberrantly expressed glycans. The different types and stages still limit a comprehensive method in the prediagnosis of BC patients. In this research, a synthetic boronic acid-disulfide (BASS) probe has been developed for the two steps of O → S → N acyl transfer in glycoprotein recognition and labeling. The specificity and sensitivity of this method have been carefully studied in the case of immunoglobulin G, and the labeling efficiency was determined up to 60%. The BASS-functionalized slide is a powerful platform for monitoring the alteration of glycan patterns in human sera. Compared to the samples from healthy individuals, sera of BC patients gave specific patterns to eight lectins binding. The BASS-directed glycoprotein strategy promises a rapid sensing platform for a high-throughput screening of clinical BC samples and could be easily applied to other cancer prediagnoses.

A CT Radiomics-Based Risk Score for Preoperative Estimation of Intraoperative Superior Mesenteric-Portal Vein Involvement in Pancreatic Ductal Adenocarcinoma.

BACKGROUND: The current radiologic criteria for assessing intraoperative superior mesenteric-portal vein (SMPV) involvement (i.e., presence of tumor-SMPV contact >180° or venous deformity) in pancreatic ductal adenocarcinoma (PDAC) are highly specific but insufficiently sensitive. Therefore, development of improved markers for a more accurate prediction is essential. This study aimed to develop a risk score model to estimate SMPV involvement in PDAC using radiomics analysis of computed tomography (CT) images. METHODS: Data from two institution-based cohorts of PDAC patients undergoing preoperative CT scans were used to develop (n = 173) and validate (n = 156) a radiomics-based risk score of SMPV involvement using clinical and imaging variables. A radiomics signature was developed based on 2436 radiomic features extracted from the semi-automatic three-dimensional segmentation ofn CT images. The SMPV involvement risk score was built using multivariate logistic regression and compared with the current radiologic criteria. RESULTS: The study surgically identified SMPV involvement in 59 (34.1%) and 57(36.5 %) patients with PDAC in the development and validation cohorts, respectively. A 12-feature-based radiomics signature achieved areas under receiver operating characteristics curves (AUCs) of 0.89 or greater for estimating SMPV involvement. Multivariate regression identified the radiomics signature and SMPV deformity as associated with SMPV involvement. The risk score model had significantly improved AUC (0.928 vs. 0.768; P < 0.001) and sensitivity (84.2% vs. 66.7%; P = 0.025) in the radiologic evaluation. CONCLUSIONS: The novel risk score in this study, combining radiomics signature and venous deformity, demonstrated promising performance for estimating SMPV involvement preoperatively for patients with PDAC.

Nomogram Estimating Vessels Encapsulating Tumor Clusters in Hepatocellular Carcinoma From Preoperative Gadoxetate Disodium-Enhanced MRI.

BACKGROUND: Vessels encapsulating tumor clusters (VETC) pattern is a novel microvascular pattern associated with poor outcomes of hepatocellular carcinoma (HCC). Preoperative estimation of VETC has potential to improve treatment decisions. PURPOSE: To develop and validate a nomogram based on gadoxetate disodium-enhanced MRI for estimating VETC in HCC and to evaluate whether the estimations are associated with recurrence after hepatic resection. STUDY TYPE: Retrospective. POPULATION: A total of 320 patients with HCC and histopathologic VETC pattern assessment from three centers (development cohort:validation cohort = 173:147). FIELD STRENGTH/SEQUENCE: A3.0  T/turbo spin-echo T2-weighted, spin-echo echo-planar diffusion-weighted, and 3D T1-weighted gradient-echo sequences. ASSESSMENT: A set of previously reported VETC- and/or prognosis-correlated qualitative and quantitative imaging features were assessed. Clinical and imaging variables were compared based on histopathologic VETC status to investigate factors indicating VETC pattern. A regression-based nomogram was then constructed using the significant factors for VETC pattern. The nomogram-estimated VETC stratification was assessed for its association with recurrence. STATISTICAL TESTS: Fisher exact test, t-test or Mann-Whitney test, logistic regression analyses, Harrell's concordance index (C-index), nomogram, Kaplan-Meier curves and log-rank tests. P value < 0.05 was considered statistically significant. RESULTS: Pathological VETC pattern presence was identified in 156 patients (development cohort:validation cohort = 83:73). Tumor size, presence of heterogeneous enhancement with septations or with irregular ring-like structures, and necrosis were significant factors for estimating VETC pattern. The nomogram incorporating these indicators showed good discrimination with a C-index of 0.870 (development cohort) and 0.862 (validation cohort). Significant differences in recurrence rates between the nomogram-estimated high-risk VETC group and low-risk VETC group were found (2-year recurrence rates, 50.7% vs. 30.3% and 49.6% vs. 31.8% in the development and validation cohorts, respectively). DATA CONCLUSION: The nomogram integrating gadoxetate disodium-enhanced MRI features was associated with VETC pattern preoperatively and with postoperative recurrence in patients with HCC. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Adding liver R2* quantification to proton density fat fraction MRI of vertebral bone marrow improves the prediction of osteoporosis.

OBJECTIVES: To assess the predictive value of the combination of bone marrow (BM) proton density fat fraction (PDFF) and liver R2* for osteopenia and osteoporosis and the additional role of liver R2*. METHODS: A total of 107 healthy women were included between June 2019 and January 2021. Each participant underwent dual-energy X-ray absorptiometry (DXA) and chemical shift-encoded 3.0-T MRI. PDFF measurements were performed for each lumbar vertebral body, and R2* measurements were performed in liver segments. Agreement among measurements was assessed by Bland-Altman analysis. Receiver operating characteristic (ROC) curves were generated to select optimised cut-offs for BM PDFF and liver R2*. Univariable and multivariable logistic regressions were performed. The C statistic and continuous net reclassification improvement (NRI) were adopted to explore the incremental predictive ability of liver R2*. RESULTS: Bone mass decreased in 42 cases (39.3%) and nonbone mass decreased in 65 cases (60.7%). There were significant differences among the age groups, menopausal status groups, PDFF > 45.0% groups, and R2* > 67.7 groups. Each measurement had good reproducibility. The odds ratios (95% CIs) were 4.05 (1.22-13.43) for PDFF and 4.34 (1.41-13.35) for R2*. The C statistic (95% CI) without R2* was 0.888 (0.827-0.950), and with R2* was 0.900 (0.841-0.960). The NRI resulting from the combination of PDFF and R2* was 75.6% (p < 0.01). CONCLUSION: The predictive improvement over the use of BM PDFF and other traditional risk factors demonstrates the potential of liver R2* as a biomarker for osteopenia and osteoporosis in healthy women. KEY POINTS: • Liver R2* is a biomarker for the assessment of osteopenia and osteoporosis. • Liver R2* improved the ability to predict osteopenia and osteoporosis. • The intra- and interobserver measurements showed high agreement.

Different impacts of cancer types on cancer screening during COVID-19 pandemic in Taiwan.

BACKGROUND: The COVID-19 pandemic has rapidly become a major challenge for global health care systems and affected other priorities such as the utilization of population-based cancer screening services. We sought to examine to what extent the COVID-19 pandemic has affected cancer screening utilization in Taiwan, even the use of inreach and outreach screening services for different types of cancer screening and different regions. METHODS: Using nationwide cervical, breast, colorectal and oral cancer screening data, the percentage changes in screening participants at inreach and outreach services were calculated and compared between January to April 2020 (COVID-19 pandemic) and January to April 2019. RESULTS: The average percentage change declined from 15% to 40% for cervical, breast, and colorectal cancer screening, with a nearly 50% decline in oral cancer screening. There was a greater preference for breast and colorectal cancer screening outreach services, which had greater accessibility and declined less than inreach services in most regions. The screening utilization varied in different regions, especially in eastern Taiwan where the less convenient transportation and lower risk of COVID-19 transmission had a positive change on four types of cancer screening outreach services. CONCLUSION: The COVID-19 pandemic may have had an effect not only in the utilization of different types of cancer screening but also in the preference between inreach and outreach services, and even in variations in screening services in different regions.

Comprehensive Transcriptomic and Proteomic Analyses Identify a Candidate Gene Set in Cross-Resistance for Endocrine Therapy in Breast Cancer.

Endocrine therapy (ET) of selective estrogen receptor modulators (SERMs), selective estrogen receptor downregulators (SERDs), and aromatase inhibitors (AIs) has been used as the gold standard treatment for hormone-receptor-positive (HR+) breast cancer. Despite its clinical benefits, approximately 30% of patients develop ET resistance, which remains a major clinical challenge in patients with HR+ breast cancer. The mechanisms of ET resistance mainly focus on mutations in the ER and related pathways; however, other targets still exist from ligand-independent ER reactivation. Moreover, mutations in the ER that confer resistance to SERMs or AIs seldom appear in SERDs. To date, little research has been conducted to identify a critical target that appears in both SERMs/SERDs and AIs. In this study, we conducted comprehensive transcriptomic and proteomic analyses from two cohorts of The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) to identify the critical targets for both SERMs/SERDs and AIs of ET resistance. From a treatment response cohort with treatment response for the initial ET regimen and an endocrine therapy cohort with survival outcomes, we identified candidate gene sets that appeared in both SERMs/SERDs and AIs of ET resistance. The candidate gene sets successfully differentiated progress/resistant groups (PD) from complete response groups (CR) and were significantly correlated with survival outcomes in both cohorts. In summary, this study provides valuable clinical implications for the critical roles played by candidate gene sets in the diagnosis, mechanism, and therapeutic strategy for both SERMs/SERDs and AIs of ET resistance for the future.

Effects of Good Pain Management (GPM) ward program on patterns of care and pain control in patients with cancer pain in Taiwan.

BACKGROUND: The undertreatment of cancer pain is a global issue although many international guidelines and various studies bloom to explore the approaches in pain management. However, there is no standard care for cancer pain in routine practices. To set up a standardized procedure for improving cancer pain management in Taiwan, the Good Pain Management (GPM) program is explored to provide treatments following the US National Cancer Care Network (NCCN) Adult Cancer Pain Guideline. METHOD: Patients diagnosed with moderate-to-severe cancer pain were eligible and randomized into the GPM or control arm and observed the first 48 h to evaluate the effects of pain management between 2 arms. Pain control, adequacy of treatments, patient satisfaction, and quality of life (QoL) of eligible patients were analyzed. Ad hoc analyses based on the pain medication category were also conducted. RESULT: Fifty-one patients were enrolled, with 26 and 25 assigned to the GPM and control arms, respectively. Significant differences among the GPM and control arms were found including a greater decrease in the mean numerical rating scale (NRS) score in the GPM arm (- 4.6 vs. - 2.8), a lower proportion of moderate-to-severe pain in the GPM arm (23.2% vs. 39.8%), and a higher pain management index (PMI) score in the GPM arm (0.64 points vs. 0.33 points) (all p < 0.05). Ad hoc analyses revealed that the patient subgroups using strong opioids showed better patient satisfaction in GPM arm when compared with the same subgroup in the control arm. CONCLUSION: In summary, our study demonstrated that the implementation of a standardized pain assessment and management approach (GPM ward program) showed significant improvements on pain relief, decreased the portion of moderate-to-severe cancer pain, and increased patient satisfaction in the 1st 48 h after admission. The implementation of the GPM approach in the cancer ward may provide sooner and better improvement of cancer pain management for patients who suffered moderate-to-severe cancer pain. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT03155516).

Personal Approach to Optimizing Inframammary Fold Incision for Asian Augmentation Mammoplasty.

BACKGROUND: The rates of aesthetic breast augmentation have risen substantially in Asia. Outcomes of various breast augmentation approaches in Asia have not been comprehensively studied. In the past, the inframammary approach to breast augmentation was not popular because of conspicuous scarring. In this article, the authors review academic articles related to the use of an inframammary incision for breast augmentation in Asian women and present our recommendations for the available techniques. METHODS: A literature search was performed for articles published after 2015 on Asian women with augmentation mammoplasty describing techniques, incision sites, outcomes, and complications. The search was performed using the MEDLINE, Embase, and Cochrane databases. We also included our own technique to demonstrate the outcome of augmentation mammoplasty through inframammary incision. RESULTS: Eight articles satisfied our inclusion criteria. Evidence indicates that with proper preoperative design and surgical techniques, scarring resulting from the inframammary approach is not inferior to that resulting from the transaxillary approach in Asian patients. Long-term satisfaction with the inframammary approach to breast augmentation is high in Asian patients.Eight articles reported the outcomes of 1168 women receiving breast augmentation. Inframammary incisions were used in 45.29% of patients (529 patients). After the 2015 publication of Zelken's review paper on Asian breast augmentation, the rate of inframammary incisions increased from 3.1% to 45.29%. CONCLUSIONS: With precise design of the new inframammary fold, accurate wound suture fixation, and postoperative scar care, the inframammary approach to breast augmentation offers optimal operative visualization, reduced pain, fewer complications, and desirable esthetic outcomes even in Asian patients. This study demonstrates that the percentage of inframammary fold approach of Asian esthetic mammoplasty grows rapidly after 2015.

Mediation Effect of Health Beliefs in the Relationship Between Health Knowledge and Uptake of Mammography in a National Breast Cancer Screening Program in Taiwan.

Despite evidence that breast cancer screening effectively diagnoses and treats cancer through early detection, mammography use remains low in Taiwan. We applied the health belief model (HBM) and the knowledge-attitude-behavior (KAB) model as theoretical frameworks to examine factors associated with mammography uptake among women aged 45-69 years in Taiwan. A cross-sectional survey January-July 2018 was conducted of women aged 45-69 years in five southern Taiwan health institutions. Survey questionnaires included demographics, HBM constructs, and health knowledge regarding breast cancer and screening. Multivariable logistic regression models explored the mediation effects of HBM constructs between health knowledge and mammography use. The final analytical sample included 621 women; 67 did not receive mammography and 554 received mammography. When the regression model was adjusted only for demographic factors, women with adequate health knowledge were more likely to undergo mammography (AOR = 2.321, 95%CI = 1.141-3.809); in regression models including health knowledge and HBM constructs, the likelihood effect of health knowledge declined and became insignificant (AOR = 1.711, 95%CI = 0.985-2.972), indicating potential mediation effects between health knowledge and up-to-date mammography use. Overall, based on the HBM and the KAB theoretical framework, our data support that health belief played a substantial mediating role in the association between health knowledge and mammography uptake, in particular perceived barriers and cues to action in the HBM, which were modifying factors of health beliefs. Therefore, to improve mammography uptake, it may be helpful to design educational model-based interventions through tackling those modifiable perceived barriers and enhancing the intensity of external cues to action.

Activation of mitochondrial unfolded protein response is associated with Her2-overexpression breast cancer.

PURPOSE: Mitochondrial unfolding protein are abundant in breast cancer cells, but the mechanism by which breast cancer cells resist apoptosis is still not fully elucidated. In this study, we explored the role of mitochondrial unfolded protein response (mtUPR)-related proteins in four types of breast cancer tissues. METHODS: Mitochondrial fractions were taken from four breast cancer tissues (luminal A, luminal B, Her2 -overexpression, and TNBC) and the expression of mitochondrial polyubiquitinated proteins was observed by western blot and ELISA. In addition, the expression of hsp10, hsp60, and clpp in mitochondria was observed by western blot in breast cancer tissues and adjacent tissues, and confirmed by ELISA. The expression levels of hsp10 and hsp60 were correlated with clinicopathological parameters in 114 breast cancer patients. RESULTS: We found an increase in the performance of mitochondrial polyubiquitinated proteins in breast cancer tissues of luminal A, luminal B, Her2-overexpression, and TNBC. The mitochondrial hsp10, hsp60, and clpp are abundantly expressed in breast cancer tissues rather than adjacent noncancerous tissues. The expression levels of mitochondrial hsp10 and hsp60 were highest in histological grade 3 breast cancer tissues. Additionally, mitochondria with high hsp60 expression were more present in Her2-positive tumors. CONCLUSIONS: We observed that mtUPR was specifically activated in breast cancer tissues but inactivated in normal mammary tissue. MtUPR had also exhibited a particular increase in Her2-overexpression tumors but not in ER- or PR-positive tumors. Taken together, we suggested that mtUPR may act as a potential candidate for developing novel Her2-overexpression breast cancer therapy.

Effects of number of quantum wells and Shockley-Read-Hall recombination in deep-ultraviolet light-emitting diodes.

Effects of the number of quantum wells (QWs) and Shockley-Read-Hall (SRH) recombination in deep-ultraviolet (DUV) light-emitting diodes (LEDs) are investigated theoretically. Simulation results show that, for DUV LEDs with high crystalline quality, light output power increases with an increasing number of QWs. As for the DUV LEDs with poor crystalline quality, light output power may decrease with an increasing number of QWs due to the deteriorated SRH recombination. The injection current density is also an important factor regarding the impact of the number of QWs. When operated at low current density, for the DUV LED with poor crystalline quality, light output power may decrease with an increasing number of QWs.

Humanized bispecific antibody (mPEG × HER2) rapidly confers PEGylated nanoparticles tumor specificity for multimodality imaging in breast cancer.

BACKGROUND: Developing a universal strategy to improve the specificity and sensitivity of PEGylated nanoaparticles (PEG-NPs) for assisting in the diagnosis of tumors is important in multimodality imaging. Here, we developed the anti-methoxypolyethylene glycol (mPEG) bispecific antibody (BsAb; mPEG × HER2), which has dual specificity for mPEG and human epidermal growth factor receptor 2 (HER2), with a diverse array of PEG-NPs to confer nanoparticles with HER2 specificity and stronger intensity. RESULT: We used a one-step formulation to rapidly modify the nanoprobes with mPEG × HER2 and optimized the modified ratio of BsAbs on several PEG-NPs (Lipo-DiR, SPIO, Qdot and AuNP). The αHER2/PEG-NPs could specifically target MCF7/HER2 cells (HER2++) but not MCF7/neo1 cells (HER2+/-). The αHER2/Lipo-DiR and αHER2/SPIO could enhance the sensitivity of untargeted PEG-NPs on MCF7/HER2 (HER2++). In in vivo imaging, αHER2/Lipo-DiR and αHER2/SPIO increased the specific targeting and enhanced PEG-NPs accumulation at 175% and 187% on 24 h, respectively, in HER2-overexpressing tumors. CONCLUSION: mPEG × HER2, therefore, provided a simple one-step formulation to confer HER2-specific targeting and enhanced sensitivity and contrast intensity on HER2 positive tumors for multimodality imaging.

[Infection Control: The Roles and Functions of Nurses Working at the International Medical Center].

Travelers are known to convey infectious diseases across international borders. After its experience with SARS, Taiwan established a comprehensive mechanism at its border to prevent the entry of infectious diseases. However, people with chronic infectious diseases, carriers with no symptoms, and those likely to be infected are not easy to identify during border screenings. Therefore, Taiwan must implement internal disease-containment measures in addition to stopping infectious disease at its borders. With increasing numbers of patients coming to Taiwan for medical examinations, medical aesthetic treatments, and medical treatments and care, the risk of acute, chronic, and contagious diseases originating from non-residents must be considered and addressed. This article was developed to discuss the role and importance of nurses in preventing transnational infectious diseases from the perspective of international medical care. In addition to showing rich nursing experience, sensitivity, and conducting the management and communication of international cases, it is also necessary to make good use of information tools for remote screening care. Taking the period of the COVID-19 outbreak as an example, several procedures have been conducted. First, online detailed history of infectious diseases and nursing evaluations are conducted before admission. Second, preparation and movement notifications are given before admission. Third, online health education and follow-up care as well as cross-unit communication and coordination are implemented. International medical nurses directly affect the quality and effectiveness of international medical treatment. As Taiwan builds up its brand as an international medical caring destination, nursing professionals should help further this trend and announce to the world: Taiwan can help! Nursing can help!

Effect of eribulin on patients with metastatic breast cancer: multicenter retrospective observational study in Taiwan.

PURPOSE: The aim of this study was to confirm the therapeutic role of eribulin on Taiwanese women with metastatic breast cancer. METHODS: This retrospective study examined 449 females who received eribulin between March 2014 and June 2017 at 14 hospitals in Taiwan for treatment of locally advanced or metastatic breast cancer. RESULTS: The survival rate at 24 months was 57.2% (95% CI 51.0-62.9%) and the median time to treatment failure (TTF) was 3.91 months (95% CI 3.45-3.94). A total of 175 patients (40.1%) received eribulin for fewer than 90 days and the others received it for 90 days or more. Eight patients (1.83%) had complete remission, 82 (18.8%) had partial remission, 202 (46.3%) had stable disease, and 144 (33.0%) had progressive disease (PD). Patients' tumors with the luminal A subtype had a significantly better objective response rate. Kaplan-Meier analysis indicated that hormone receptor positivity, luminal A subtype, receipt of eribulin as the 1st to 3rd line therapy, and metastasis to fewer than 4 organs were significantly associated with longer TTF. Stepwise multivariate analysis showed that only receipt of eribulin as the 1st to 3rd line therapy was significantly associated with TTF (HR 1.49, p < 0.001). All toxicities were manageable and only 18 patients (4.1%) discontinued treatment due to adverse events. CONCLUSIONS: Eribulin appears to have better efficacy and cause fewer adverse events, especially neutropenia, in Taiwanese women than Western women.

Altered monocyte differentiation and macrophage polarization patterns in patients with breast cancer.

BACKGROUND: Macrophage heterogeneity is the main feature of the tumour microenvironment. Breast cancer is one of the most life-threatening cancers. However, macrophage polarization patterns in different tumour stages and the importance of its relationship to human epidermal growth factor receptor 2 (HER2) in breast cancer remains highly unclear. The present study investigated the patterns of monocyte differentiation and macrophage polarization in breast cancer. METHODS: Patients with breast cancer (n = 48) and healthy controls (n = 39) were prospectively recruited. The percentages and subsets of circulating macrophage-like cells were analysed by flow cytometry, and the polarization patterns of these cells in the peripheral blood of patients with breast cancer were compared with those of healthy controls. In addition, macrophage polarization patterns in different stages and HER2 status in breast cancer were investigated. RESULTS: The percentages of circulating macrophages, which are defined as PM-2 K+ cells in the peripheral blood, were significantly higher in patients with breast cancer than in healthy controls. The percentages of M1-like macrophages were significantly lower, but those of M2-like macrophages were significantly higher in patients with breast cancer than in healthy controls. The percentage of M2c-like macrophages was significantly higher in advanced (stages II and III) breast cancer. However, the patterns of macrophage polarization were not associated with HER2 status in breast cancer. CONCLUSIONS: Aberrant macrophage polarization was observed in breast cancer and was correlated with breast cancer stage. These quantitative data may provide new molecular biomarkers and potential therapeutic targets in breast cancer.

Enhancement Effect of a Variable Topology of a Membrane-Tethered Anti-Poly(ethylene glycol) Antibody on the Sensitivity for Quantifying PEG and PEGylated Molecules.

Sensitive quantification of the pharmacokinetics of poly(ethylene glycol) (PEG) and PEGylated molecules is critical for PEGylated drug development. Here, we developed a sensitive sandwich enzyme-linked immunosorbent assay (ELISA) for PEG by tethering an anti-PEG antibody (AGP3) via tethers with different dimensions on the surface of 293T cells (293T/S-αPEG, short-type cells; 293T/L-αPEG, long-type cells; 293T/SL-αPEG, hybrid-type cells) to improve the binding capacity and detection limit for free PEG and PEGylated molecules. The binding capacity of hybrid-type cells for PEG-like molecules (CH3-PEG5K-FITC (FITC = fluorescein isothiocyanate) and eight-arm PEG20K-FITC) was at least 10-80-fold greater than that of 293T cells expressing anti-PEG antibodies with uniform tether lengths. The detection limit of free PEG (OH-PEG3K-NH2 and CH3-PEG5K-NH2) and PEG-like molecule (CH3-PEG5K-FITC, CH3-PEG5K-SHPP, and CH3-PEG5K-NIR797) was14-137 ng mL-1 in the hybrid-type cell-based sandwich ELISA. 293T/SL-αPEG cells also had significantly higher sensitivity for quantification of a PEGylated protein (PegIntron) and multiarm PEG macromolecules (eight-arm PEG20K-NH2 and eight-arm PEG40K-NH2) at 3.2, 16, and 16 ng mL-1, respectively. Additionally, the overall binding capacity of 293T/SL-αPEG cells for PEGylated macromolecules was higher than that of 293T/S-αPEG or 293T/L-αPEG cells. Anchoring anti-PEG antibodies on cells via variable-length tethers for cell-based sandwich ELISA, therefore, provides a sensitive, high-capacity method for quantifying free PEG and PEGylated molecules.

Monolithic stacked blue light-emitting diodes with polarization-enhanced tunnel junctions.

Monolithic stacked InGaN light-emitting diode (LED) connected by a polarization-enhanced GaN/AlN-based tunnel junction is demonstrated experimentally in this study. The typical stacked LEDs exhibit 80% enhancement in output power compared with conventional single LEDs because of the repeated use of electrons and holes for photon generation. The typical operation voltage of stacked LEDs is higher than twice the operation voltage of single LEDs. This high operation voltage can be attributed to the non-optimal tunneling junction in stacked LEDs. In addition to the analyses of experimental results, theoretical analysis of different schemes of tunnel junctions, including diagrams of energy bands, diagrams of electric fields, and current-voltage relation curves, are investigated using numerical simulation. The results shown in this paper demonstrate the feasibility in developing cost-effective and highly efficient tunnel-junction LEDs.