1.3-µm identical active electro-absorption modulated laser with quantum well intermixed passive waveguide.

Quantum well intermixing (QWI) is an effective method for simple and well-defined monolithic integration of photonic devices. We introduce an identical-active electro-absorption modulated laser (IA-EML) with optimized QWI, which is applied to reduce the absorptive waveguide region. To determine the optimal intermixed IA-EML structure, we conduct a comparative analysis between the cases of an IA-EML with only an intermixed waveguide region and with both intermixed waveguide and electro-absorption modulator (EAM) regions, as well as the case without QWI. The results reveal that the intermixed region effectively inhibits the absorption in the waveguide. In particular, the IA-EML with only waveguide intermixing exhibits superior modulation characteristics with low driving voltages and a high extinction ratio. Our work provides an attractive approach for suppressing the absorptive waveguide region in the IA-EML to enhance modulation performance and to develop photonic integrated circuits with a simplified process.

Effectiveness and Safety of Regdanvimab in Patients With Mild-To-Moderate COVID-19: A Retrospective Cohort Study.

BACKGROUND: Regdanvimab has decreased the time to clinical recovery from coronavirus disease 2019 (COVID-19) and lowered the rate of oxygen therapy according to the results from phase 2/3 randomized controlled trial. More information is needed about the effects and safety of regdanvimab. METHODS: We analyzed data for patients with high-risk mild or moderate COVID-19 being admitted to Busan Medical Center between December 1, 2020 and April 16, 2021. A propensity score (PS) matched analysis was conducted to compare patients treated with and without regdanvimab. The primary outcome was in-hospital death or disease aggravation which means the need for oxygen therapy (low- or high-flow oxygen therapy and mechanical ventilation) and secondary outcomes comprised the length of hospital stay and adverse reactions. RESULTS: Among 1,617 selected patients, 970 (60.0%) were indicated for regdanvimab. Of these, 377 (38.9%) were administered with regdanvimab. Among a 1:1 PS-matched cohort of 377 patients each treated with and without regdanvimab, 19 (5%) and 81 (21.5%) reached the composite outcome of death, or disease aggravation, respectively (absolute risk difference, -16.4%; 95% confidence interval [CI], -21.1, -11.7; relative risk difference, 76.5%; P < 0.001). Regdanvimab significantly reduced the composite outcome of death, or disease aggravation in univariate (odds ratio [OR], 0.194; 95% CI, 0.112-0.320; P < 0.001) and multivariable-adjusted analyses (OR, 0.169; 95% CI, 0.095-0.289; P < 0.001). The hospital stay was shorter for the group with than without regdanvimab. Some hematological adverse reactions were more frequent in the group without regdanvimab, but other adverse reactions did not significantly differ between the groups. CONCLUSION: Regdanvimab was associated with a significantly lower risk of disease aggravation without increasing adverse reactions.

pH-Responsive Amphiphilic Polyether Micelles with Superior Stability for Smart Drug Delivery.

Despite widespread interest in the amphiphilic polymeric micelles for drug delivery systems, it is highly desirable to achieve high loading capacity and high efficiency to reduce the side effects of therapeutic agents while maximizing their efficacy. Here, we present a novel hydrophobic epoxide monomer, cyclohexyloxy ethyl glycidyl ether (CHGE), containing an acetal group as a pH-responsive cleavable linkage. A series of its homopolymers, poly(cyclohexyloxy ethyl glycidyl ether)s (PCHGEs), and block copolymers, poly(ethylene glycol)-block-poly(cyclohexyloxy ethyl glycidyl ether)s (mPEG-b-PCHGE), were synthesized via anionic ring-opening polymerization in a controlled manner. Subsequently, the self-assembled polymeric micelles of mPEG-b-PCHGE demonstrated high loading capacity, excellent stability in biological media, tunable release efficiency, and high cell viability. Importantly, quantum mechanical calculations performed by considering prolonged hydrolysis of the acetal group in CHGE indicated that the CHGE monomer had higher hydrophobicity than three other functional epoxide monomer analogues developed. Furthermore, the preferential cellular uptake and in vivo therapeutic efficacy confirmed the enhanced stability and the pH-responsive degradation of the amphiphilic block copolymer micelles. This study provides a new platform for the development of versatile smart polymeric drug delivery systems with high loading efficiency and tailorable release profiles.

Influenza Vaccine Effectiveness in Children at the Emergency Department during the 2018-2019 Season: the First Season School-aged Children Were Included in the Korean Influenza National Immunization Program.

BACKGROUND: For the 2018-2019 season, the national influenza immunization program expanded to cover children aged from 6 months to 12 years in Korea. This study aimed to analyze vaccine effectiveness (VE) against influenza in children visiting the pediatric emergency room at a tertiary hospital during the 2018-2019 season. METHODS: Patients tested for influenza antigens from October 1st 2018 to May 31st 2019 at the pediatric emergency room of Samsung Medical Center were included. Patients' influenza antigen test results, influenza vaccination history, and underlying medical conditions were reviewed retrospectively. VE was estimated from the test-negative design study. RESULTS: Among the 2,901 visits with influenza test results 1,692 visits of 1,417 patients were included for analysis. Among these 1,417 patients, 285 (20.1%) were positive (influenza A, n = 211, 74.0%; influenza B, n = 74, 26.0%). The VE in all patients was 36.4% (95% confidence interval [CI], 13.9 to 53.1). The VE for influenza A was 37.6% (95% CI, 12.6 to 55.5) and VE for influenza B was 24.0% (?38.5 to 58.3). The VE in the age group 6 months to 12 years was significant with a value of 35.6% (95% CI, 10.5 to 53.7); it was not statistically significant in the age group 13 to 18 years. In a multivariate logistic regression model, patients who received an influenza vaccination were less likely to get influenza infection (OR, 0.6; 95% CI, 0.4 to 0.8; P = 0.001), with significant confounding factors such as age group 13 to 18 years (OR, 0.5; 95% CI, 0.3 to 0.8; P = 0.003) and underlying hematology-oncology disease (OR, 0.3; 95% CI, 0.1 to 0.6; P = 0.002). CONCLUSION: We report moderate effectiveness of influenza vaccination in previously healthy children aged from 6 months to 12 years in the 2018-2019 season.

Gastrodia elata Blume and Zanthoxylum schinifolium Siebold & Zucc Mixed Extract Suppress Platelet Aggregation and Thrombosis.

Background and objectives: Blood vessel thrombosis causes blood circulation disorders, leading to various diseases. Currently, various antiplatelet and anticoagulant drugs, such as aspirin, warfarin, heparin, and non-vitamin K antagonist oral anticoagulants (NOACs), are used as the major drugs for the treatment of a wide range of thrombosis. However, these drugs have a side effect of possibly causing internal bleeding due to poor hemostasis when taken for a long period of time. Materials and Methods: Gastrodia elata Blume (GE) and Zanthoxylum schinifolium Siebold & Zucc (ZS) are known to exhibit hemostatic and antiplatelet effects as traditional medicines that have been used for a long time. In this study, we investigated the effect of a mixed extract of GE and ZS (MJGE09) on platelet aggregation and plasma coagulation. Results: We found that MJGE09 inhibited collagen-and ADP-induced platelet aggregation in vitro. In addition, collagen- and ADP-induced platelet aggregation were also inhibited in a dose-dependent manner on the platelets of mice that were orally administered MJGE09 ex vivo. However, compared with aspirin, MJGE09 did not prolong the rat tail vein bleeding time in vivo and did not show a significant effect on the increase in the prothrombin time (PT) and activated partial thromboplastin time (aPTT). Conclusions: These results suggest that MJGE09 can be used as a potential anticoagulant with improved antithrombotic efficacy.

Geographic Variation in Postoperative Imaging for Low-Risk Breast Cancer.

Background: The objective of this study was to examine the presence and magnitude of US geographic variation in use rates of both recommended and high-cost imaging in young patients with early-stage breast cancer during the 18 month period after surgical treatment of their primary tumor. Methods: Using the Truven Health MarketScan Commercial Database, a descriptive analysis was conducted of geographic variation in annual rates of dedicated breast imaging and high-cost body imaging of 36,045 women aged 18 to 64 years treated with surgery for invasive unilateral breast cancer between 2010 and 2012. Multivariate hierarchical analysis examined the relationship between likelihood of imaging and patient characteristics, with metropolitan statistical area (MSA) serving as a random effect. Patient characteristics included age group, BRCA1/2 carrier status, family history of breast cancer, combination of breast surgery type and radiation therapy, drug therapy, and payer type. All MSAs in the United States were included, with areas outside MSAs within a given state aggregated into a single area for analytic purposes. Results: Descriptive analysis of rates of imaging use and intensity within MSA regions revealed wide geographic variation, irrespective of treatment cohort or age group. Increased probability of recommended postoperative dedicated breast imaging was primarily associated with age and treatment including both surgery and radiation therapy, followed by MSA region (odds ratio, 1.42). Increased probability of PET use-a high-cost imaging modality for which postoperative routine use is not recommended in the absence of specific clinical findings-was primarily associated with surgery type followed by MSA region (odds ratio, 1.82). Conclusions: In patients with breast cancer treated for low-risk disease, geography has effects on the rates of posttreatment imaging, suggesting that some patients are not receiving beneficial dedicated breast imaging, and high-cost nonbreast imaging may not be targeted to those groups most likely to benefit.

Isoflurane Postconditioning Inhibits tPA-Induced Matrix Metalloproteinases Activation After Hypoxic Injury via Low-Density Lipoprotein Receptor-Related Protein and Extracellular Signal-Regulated Kinase Pathway.

Tissue plasminogen activator (tPA) is the only recommended pharmacological treatment for acute ischemic stroke. However, tPA can induce intracerebral hemorrhage by blood-brain barrier breakdown through an increase in matrix metalloproteinases (MMPs). Previously, we showed that isoflurane postconditioning reduced intracranial hemorrhage following tPA treatment after cerebral ischemia. Here, we investigated the mechanism by which isoflurane postconditioning reduces tPA-induced MMP-2 and MMP-9 activation following hypoxia/reoxygenation (H/R) in brain endothelial cells. Mouse brain endothelial cells (bEnd.3) were exposed to 6 h of oxygen-glucose deprivation and 3 h of reoxygenation with tPA. Cells were treated with isoflurane for 1 h of the reoxygenation condition and the effect of isoflurane postconditioning on MMP-2 and MMP-9 activation was assessed. Involvement of low-density lipoprotein receptor-related protein (LRP), which is a receptor for tPA, and the extracellular signal-regulated kinase (ERK) and NF-κB pathway in isoflurane postconditioning was assessed using LRP inhibitor (receptor-associated protein, RAP) and ERK-1/2 inhibitor (PD98059). Isoflurane postconditioning decreased tPA-induced MMP-2 and MMP-9 activation under H/R. tPA treatment under H/R increased expression of LRP and the active form of NF-κB. Isoflurane postconditioning suppressed LRP expression, increased ERK-1/2 activation, and suppressed MMP-2 and MMP-9 activation, comparable to the effect of RAP. Activation of ERK-1/2, inhibition of NF-κB activation, and suppression of MMP-2 and MMP-9 activation by isoflurane postconditioning were abolished with PD98059 treatment. These finding indicate that isoflurane postconditioning inhibits tPA-induced MMP-2 and MMP-9 activation following H/R via the LRP/ERK/NF-κB pathway in bEnd.3.

Home Return After Surgery in Patients Aged over 85 Years is Associated with Preoperative Albumin Levels, the Type of Surgery, and APACHE II Score.

BACKGROUND: Owing to an aging society, both the number of operations for patients aged >85 years and the average age of patients admitted to the intensive care unit (ICU) are rapidly increasing. However, mortality is not an appropriate outcome measurement in patients aged >85 years; a more important outcome is home return (HR), because quality of life is valuable to these patients. We identified predictors for HR of patients aged >85 years admitted to the ICU after surgery. METHODS: Retrospective analysis of medical records was conducted at a university hospital. Patients aged > 85 years, admitted to the ICU after surgery from March 2006 to June 2015 (n = 187), were divided into a HR group (patients who returned home after discharge) and non-HR group (deceased or transferred to nursing facilities). Perioperative data and outcome were assessed and compared. Multivariate logistic regression analysis was conducted to identify independent predictors. RESULTS: The average age of patients was 88 years. HR occurred in 61% of patients, and mortality was 9%. The HR group had higher preoperative albumin level than did the non-HR group. More patients in the non-HR group experienced hip surgery than in the HR group (51 vs. 12%, P < 0.001). APACHE II score was higher (P < 0.001) in the non-HR group. In multivariate analysis, preoperative albumin, hip surgery, and APACHE II score were independent predictors of HR. CONCLUSION: Predictors of HR of surgical critically ill elderly patients included preoperative albumin level, hip surgery, and APACHE II score on ICU admission.

An Image-Based Reduction of Metal Artifacts in Computed Tomography.

OBJECTIVE: Various strategies have been developed in the past to reduce the excessive effects of metal artifacts in computed tomography images. From straightforward sinogram inpainting-based methods to computationally expensive iterative methods, all have been successful in improving the image quality up to a certain degree. We propose a novel image-based metal artifact subtraction method that achieves a superior image quality and at the same time provides a quantitatively more accurate image. METHODS: Our proposed method consists of prior image-based sinogram inpainting, metal sinogram extraction, and metal artifact image subtraction. Reconstructing the metal images from the extracted metal-contaminated portions in the sinogram yields a streaky image that eventually can be subtracted from the uncorrected image. The prior image is reconstructed from the sinogram that is free from the metal-contaminated portions by use of a total variation (TV) minimization algorithm, and the reconstructed prior image is fed into the forward projector so that the missing portions in the sinogram can be recovered. Image quality of the metal artifact-reduced images on selected areas was assessed by the structure similarity index for the simulated data and SD for the real dental data. RESULTS: Simulation phantom studies showed higher structure similarity index values for the proposed metal artifact reduction (MAR) images than the standard MAR images. Thus, more artifact suppression was observed in proposed MAR images. In real dental phantom data study, lower SD values were calculated from the proposed MAR images. The findings in real human arm study were also consistent with the results in all phantom studies. Thus, compared with standard MAR images, lesser artifact intensity was exhibited by the proposed MAR images. CONCLUSIONS: From the quantitative calculations, our proposed method has shown to be effective and superior to the conventional approach in both simulation and real dental phantom cases.

Design and performance of 10-Gb/s L-band REAM-SOA for OLT Transmitter in next generation access networks.

We present a 10-Gb/s L-band reflective electro-absorption modulator integrated with a semiconductor optical amplifier (REAM-SOA) having improved transmission performance at very low input power of seed light. To decrease the input power of seed light, the absorption characteristics of the REAM are adjusted to reduce the amplified spontaneous emission light returned into the SOA, suppressing the gain saturation effect of the SOA. At a considerably low input power of -16 dBm, the REAM-SOA exhibits a low transmission penalty of about 1.2 dB after 50-km SMF transmission. Over a wide input power range from -16 dBm to 5 dBm, a penalty of less than 1.6 dB is achieved at 50-km transmission.

Sparse-view computed laminography with a spherical sinusoidal scan for nondestructive testing.

X-ray computed laminography is widely used in nondestructive testing of relatively flat objects using an oblique scanning configuration for data acquisition. In this work, a new scanning scheme is proposed in conjunction with the compressive-sensing-based image reconstruction for reducing imaging radiation dose and scanning time. We performed a numerical study comparing image qualities acquired by various scanning configurations that are practically implementable: single-arc, double-arc, oblique, and spherical-sinusoidal trajectories. A compressive-sensing-inspired total-variation (TV) minimization algorithm was used to reconstruct the images from the data acquired at only 40 projection views in those trajectories. It was successfully demonstrated that the proposed scanning scheme outperforms the others in terms of image contrast and spatial resolution, although the oblique scanning scheme showed a comparable resolution property. We believe that the proposed scanning method may provide a solution to fast and low-dose nondestructive testing of radiation-sensitive and highly integrated devices such as multilayer microelectronic circuit boards.

Special consideration is required for the component-resolved diagnosis of egg allergy in infants.

BACKGROUND: There are few reports regarding differences in reactivity to the major egg allergens according to children's age, although component-resolved diagnosis is gradually being used. OBJECTIVE: To investigate differences in reactivity to major egg allergens among various age groups of children with egg allergy. METHODS: Twenty-seven patients diagnosed with egg allergy were included. Egg allergy was defined as a convincing history of reproducible symptoms within 2 hours of egg consumption and an egg white-specific IgE level of at least 0.35 kUA/L. Patients were divided into 3 age groups: younger than 12 months (group A, 7 subjects), 12 to 23 months (group B, 8 subjects), and at least 24 months (group C, 12 subjects). Immunoblotting and enzyme-linked immunosorbent assay investigated IgE reactivity toward ovalbumin, ovomucoid, and ovotransferrin in eggs. RESULTS: Immunoblotting analysis showed that all patients in group A reacted to ovalbumin, whereas reactions to other proteins were not detected. All patients in group B displayed a reaction to ovalbumin and ovomucoid. IgE binding to ovotransferrin was shown in 3 patients in group B. All patients in group C displayed reactivity to ovalbumin, 5 patients showed a reaction to ovomucoid, and 8 patients displayed a reaction to ovotransferrin. As a patient's age increased, specific IgE binding to ovalbumin and ovotransferrin increased (P = .011 and .004). CONCLUSION: IgE reactivity to egg allergens differs according to children's ages.

[The Effect of Socioeconomic Status to Depression of Perimenopause Women: Pathway Analysis Using the Reserve Capacity Model].

PURPOSE: Based on the Reserve Capacity Model, this study investigated the effects of pre- and postmenopausal women's socioeconomic status (SES) on depression, focusing on the mediating effects of self-esteem, happiness, and family relationship satisfaction with social network relationships. METHODS: This cross-sectional study involved secondary analysis of national data on 771 perimenopause women gathered from the 16th Korea Welfare Panel Study (KOWEPS) 2021. A path analysis model was constructed to evaluate the relationship between SES, social network satisfaction, self-esteem, perceived health status, and depression. Data were analyzed using ADANCO 2.3.1 and Mplus 8.4. RESULTS: Although SES had no direct effect on depression, it did affect depression through self-esteem, happiness, and satisfaction with family relationships. CONCLUSION: The findings of this study indicate that perimenopausal women's personal resources-psychosocial variables such as self-esteem and happiness-had a higher effect on depression than tangible reserves like SES. Therefore, interventions for enhancing self-esteem and happiness may prevent depression in perimenopausal women effectively.

Mitigation of Rayleigh crosstalk using noise suppression technique in 10-Gb/s REAM-SOA.

We demonstrate a mitigation of Rayleigh back-scattering (RBS) impact in 10-Gb/s reflective electroabsorption modulator monolithically integrated with semiconductor optical amplifier (REAM-SOA). The technique is based on the intensity-noise suppression of the centralized incoherent seed-light, which enables smooth evolution of deployed DWDM applications. We exhibit the power penalty of less than 1 dB at the large RBS crosstalk value of about 8 dB when the optical power of seed-light is lowered about -10 dBm.

10-Gb/s direct modulation of polymer-based tunable external cavity lasers.

We demonstrate a directly-modulated 10-Gb/s tunable external cavity laser (ECL) fabricated by using a polymer Bragg reflector and a high-speed superluminescent diode (SLD). The tuning range and output power of this ECL are measured to be >11 nm and 2.6 mW (@ 100 mA), respectively. We directly modulate this laser at 10 Gb/s and transmit the modulated signal over 20 km of standard single-mode fiber. The power penalty is measured to be <2.8 dB at the bit-error rate (BER) of 10(-10).

Constraints on the use of lifespan-shortening Wolbachia to control dengue fever.

Dengue fever, a viral disease spread by the mosquito Aedes aegypti, affects 50-100 million people a year in many tropical countries. Because the virus must incubate within mosquito hosts for two weeks before being able to transmit the infection, shortening the lifespan of mosquitoes may curtail dengue transmission. We developed a continuous time reaction-diffusion model of the spatial spread of Wolbachia through a population of A. aegypti. This model incorporates the lifespan-shortening effects of Wolbachia on infected A. aegypti and the fitness advantage to infected females due to cytoplasmic incompatibility (CI). We found that local establishment of the Wolbachia infection can occur if the fitness advantage due to CI exceeds the fitness reduction due to lifespan-shortening effects, in accordance with earlier results concerning fecundity reduction. However, spatial spread is possible only if the fitness advantage due to CI is twice as great as the fitness reduction due to lifespan shortening effects. Moreover, lifespan-shortening and fecundity-reduction can have different effects on the speed of wave-retreat. Using data from the literature, we estimated all demographic parameters for infected and uninfected mosquitoes and computed the velocities of spread of infection. Our most optimistic estimates suggest that the spatial spread of lifespan-shortening Wolbachia may be so slow that efficient spatial spread would require a prohibitively large number of point releases. However, as these estimates of demographic parameters may not accurately reflect natural conditions, further research is necessary to corroborate these predictions.

Tumor-targeting oxidative stress nanoamplifiers as anticancer nanomedicine with immunostimulating activity.

Compared to normal cells, cancer cells are more susceptible to insults of prooxidants that generate ROS (reactive oxygen species) or scavenge antioxidants such as glutathione (GSH). Cancer cells undergo immunogenic cell death (ICD) by elevated oxidative stress. Herein, we report rationally designed F-ssPBCA nanoparticles as a tumor-targeting prooxidant, which generates ROS and scavenges GSH simultaneously to cooperatively amplify oxidative stress, leading to ICD. Prooxidant F-ssPBCA nanoparticles are composed of a disulfide-bridged GSH scavenging dimeric prodrug (ssPB) that self-assembles to form nanoconstructs and encapsulates ROS-generating BCA (benzoyloxy cinnamaldehyde). F-ssPBCA nanoparticles significantly elevate oxidative stress to kill cancer cells and also evoke ICD featured by the release of CRT (calreticulin), HMGB-1 (high mobility group box-1), and adenosine triphosphate (ATP). Animal studies revealed that F-ssPBCA nanoparticles accumulate in tumors preferentially and suppress tumor growth effectively. The results of this study demonstrate that prooxidant-mediated oxidative stress elevation is a highly effective strategy to kill cancer cells selectively and even evoke abundant ICD. We anticipate that oxidative stress amplifying F-ssPBCA nanoparticles hold tremendous translational potential as a tumor targeted ICD-inducing anticancer nanomedicine.

Cross-scale dynamics and the evolutionary emergence of infectious diseases.

When emerging pathogens encounter new host species for which they are poorly adapted, they must evolve to escape extinction. Pathogens experience selection on traits at multiple scales, including replication rates within host individuals and transmissibility between hosts. We analyze a stochastic model linking pathogen growth and competition within individuals to transmission between individuals. Our analysis reveals a new factor, the cross-scale reproductive number of a mutant virion, that quantifies how quickly mutant strains increase in frequency when they initially appear in the infected host population. This cross-scale reproductive number combines with viral mutation rates, single-strain reproductive numbers, and transmission bottleneck width to determine the likelihood of evolutionary emergence, and whether evolution occurs swiftly or gradually within chains of transmission. We find that wider transmission bottlenecks facilitate emergence of pathogens with short-term infections, but hinder emergence of pathogens exhibiting cross-scale selective conflict and long-term infections. Our results provide a framework to advance the integration of laboratory, clinical, and field data in the context of evolutionary theory, laying the foundation for a new generation of evidence-based risk assessment of emergence threats.

Tumor-Targeting H2O2-Responsive Photosensitizing Nanoparticles with Antiangiogenic and Immunogenic Activities for Maximizing Anticancer Efficacy of Phototherapy.

Phototherapy including photothermal therapy (PTT) and photodynamic therapy (PDT) uses photosensitizers and light to kill cancer cells and has become a promising therapeutic modality because of advantages such as minimal invasiveness and high cancer selectivity. However, PTT or PDT as a single treatment modality has insufficient therapeutic efficacy. Moreover, oxygen consumption by PDT activates angiogenic factors and leads to cancer recurrence and progression. Therefore, the therapeutic outcomes of phototherapy would be maximized by employing photosensitizers for concurrent PTT and PDT and suppressing angiogenic factors. Therefore, integrating photosensitive agents and antiangiogenic agents in a single nanoplatform would be a promising strategy to maximize the therapeutic efficacy of phototherapy. In this study, we developed hyaluronic acid-coated fluorescent boronated polysaccharide (HA-FBM) nanoparticles as a combination therapeutic agent for phototherapy and antiangiogenic therapy. Upon a single near-infrared laser irradiation, HA-FBM nanoparticles generated heat and singlet oxygen simultaneously to kill cancer cells and also induced immunogenic cancer cell death. Beside their fundamental roles as photosensitizers, HA-FBM nanoparticles exerted antiangiogenic effects by suppressing the vascular endothelial growth factor (VEGF) and cancer cell migration. In a mouse xenograft model, intravenously injected HA-FBM nanoparticles targeted tumors by binding CD44-overexpressing cancer cells and suppressed angiogenic VEGF expression. Upon laser irradiation, HA-FBM nanoparticles remarkably eradicated tumors and increased anticancer immunity. Given their synergistic effects of phototherapy and antiangiogenic therapy from tumor-targeting HA-FBM nanoparticles, we believe that integrating the photosensitizers and antiangiogenic agents into a single nanoplatform presents an attractive strategy to maximize the anticancer therapeutic efficacy of phototherapy.

Diagnosis and Simultaneous Treatment of Musculoskeletal Injury Using H2O2-Triggered Echogenic Antioxidant Polymer Nanoparticles in a Rat Model of Contusion Injury.

Ultrasound is clinically used for diagnosis and interventions for musculoskeletal injuries like muscle contusion, but contrast of ultrasonography still remains a challenge in the field of the musculoskeletal system. A level of hydrogen peroxide (H2O2) is known to be elevated during mechanical tissue damage and therefore H2O2 can be exploited as a diagnostic and therapeutic marker for mechanical injuries in the musculoskeletal system. We previously developed poly(vanillin-oxalate) (PVO) as an inflammation-responsive polymeric prodrug of vanillin, which is designed to rapidly respond to H2O2 and exert antioxidant and anti-inflammatory activities. The primary aim of this study is to verify whether PVO nanoparticles could serve as contrast agents as well as therapeutic agents for musculoskeletal injuries simultaneously. In a rat model of contusion-induced muscle injury, PVO nanoparticles generated CO2 bubbles to enhance the ultrasound contrast in the injury site. A single intramuscular injection of PVO nanoparticles also suppressed contusion-induced muscle damages by inhibiting the expression of pro-inflammatory cytokines and inflammatory cell infiltration. We, therefore, anticipate that PVO nanoparticles have great translational potential as not only ultrasound imaging agents but also therapeutic agents for the musculoskeletal disorders such as contusion.