Inclusion Effect of Various Levels of Jack Mackerel Meal in Olive Flounder (Paralichthys olivaceus) Diets Substituting 50% Fish Meal with Duck By-Product Meal on Growth and Feed Utilization.

This experiment was performed to evaluate the inclusion impact of various levels of jack mackerel meal (JMM) in olive flounder (P. olivaceus) feeds substituting 50% FM by duck by-product meal (DBM) on growth, feed availability, and economic efficiency. Seven experimental diets were prepared. The control (Con) diet contained 60% FM. Fifty percent FM in the Con diet was substituted with DBM, and then the graded levels (0%, 10%, 20%, 30%, 40%, and 50%) of JMM were added instead of FM, named the DJ0, DJ10, DJ20, DJ30, DJ40, and DJ50 diets, respectively. All feeds were assigned to triplicate fish groups. At the end of 56 days' feeding, fish fed the DJ40 and DJ50 diets exhibited comparable weight gain and specific growth rate to fish fed the Con diet. Higher feed consumption was observed in fish fed the Con, DJ40, and DJ50 diets compared to fish fed the DJ0 and DJ10 diets. Lower feed conversion ratio was observed in fish fed the Con diet compared to fish fed the DJ0, DJ10, DJ20, and DJ30 diets. Furthermore, the DJ50 diet led to the highest economic profit index (EPI). In conclusion, inclusion of 50% JMM in the olive flounder diet replacing 50% FM with DBM seems to be the most recommendable dietary treatment based on growth and feed consumption of olive flounder and EPI.

Mapping High-Risk Arteries Using Doppler Ultrasound for Forehead Contouring in Korean Patients.

BACKGROUND: Forehead flatness is common in Korean populations, and one of the most straightforward techniques for adding volume and achieving a concave forehead is injecting hyaluronic acid (HA) filler. However, definitive guidelines for this procedure are lacking, and careful attention to the arterial anatomy is required to avoid vascular complications. OBJECTIVE: The authors aimed to establish guidelines for performing forehead augmentation using Doppler ultrasound to identify vasculature before HA injection. METHODS AND MATERIALS: Arterial mapping of the faces of 34 patients was performed using Doppler ultrasound. Each anatomic layer (skin, subcutaneous fat, and galea aponeurotica) of the forehead with blood vessels was identified. An average volume of 2.85 mL of HA filler was injected. Postoperative complications, such as infection, hematoma, bruising, nodules, skin necrosis, and blindness, were evaluated. RESULTS: Using Doppler ultrasound, the authors successfully traced all 3 blood vessels (supraorbital, supratrochlear, and frontal branch of the superficial temporal arteries) and avoided them during HA injection. None of the patients experienced arterial complications. CONCLUSION: Doppler ultrasound proves to be an effective technique for arterial mapping, enabling the identification and avoidance of the major blood vessels of the forehead before HA filler injection.

Comparative analysis of obstetric, perinatal, and neurodevelopmental outcomes following chorionic villus sampling and amniocentesis.

Background: The risks of invasive prenatal tests are reported in previous studies such as miscarriage, fetal anomalies, and bleeding. However, few compare short-term and long-term outcomes between invasive tests. This study aims to investigate obstetric, perinatal, and children's neurodevelopmental outcomes following chorionic villus sampling (CVS) or amniocentesis in singleton pregnancy. Methods: This retrospective cohort study included healthy singleton pregnancies underwent transabdominal CVS (gestational age [GA] at 10-13 weeks) or amniocentesis (GA at 15-21 weeks) at a single medical center between 2012 and 2022. Only cases with normal genetic results were eligible. Short-term and long-term neurodevelopmental outcomes were evaluated. Results: The study included 200 CVS cases and 498 amniocentesis cases. No significant differences were found in body mass index, parities, previous preterm birth, conception method, and cervical length (CL) before an invasive test between the groups. Rates of preterm labor, preterm premature rupture of the membranes, preterm birth, neonatal survival, neonatal short-term morbidities, and long-term neurodevelopmental delay were similar. However, the CVS group had a higher rate of cervical cerclage due to short CL before 24 weeks (7.0%) compared to the amniocentesis group (2.4%). CVS markedly increased the risk of cervical cerclage due to short CL (adjusted odd ratio [aOR] = 3.17, 95%CI [1.23-8.12], p = 0.016), after considering maternal characteristics. Conclusion: Performing CVS resulted in a higher incidence of cerclage due to short cervix or cervical dilatation compared to amniocentesis in singleton pregnancies. This highlights the importance of cautious selection for CVS and the necessity of informing women about the associated risks beforehand.

Interplay of valley, layer and band topology towards interacting quantum phases in moiré bilayer graphene.

In Bernal-stacked bilayer graphene (BBG), the Landau levels give rise to an intimate connection between valley and layer degrees of freedom. Adding a moiré superlattice potential enriches the BBG physics with the formation of topological minibands - potentially leading to tunable exotic quantum transport. Here, we present magnetotransport measurements of a high-quality bilayer graphene-hexagonal boron nitride (hBN) heterostructure. The zero-degree alignment generates a strong moiré superlattice potential for the electrons in BBG and the resulting Landau fan diagram of longitudinal and Hall resistance displays a Hofstadter butterfly pattern with a high level of detail. We demonstrate that the intricate relationship between valley and layer degrees of freedom controls the topology of moiré-induced bands, significantly influencing the energetics of interacting quantum phases in the BBG superlattice. We further observe signatures of field-induced correlated insulators, helical edge states and clear quantizations of interaction-driven topological quantum phases, such as symmetry broken Chern insulators.

Sialyllactose supplementation enhances sialylation of Fc-fusion glycoprotein in recombinant Chinese hamster ovary cell culture.

Sialylation during N-glycosylation plays an important role in the half-life of therapeutic glycoproteins in vivo and has sparked interest in the production of therapeutic proteins using recombinant Chinese hamster ovary (rCHO) cells. To improve the sialylation of therapeutic proteins, we examined the effect of sialyllactose supplementation on sialylation of Fc-fusion glycoproteins produced in rCHO cells. Two enzymatically-synthesized sialyllactoses, 3'-sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL), were administered separately to two rCHO cell lines producing the same Fc-fusion glycoprotein derived from DUKX-B11 and DG44, respectively. Two sialyllactoses successfully increased sialylation of Fc-fusion glycoprotein in both cell lines, as evidenced by isoform distribution, sialylated N-glycan formation, and sialic acid content. Increased sialylation by adding sialyllactose was likely the result of increased amount of intracellular CMP-sialic acid (CMP-SA), the direct nucleotide sugar for sialylation. Furthermore, the degree of sialylation enhanced by sialyllactoses was slightly effective or nearly similar compared with the addition of N-acetylmannosamine (ManNAc), a representative nucleotide sugar precursor, to increase sialylation of glycoproteins. The effectiveness of sialyllactose was also confirmed using three commercially available CHO cell culture media. Taken together, these results suggest that enzymatically-synthesized sialyllactose represents a promising candidate for culture media supplementation to increase sialylation of glycoproteins in rCHO cell culture.

Daily station-level records of air temperature, snow depth, and ground temperature in the Northern Hemisphere.

Air temperature (Ta), snow depth (Sd), and soil temperature (Tg) are crucial variables for studying the above- and below-ground thermal conditions, especially in high latitudes. However, in-situ observations are frequently sparse and inconsistent across various datasets, with a significant amount of missing data. This study has assembled a comprehensive dataset of in-situ observations of Ta, Sd, and Tg for the Northern Hemisphere (higher than 30°N latitude), spanning 1960-2021. This dataset encompasses metadata and daily data time series for 27,768, 32,417, and 659 gages for Ta, Sd, and Tg, respectively. Using the ERA5-Land reanalysis data product, we applied deep learning methodology to reconstruct the missing data that account for 54.5%, 59.3%, and 74.3% of Ta, Sd, and Tg daily time series, respectively. The obtained high temporal resolution dataset can be used to better understand physical phenomena and relevant mechanisms, such as the dynamics of land-surface-atmosphere energy exchange, snowpack, and permafrost.

Decoding Upconversion-Emitting Phase in Complex Composites Through Single-Particle-Level Upconversion Imaging and Density Functional Theory Calculations.

The crystal structure and phase stability of a host lattice plays an important role in efficient upconversion phenomena. In stable hosts, lanthanides doping should not generally change the crystal structure of the host itself. But when phase of a system drastically changes after lanthanide doping resulting in multiple phases, accurate identification of upconverting phase remains a challenge. Herein, an attempt to synthesize lanthanide-doped NiMoO4 by microwave hydrothermal method produced MoO3/Yb2Mo4O15/NiMoO4 micro-nano composite upconversion phosphor. A combined approach of density functional theory (DFT) calculations and single-particle-level upconversion imaging has been employed to elucidate the phase stability of different phases and upconversion properties within the composite. Through single-particle-level imaging under 980 nm excitation, an unprecedented resolution in visualizing individual emitting and non-emitting regions within the composite has been achieved, thereby allowing to accurately assign the Yb2Mo4O15 as a sole upconversion emitting phase in the composite. Result of the DFT calculation further shows that the Yb2Mo4O15 phase is the most thermodynamically preferred over other lanthanide-doped phases in the composite. This comprehensive understanding not only advances the knowledge of upconversion emission from composite materials but also holds promise for tailoring optical properties of materials for various applications, including bioimaging, sensing, and photonics, where controlled light emission is crucial.

Structure-Based De Novo Design for the Discovery of Miniprotein Inhibitors Targeting Oncogenic Mutant BRAF.

Being a component of the Ras/Raf/MEK/ERK signaling pathway crucial for cellular responses, the VRAF murine sarcoma viral oncogene homologue B1 (BRAF) kinase has emerged as a promising target for anticancer drug discovery due to oncogenic mutations that lead to pathway hyperactivation. Despite the discovery of several small-molecule BRAF kinase inhibitors targeting oncogenic mutants, their clinical utility has been limited by challenges such as off-target effects and suboptimal pharmacological properties. This study focuses on identifying miniprotein inhibitors for the oncogenic V600E mutant BRAF, leveraging their potential as versatile drug candidates. Using a structure-based de novo design approach based on binding affinity to V600E mutant BRAF and hydration energy, 39 candidate miniprotein inhibitors comprising three helices and 69 amino acids were generated from the substructure of the endogenous ligand protein (14-3-3). Through in vitro binding and kinase inhibition assays, two miniproteins (63 and 76) were discovered as novel inhibitors of V600E mutant BRAF with low-micromolar activity, with miniprotein 76 demonstrating a specific impediment to MEK1 phosphorylation in mammalian cells. These findings highlight miniprotein 76 as a potential lead compound for developing new cancer therapeutics, and the structural features contributing to its biochemical potency against V600E mutant BRAF are discussed in detail.

Neonatal head circumference to maternal mid-transverse pelvic distance ratio as a key anatomical predictor for dystocia: Retrospective case-control study.

OBJECTIVE: This study aimed to examine maternal and neonatal factors in cesarean deliveries due to dystocia, including cephalopelvic disproportion, latent-phase prolongation, and fetal malposition or malpresentation. Additionally, we sought to compare the differences between the dystocia subgroups. METHOD AND MATERIALS: This retrospective case-control study included women who delivered between January 2010 and June 2021 after 37 weeks of pregnancy and underwent abdominal-pelvic CT scans within 5 years before and after delivery. Neonatal factors were extracted from medical charts immediately after delivery. RESULTS: Among the 292 women studied, those with cesarean deliveries for dystocia were older (mean ± SD, 34.2 ± 4.27 vs. 32.2 ± 3.8, p-value = 0.002), had higher pre-pregnancy BMI (22.7 ± 3.67 vs. 21.4 ± 3.48, p-value = 0.012) and term-BMI (27.4 ± 3.72 vs. 25.9 ± 3.66, p-value = 0.010), shorter interspinous distance (ISD, the distance between ischial spine) (10.8 ± 0.76 vs. 11.2 ± 0.85 cm, p-value = 0.003), and longer head circumference (HC) (35 ± 1.47 vs. 34.4 ± 1.36 cm, p-value = 0.003) compared to those who had vaginal deliveries. Univariate logistic regression for dystocia revealed associations between HC/maternal height and HC/ISD ratios (OR, 2.02 [95% confidence interval, CI, 1.4 ~ 2.92], 12.13 [3.2 ~ 46.04], respectively). Multivariate logistic analysis indicated that maternal age, ISD, and HC were significant factors for dystocia (OR, 1.11 [95% CI, 1.01 ~ 1.21], 0.49 [0.26 ~ 0.91], 1.53 [1.07 ~ 2.19], respectively). The subgroup with latent-phase prolongation exhibited the lowest birthweight/term-BMI ratio (124 ± 18.8 vs. 113 ± 10.3 vs. 134 ± 19.1, p-value = 0.013). CONCLUSION: The HC/ISD ratio emerged as a crucial predictor of dystocia, suggesting that reducing term-BMI could potentially mitigate latent-phase prolongation. Further research assessing the maternal mid-pelvis during pregnancy and labor is warranted, along with efforts to reduce BMI during pregnancy.

Effects of post-exercise intake of exogenous lactate on energy substrate utilization at rest.

PURPOSE: This study investigated the effects of exogenous lactate intake on energy metabolism during 1 h of rest after acute exercise. METHODS: Eight-week-old ICR mice were randomly divided into four groups: SED (no treatment), EXE (exercise only), LAC (post-exercise oral lactate administration), and SAL (post-exercise saline administration) (n=8 per group). The exercise intensity was at VO2max 80% at 25 m/min and 15° slope for 50 min. After acute exercise, the LAC and SAL groups ingested lactate and saline orally, respectively, and were allowed to rest in a chamber. Energy metabolism was measured for 1 h during the resting period. RESULTS: LAC and SAL group mice ingested lactate and saline, respectively, after exercise and the blood lactate concentration was measured 1 h later through tail blood sampling. Blood lactate concentration was not significantly different between the two groups. Energy metabolism measurements under stable conditions revealed that the respiratory exchange ratio in the LAC group was significantly lower than that in the SAL group. Additionally, carbohydrate oxidation in the LAC group was significantly lower than that in the SAL group at 10-25 min. No significant difference was observed in the fat oxidation level between the two groups. CONCLUSION: We found that post-exercise lactate intake modified the respiratory exchange ratio after 1 h of rest. In addition, acute lactate ingestion inhibits carbohydrate oxidation during the post-exercise recovery period.

Effects of public transportation use on non-exercise activity thermogenesis and health promotion: a mini-review.

PURPOSE: Public transportation (PT) systems significantly shape urban mobility and have garnered attention owing to their potential impact on public health, particularly the promotion of physical activity. Beyond their transportation functions, PT systems also affect daily energy expenditure through non-exercise activity thermogenesis (NEAT). This mini-review surveys the existing literature to explore the effects of PT use on NEAT levels and subsequent health outcomes. METHODS: A comprehensive literature search was conducted using the electronic databases PubMed, Google Scholar, and Web of Science. Keywords including "public transportation," "non-exercise activity thermogenesis," "physical activity," "health promotion," and related terms were used to identify relevant studies. RESULTS: This review highlights the multifaceted relationship between PT use and health promotion, emphasizing the potential benefits and challenges of increasing NEAT through public transit utilization. Overall, the findings suggest that PT use contributes positively to NEAT levels, and thus improves health outcomes. However, the extent of this impact may vary depending on individual and contextual factors. CONCLUSION: Interventions promoting active transportation modes, including public transit, hold promise for addressing sedentary behavior and fostering healthier lifestyles at the population level.

The complete mitochondrial genome of the ice krill Euphausia crystallorophias Holt & Tattersall, 1906 (Euphausiacea, Euphausiidae), from the Ross Sea, Antarctica.

The mitogenome of Euphausia crystallorophias collected from the Ross Sea Region Marine Protected Area (RSR MPA) is described for the first time. The assembled mitogenome was 17,291 bp in length and consisted of two ribosomal RNAs (rRNAs), 22 transfer RNAs (tRNAs), 13 protein-coding genes (PCGs), and noncoding regions, all of which were identical to those of other euphausiid species. The most common start codon for the 13 PCGs was ATG, and the most common termination codon was TAA. The overall G + C content was 33.2% in the heavy strand. Euphausia crystallorophias was sister to E. superba in the phylogenetic analysis. The mitogenome of E. crystallorophias provided significant DNA molecular data for further identification and phylogenetic analysis within the euphausiids.

Concurrent Optimizations of Efficacy and Blood-Brain Barrier Permeability in New Macrocyclic LRRK2 Inhibitors for Potential Parkinson's Disease Therapeutics.

The elevated activity of leucine-rich repeat kinase 2 (LRRK2) is implicated in the pathogenesis of Parkinson's disease (PD). The quest for effective LRRK2 inhibitors has been impeded by the formidable challenge of crossing the blood-brain barrier (BBB). We leveraged structure-based de novo design and developed robust three-dimensional quantitative structure-activity relationship (3D-QSAR) models to predict BBB permeability, enhancing the likelihood of the inhibitor's brain accessibility. Our strategy involved the synthesis of macrocyclic molecules by linking the two terminal nitrogen atoms of HG-10-102-01 with an alkyl chain ranging from 2 to 4 units, laying the groundwork for innovative LRRK2 inhibitor designs. Through meticulous computational and synthetic optimization of both biochemical efficacy and BBB permeability, 9 out of 14 synthesized candidates demonstrated potent low-nanomolar inhibition and significant BBB penetration. Further assessments of in vitro and in vivo effectiveness, coupled with pharmacological profiling, highlighted 8 as the promising new lead compound for PD therapeutics.

Fish Meal Substitution Effects with the Combined Animal Proteins in the Feeds of Olive Flounder (Paralichthys olivaceus) on Growth Performance, Feed Availability, and Disease Resistance against Streptococcus iniae.

This study aims to reveal the substitution impact of fish meal (FM) with the combined meat meal and chicken by-product meal (CMC) in the olive flounder (P. olivaceus) feeds on growth and feed availability. Seven experimental feeds were formulated. The control (CMC0) diet included 65% FM. In the CMC0 diet, the various (10%, 20%, 40%, 60%, 80%, and 100%) levels of FM were replaced with CMC, named as the CMC10, CMC20, CMC40, CMC60, CMC80, and CMC100 diets, respectively. The total number of 525 juvenile fish (9.2 ± 0.01 g; mean ± SD) was placed into 21 50-L flow-through tanks (25 juveniles/tank) with three replicates. Fish were hand-fed to apparent satiation for 8 weeks. After the 8-week feeding experiment, olive flounder fed the CMC10 (40.0 ± 0.60 g/fish, 2.99 ± 0.021%/day, and 39.57 ± 0.542 g/fish; mean ± SD), CMC20 (47.3 ± 2.58 g/fish, 3.24 ± 0.082%/day, and 45.16 ± 0.760 g/fish), and CMC40 (40.2 ± 1.17 g/fish, 3.00 ± 0.040%/day, and 39.43 ± 0.930 g/fish) diets attained superior (p < 0.0001 for all) weight gain, specific growth rate (SGR), and feed consumption compared to olive flounder fed the CMC0 (35.1 ± 0.96 g/fish, 2.81 ± 0.039%/day, and 33.75 ± 0.544 g/fish), CMC60 (31.7 ± 1.62 g/fish, 2.66 ± 0.068%/day, and 31.60 ± 1.080 g/fish), CMC80 (24.7 ± 0.63 g/fish, 2.33 ± 0.033%/day, and 25.27 ± 0.689 g/fish), and CMC100 (17.8 ± 0.32 g/fish, 1.92 ± 0.021%/day, and 18.99 ± 0.592 g/fish, respectively) diets. Weight gain, SGR, and feed consumption of olive flounder fed the CMC60 diet were comparable to olive flounder fed the CMC0 diet. Feed efficiency and protein efficiency ratio of olive flounder fed the CMC60 diet (1.02 ± 0.007 and 1.79 ± 0.034) were comparable to fish fed the CMC0 diet (1.04 ± 0.012 and 1.85 ± 0.021, respectively). None of the plasma and serum measurements, proximate composition, amino acid profiles, or survival of olive flounder after S. iniae infection were influenced by dietary treatments. In conclusion, CMC can substitute FM up to 60% (39% FM protein in the diet) without deteriorating growth performance, feed availability, or the survival of fish after S. iniae infection.

Controlled Molecular Arrangement of Cinnamic Acid in Layered Double Hydroxide through pi-pi Interaction for Controlled Release.

Cinnamic acid (CA) was successfully incorporated into Zn-Al layered double hydroxide (LDH) through coprecipitation. The CA moiety was stabilized in the interlayer space through not only electrostatic interaction but also intermolecular π-π interaction. It was noteworthy that the CA arrangement was fairly independent of the charge density of LDH, showing the important role of the layer-CA and CA-CA interactions in molecular stabilization. Computer simulations using the Monte Carlo method as well as analytical approaches including infrared, UV-vis spectroscopy, and differential scanning calorimetry showed the existence of intermolecular interaction. In order to reinforce molecular stabilization, a neutral derivative of CA, cinnamaldehyde (CAD), was additionally incorporated into LDH. It was clearly shown that CAD played a role as a π-π interaction mediator to enhance the stabilization of CA. The time-dependent release of CA from LDH was first governed by the layer charge density of LDH; however, the existence of CAD provided additional stabilization to the CA arrangement to slow down the release kinetics.

Chronic Administration of Exogenous Lactate Increases Energy Expenditure during Exercise through Activation of Skeletal Muscle Energy Utilization Capacity in Mice.

We compared the effects of chronic exogenous lactate and exercise training, which influence energy substrate utilization and body composition improvements at rest and during exercise, and investigated the availability of lactate as a metabolic regulator. The mice were divided into four groups: CON (sedentary + saline), LAC (sedentary + lactate), EXE (exercise + saline), and EXLA (exercise + lactate). The total experimental period was set at 4 weeks, the training intensity was set at 60-70% VO2max, and each exercise group was administered a solution immediately after exercise. Changes in the energy substrate utilization at rest and during exercise, the protein levels related to energy substrate utilization in skeletal muscles, and the body composition were measured. Lactate intake and exercise increased carbohydrate oxidation as a substrate during exercise, leading to an increased energy expenditure and increased protein levels of citrate synthase and malate dehydrogenase 2, key factors in the TCA(tricarboxylic acid) cycle of skeletal muscle. Exercise, but not lactate intake, induced the upregulation of the skeletal muscle glucose transport factor 4 and a reduction in body fat. Hence, chronic lactate administration, as a metabolic regulator, influenced energy substrate utilization by the skeletal muscle and increased energy expenditure during exercise through the activation of carbohydrate metabolism-related factors. Therefore, exogenous lactate holds potential as a metabolic regulator.

Inter-scanner super-resolution of 3D cine MRI using a transfer-learning network for MRgRT.

Objective. Deep-learning networks for super-resolution (SR) reconstruction enhance the spatial-resolution of 3D magnetic resonance imaging (MRI) for MR-guided radiotherapy (MRgRT). However, variations between MRI scanners and patients impact the quality of SR for real-time 3D low-resolution (LR) cine MRI. In this study, we present a personalized super-resolution (psSR) network that incorporates transfer-learning to overcome the challenges in inter-scanner SR of 3D cine MRI.Approach: Development of the proposed psSR network comprises two-stages: (1) a cohort-specific SR (csSR) network using clinical patient datasets, and (2) a psSR network using transfer-learning to target datasets. The csSR network was developed by training on breath-hold and respiratory-gated high-resolution (HR) 3D MRIs and their k-space down-sampled LR MRIs from 53 thoracoabdominal patients scanned at 1.5 T. The psSR network was developed through transfer-learning to retrain the csSR network using a single breath-hold HR MRI and a corresponding 3D cine MRI from 5 healthy volunteers scanned at 0.55 T. Image quality was evaluated using the peak-signal-noise-ratio (PSNR) and the structure-similarity-index-measure (SSIM). The clinical feasibility was assessed by liver contouring on the psSR MRI using an auto-segmentation network and quantified using the dice-similarity-coefficient (DSC).Results. Mean PSNR and SSIM values of psSR MRIs were increased by 57.2% (13.8-21.7) and 94.7% (0.38-0.74) compared to cine MRIs, with the reference 0.55 T breath-hold HR MRI. In the contour evaluation, DSC was increased by 15% (0.79-0.91). Average time consumed for transfer-learning was 90 s, psSR was 4.51 ms per volume, and auto-segmentation was 210 ms, respectively.Significance. The proposed psSR reconstruction substantially increased image and segmentation quality of cine MRI in an average of 215 ms across the scanners and patients with less than 2 min of prerequisite transfer-learning. This approach would be effective in overcoming cohort- and scanner-dependency of deep-learning for MRgRT.

Exosome-Coated Prussian Blue Nanoparticles for Specific Targeting and Treatment of Glioblastoma.

Glioblastoma is one of the most aggressive and invasive types of brain cancer with a 5-year survival rate of 6.8%. With limited options, patients often have poor quality of life and are moved to palliative care after diagnosis. As a result, there is an extreme need for a novel theranostic method that allows for early diagnosis and noninvasive treatment as current peptide-based delivery standards may have off-target effects. Prussian Blue nanoparticles (PBNPs) have recently been investigated as photoacoustic imaging (PAI) and photothermal ablation agents. However, due to their inability to cross the blood-brain barrier (BBB), their use in glioblastoma treatment is limited. By utilizing a hybrid, biomimetic nanoparticle composed of a PBNP interior and a U-87 cancer cell-derived exosome coating (Exo:PB), we show tumor-specific targeting within the brain and selective thermal therapy potential due to the strong photoconversion abilities. Particle characterization was carried out and showed a complete coating around the PBNPs that contains exosome markers. In vitro cellular uptake patterns are similar to native U-87 exosomes and when exposed to an 808 nm laser, show localized cell death within the specified region. After intravenous injection of Exo:PB into subcutaneously implanted glioblastoma mice, they have shown effective targeting and eradication of tumor volume compared to PEG-coated PBNPs (PEG:PB). Through systemic administration of Exo:PB particles into orthotopic glioblastoma-bearing mice, the PBNP signal was detected in the brain tumor region through PAI. It was seen that Exo:PB had preferential tumor accumulation with less off-targeting compared to the RGD:PB control. Ex vivo analysis validated specific targeting with a direct overlay of Exo:PB with the tumor by both H&E staining and Ki67 labeling. Overall, we have developed a novel biomimetic material that can naturally cross the BBB and act as a theranostic agent for systemic targeting of glioblastoma tissue and photothermal therapeutic effect.

Targeted Biodegradable Near-Infrared Fluorescent Nanoparticles for Colorectal Cancer Imaging.

Colorectal cancer (CRC) is the third leading cause of cancer death in the U.S., and early detection and diagnosis are essential for effective treatment. Current methods are inadequate for rapid detection of early disease, revealing flat lesions, and delineating tumor margins with accuracy and molecular specificity. Fluorescence endoscopy can generate wide field-of-view images enabling detection of CRC lesions and margins; increased signal intensity and improved signal-to-noise ratios can increase both speed and sensitivity of cancer detection. For this purpose, we developed targeted near-infrared (NIR) fluorescent silica nanoparticles (FSNs). We tuned their size to 50-200 nm and conjugated their surface with an antibody to carcinoembryonic antigen (CEA) to prepare CEA-FSNs. The physicochemical properties and biodegradable profiles of CEA-FSN were characterized, and molecular targeting was verified in culture using HT29 (CEA positive) and HCT116 (CEA negative) cells. CEA-FSNs bound to the HT29 cells to a greater extent than to the HCT116 cells, and smaller CEA-FSNs were internalized into HT29 cells more efficiently than larger CEA-FSNs. After intravenous administration of CEA-FSNs, a significantly greater signal was observed from the CEA-positive HT29 than the CEA-negative HCT116 tumors in xenografted mice. In F344-PIRC rats, polyps in the intestine were detected by white-light endoscopy, and NIR fluorescent signals were found in the excised intestinal tissue after topical application of CEA-FSNs. Immunofluorescence imaging of excised tissue sections demonstrated that the particle signals coregistered with signals for both CRC and CEA. These results indicate that CEA-FSNs have potential as a molecular imaging marker for early diagnosis of CRC.