Improving cell reinfusion to enhance the efficacy of chimeric antigen receptor T-cell therapy and alleviate complications.

Adoptive cell therapy (ACT) is a rapidly expanding area within the realm of transfusion medicine, focusing on the delivery of lymphocytes to trigger responses against tumors, viruses, or inflammation. This area has quickly evolved from its initial promise in immuno-oncology during preclinical trials to commercial approval of chimeric antigen receptor (CAR) T-cell therapies for leukemia and lymphoma (Jun and et al., 2018) [1]. CAR T-cell therapy has demonstrated success in treating hematological malignancies, particularly relapsed/refractory B-cell acute lymphoblastic leukemia and non-Hodgkin's lymphoma (Qi and et al., 2022) [2]. However, its success in treating solid tumors faces challenges due to the short-lived presence of CAR-T cells in the body and diminished T cell functionality (Majzner and Mackall, 2019) [3]. CAR T-cell therapy functions by activating immune effector cells, yet significant side effects and short response durations remain considerable obstacles to its advancement. A prior study demonstrated that the therapeutic regimen can induce systemic inflammatory reactions, such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), tumor lysis syndrome (TLS), off-target effects, and other severe complications. This study aims to explore current research frontiers in this area.

Comparative analysis of vestibular endolymphatic hydrops grading methods and hearing loss in Ménière's disease: a retrospective MRI study using 3D-real inversion recovery sequence.

PURPOSE: To compare the correlation between different grading methods of vestibular endolymphatic hydrops (EH) and the severity of hearing loss in Ménière's disease (MD), and evaluate the diagnostic value of these methods in diagnosing MD. METHODS: This retrospective study included 30 patients diagnosed with MD from June 2021 to August 2023. All patients underwent inner ear MR gadolinium-enhanced imaging using three-dimensional (3D)-real inversion recovery sequences and pure-tone audiometry. The EH levels were independently evaluated according to the classification methods outlined by Nakashima et al. (Acta Otolaryngol Suppl 5-8, 2009. https://doi.org/10.1080/00016480902729827 ) (M1), Fang et al. (J Laryngol Otol 126:454-459, 2012. https://doi.org/10.1017/S0022215112000060 ) (M2), Barath et al. (Am J Neuroradiol 35:1387-1392, 2014. https://doi.org/10.3174/ajnr.A3856 ), (M3), Liu et al. (Front Surg 9:874971, 2022. https://doi.org/10.3389/fsurg.2022.874971 ), (M4), and Bernaerts et al. (Neuroradiology 61:421-429, 2019. https://doi.org/10.1007/s00234-019-02155-7 ) (M5), with a subsequent comparison of interobserver agreement. After achieving a consensus, an analysis was performed to explore the correlations between vestibular EH grading using different methods, the average hearing thresholds at low-mid, high-, and full frequencies and clinical stages. The diagnostic capabilities of these methods for MD were then compared. RESULTS: The interobserver consistency of M2-M5 was superior to that of M1. The EH grading based on M4 showed a significant correlation with the average hearing thresholds at low-mid, high-, and full frequencies and clinical stages. M1, M2, M3, and M5 correlated with some parameters. A receiver operating characteristic curve analysis indicated that M5 significantly outperformed M1, M2, M3, and M4 in terms of diagnostic efficiency for MD. CONCLUSION: M4 showed the strongest correlation with the degree of hearing loss in patients with MD, whereas M5 showed the highest diagnostic performance.

Probabilistic activity driven model of temporal simplicial networks and its application on higher-order dynamics.

Network modeling characterizes the underlying principles of structural properties and is of vital significance for simulating dynamical processes in real world. However, bridging structure and dynamics is always challenging due to the multiple complexities in real systems. Here, through introducing the individual's activity rate and the possibility of group interaction, we propose a probabilistic activity-driven (PAD) model that could generate temporal higher-order networks with both power-law and high-clustering characteristics, which successfully links the two most critical structural features and a basic dynamical pattern in extensive complex systems. Surprisingly, the power-law exponents and the clustering coefficients of the aggregated PAD network could be tuned in a wide range by altering a set of model parameters. We further provide an approximation algorithm to select the proper parameters that can generate networks with given structural properties, the effectiveness of which is verified by fitting various real-world networks. Finally, we construct the co-evolution framework of the PAD model and higher-order contagion dynamics and derive the critical conditions for phase transition and bistable phenomenon using theoretical and numerical methods. Results show that tendency of participating in higher-order interactions can promote the emergence of bistability but delay the outbreak under heterogeneous activity rates. Our model provides a basic tool to reproduce complex structural properties and to study the widespread higher-order dynamics, which has great potential for applications across fields.

FGF19-Based Mini Probe Targeting FGFR4 for Diagnosis and Surgical Navigation of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a frequent malignancy that has a high death rate and a high rate of recurrence following surgery, owing to insufficient surgical resection. Furthermore, HCC is prone to peritoneal metastasis (HCC-PM), resulting in a significant number of tiny cancer lesions, making surgical removal more challenging. As a potential imaging target, FGFR4 is highly expressed in tumors, especially in HCC, but is less expressed in the normal liver. In this study, we used computational simulation approaches to develop peptide I0 derived from FGF19, a particular ligand of FGFR4, and labeled it with the NIRF dye, MPA, for HCC detection. In surgical navigation, the TBR was 9.31 ± 1.36 and 8.57 ± 1.15 in HepG2 in situ tumor and HCC-PM models, respectively, indicating considerable tumor uptake. As a result, peptide I0 is an excellent clinical diagnostic reagent for HCC, as well as a tool for surgically resecting HCC peritoneal metastases.

The preferential utilization of hepatic glycogen as energy substrates in largemouth bass (Micropterus salmoides) under short-term starvation.

To elucidate the underlying mechanism of the energy metabolism in largemouth bass (Micropterus salmoides), cultured fish (initial body weight: 77.57 ± 0.75 g) in the present study were starved for 0 h, 12 h, 24 h, 48 h, 96 h and 192 h, respectively. The proximate composition analysis showed that short-term starvation induced a significant up-regulation in crude protein proportion in hepatic of cultured fish (P < 0.05). However, short-term starvation significantly decreased the hepatosomatic index and the viscerosomatic index of cultured fish (P < 0.05). The exact hepatic glycogen content in the group starved for 92 h presented remarkable decrease (P < 0.05). Meanwhile, compared with the weight change of lipid and protein (mg) in hepatic (y = 0.0007x2 - 0.2827x + 49.402; y = 0.0013x2 - 0.5666x + 165.31), the decreasing trend of weight in glycogen (mg) was more pronounced (y = 0.0032x2 - 1.817x + 326.52), which suggested the preferential utilization of hepatic glycogen as energy substrates under short-term starvation. Gene expression analysis revealed that the starvation down-regulated the expression of insulin-like growth factor 1 and genes of TOR pathway, such as target of rapamycin (tor) and ribosomal protein S6 (s6) (P < 0.05). In addition, the starvation significantly enhanced expression of lipolysis-related genes, including hormone-sensitive lipase (hsl) and carnitine palmitoyl transferase I (cpt1), but down-regulated lipogenesis as indicated by the inhibited expression of fatty acids synthase (fas), acetyl-CoA carboxylase 1 (acc1) and acetyl-CoA carboxylase 2 (acc2) (P < 0.05). Starvation of 24 h up-regulated the expression of glycolysis genes, glucokinase (gk), phosphofructokinase liver type (pfkl) and pyruvate kinase (pk), and then their expression returned to the normal level. Meanwhile, the expression of gluconeogenesis genes, such as glucose-6-phosphatase catalytic subunit (g6pc), fructose-1,6-bisphosphatase-1 (fbp1) and phosphoenolpyruvate carboxy kinase (pepck), was significantly inhibited with the short-term starvation (P < 0.05). In conclusion, short-term starvation induced an overall decline in growth performance, but it could deplete the hepatic glycogen accumulation and mobilize glycogen for energy effectively.

Development of a novel EphA2-targeting radioligand for SPECT imaging in different tumor models.

The erythropoietin-producing hepatoma A2 receptor (EphA2) is a tyrosine kinase, which is overexpressed in tumors while having lower expression in normal tissues, making it an excellent target for tumor diagnosis and treatment. Peptide radiotracers offer unique advantages in tumor diagnosis and therapy and have been approved for clinical use. In this study, a high-affinity EPHA2-targeted radiotracer, 99mTc-HYNIC-PEG4-EPH-3, was developed and designed based on linear peptides. 99mTc-HYNIC-PEG4-EPH-3 exhibited superior water solubility and stability. And 99mTc-HYNIC-PEG4-EPH-3 could specifically target EphA2-expressing tumors, particularly with a tumor-to-non-target (T/NT) ratio >4.7 excluding kidneys. As a result of excellent biodistribution and tumor targeting capability of 99mTc-HYNIC-PEG4-EPH-3, it might be a promising candidate drug for clinical diagnosis of EphA2-overexpressing tumors.

Core self-evaluation and innovative behavior: mediating effect of error orientation and self-efficacy of nurses.

Background: Innovation plays a crucial role in advancing nursing and healthcare. Despite its significance, there is a paucity of research examining the interplay among nursing innovative behavior, core self-evaluation, error orientation, and self-efficacy. This study, grounded in Bandura's social cognitive theory, seeks to not only investigate the influence of core self-evaluation on nurses' innovative behavior but also to elucidate the mediating roles of error orientation and self-efficacy within this relationship. By addressing these dynamics, the research aims to provide a comprehensive understanding of the factors shaping nurses' innovative behaviors and contribute to the broader discourse on enhancing healthcare practices. Design: A cross-sectional study using an online questionnaire. Setting: Participants were recruited from 23 hospitals in 6 provinces and 1 municipality directly under the central government in China, namely Zhejiang, Anhui, Jiangxi, Guangdong, Hebei, Henan, and Shanghai. Participants: A total of 741 nurses enrolled in the study. Methods: The participants completed the nurse innovative behavior scale, the core self-evaluation scale, the error orientation questionnaire, and the self-efficacy scale online in 2023. SPSS and AMOS were used for data analysis. The reporting followed the STROBE checklist. Results: A total of 706 valid questionnaires were collected. A positive core self-evaluation was associated with more innovative behavior, and this relation was partially mediated by error orientation and self-efficacy to avoid failure. Core self-evaluation, error orientation and self-efficacy of nurses had a positive predictive effect on innovation behavior, with the path coefficients at 0.09, 0.23, and 0.39, respectively. Conclusion: Our study complements the evidence on the mechanism of action between the core self-evaluation and innovative behavior. Our findings have important clinical implications for promoting innovative behavior in nurses.

Traumatic intestinal ischemic necrosis.

A 71-year-old male patient presented to our emergency department with a 1-day history of abdominal pain after an accidental fall. Laboratory test results were as follows: a white blood cell count of 2.32 × 109/L, blood lactate of 3.0 mmol/L, pH 7.30, calcitonin precursor level of 71.09 ng/ml, and creatinine of 115 umol/L. The abdominal CT revealed: portal vein gas accumulation (PVGA) accompanied by a fluid-air level; pneumatosis cystoides intestinalis (PCI) manifested as multiple gas collections within the wall of the lower small intestine. Based on lowered blood pH and elevated lactate levels, there was a high suspicion of small intestinal ischemic necrosis. Subsequent emergency laparotomy and pathological examination confirmed necrosis of the small intestine.

Evaluation of the relationship between endolymphatic hydrops and hearing loss in Meniere's disease based on three-dimensional real inversion recovery sequence

Abstract Objectives: The degree of endolymphatic hydrops in Meniere's disease may be related to hearing loss. However, the results of prior studies have been inconsistent. We aimed to investigate the relationship between endolymphatic hydrops and hearing loss characteristics in Meniere's disease. Methods: This study included 54 patients (62 ears) with Meniere's disease. Patients underwent three-dimensional real inversion recovery sequences for magnetic resonance imaging and puretone audiometry. Endolymphatic hydrops were assessed according to Gurkov's criteria (2011). Correlations between different degrees of endolymphatic hydrops and pure-tone audiometry, as well as staging, were analysed. Results: Pure tone audiometry and staging were higher for vestibular endolymphatic hydrops complicated by cochlear ones than isolated cochlear or vestibular hydrops (both p<0.05). There was no significant correlation between vestibular endolymphatic hydrops and pure-tonal audiometry or staging (all p > 0.05). The degree of hydrops in the middle turn was correlated with the mid-frequency hearing threshold (p<0.05). The degree of cochlear hydrops was correlated with the audiometry, low-frequency hearing thresholds, mid-frequency hearing thresholds and staging (p<0.01). Conclusion: The types and sites of endolymphatic hydrops based on a 3D-real inversion recovery sequence can be used to indicate the degree of hearing loss in patients with Meniere's disease. Level of evidence: Level III.

Evaluation of the relationship between endolymphatic hydrops and hearing loss in Meniere's disease based on three-dimensional real inversion recovery sequence.

OBJECTIVES: The degree of endolymphatic hydrops in Meniere's disease may be related to hearing loss. However, the results of prior studies have been inconsistent. We aimed to investigate the relationship between endolymphatic hydrops and hearing loss characteristics in Meniere's disease. METHODS: This study included 54 patients (62 ears) with Meniere's disease. Patients underwent three-dimensional real inversion recovery sequences for magnetic resonance imaging and pure-tone audiometry. Endolymphatic hydrops were assessed according to Gurkov's criteria (2011). Correlations between different degrees of endolymphatic hydrops and pure-tone audiometry, as well as staging, were analysed. RESULTS: Pure tone audiometry and staging were higher for vestibular endolymphatic hydrops complicated by cochlear ones than isolated cochlear or vestibular hydrops (both p < 0.05). There was no significant correlation between vestibular endolymphatic hydrops and pure-tonal audiometry or staging (all p > 0.05). The degree of hydrops in the middle turn was correlated with the mid-frequency hearing threshold (p < 0.05). The degree of cochlear hydrops was correlated with the audiometry, low-frequency hearing thresholds, mid-frequency hearing thresholds and staging (p < 0.01). CONCLUSION: The types and sites of endolymphatic hydrops based on a 3D-real inversion recovery sequence can be used to indicate the degree of hearing loss in patients with Meniere's disease. LEVEL OF EVIDENCE: Level III.

Novel GRPR-Targeting Peptide for Pancreatic Cancer Molecular Imaging in Orthotopic and Liver Metastasis Mouse Models.

Despite advancements in pancreatic cancer treatment, it remains one of the most lethal malignancies with extremely poor diagnosis and prognosis. Herein, we demonstrated the efficiency of a novel peptide GB-6 labeled with a near-infrared (NIR) fluorescent dye 3H-indolium, 2-[2-[2-[(2-carboxyethyl)thio]-3-[2-[1,3-dihydro-3,3-dimethyl-5-sulfo-1-(3-sulfopropyl)-2H-indol-2-ylidene]ethylidene]-1-cyclohexen-1-yl]ethenyl]-3,3-dimethyl-5-sulfo-1-(3-sulfopropyl)-, inner salt (MPA) and radionuclide technetium-99m (99mTc) as targeting probes using the gastrin-releasing peptide receptor (GRPR) that is overexpressed in pancreatic cancer as the target. A short linear peptide with excellent in vivo stability was identified, and its radiotracer [99mTc]Tc-HYNIC-PEG4-GB-6 and the NIR probe MPA-PEG4-GB-6 exhibited selective and specific uptake by tumors in an SW1990 pancreatic cancer xenograft mouse model. The favorable biodistribution of the tracer [99mTc]Tc-HYNIC-PEG4-GB-6 in vivo afforded tumor-specific accumulation with high tumor-to-muscle and -bone contrasts and renal body clearance at 1 h after injection. The biodistribution analysis revealed that the tumor-to-pancreas and -intestine fluorescence signal ratios were 5.2 ± 0.3 and 6.3 ± 1.5, respectively, in the SW1990 subcutaneous xenograft model. Furthermore, the high signal accumulation in the orthotopic pancreatic and liver metastasis tumor models with tumor-to-pancreas and -liver fluorescence signal ratios of 7.66 ± 0.48 and 3.94 ± 0.47, respectively, enabled clear tumor visualization for intraoperative navigation. The rapid tumor targeting, precise tumor boundary delineation, chemical versatility, and high potency of the novel GB-6 peptide established it as a high-contrast imaging probe for the clinical detection of GRPR, with compelling additional potential in molecular-targeted therapy.

In Vivo Staging the Progression of Colitis and Associated Cancer by Concurrent Microimaging of Key Biomarkers.

Currently colorectal cancer (CRC) staging (colitis, adenoma, and carcinoma) mainly relies on ex vivo pathologic analysis requiring an invasive surgical process with limited sample collection and increased metastatic risk. Thus, in vivo noninvasive pathological diagnosis is extremely demanded. By verifying the samples of clinical patients and CRC mouse models, it was found that vascular endothelial growth factor receptor 2 (VEGFR2) was barely expressed in the colitis stage and only appeared in adenoma and carcinoma stages with obvious elevation, while prostaglandin E receptor 4 (PTGER4) could be observed from colitis to adenoma and carcinoma stages with a gradient increase of expression. VEGFR2 and PTGER4 were further chosen as key biomarkers for molecular pathological diagnosis in vivo and corresponding molecular probes were constructed. The feasibility of in vivo noninvasive CRC staging by concurrent microimaging of dual biomarkers using confocal laser endoscopy (CLE) was verified in CRC mouse models and further confirmed by ex vivo pathological analysis. In vivo CLE imaging exhibited the correlation of severe colonic crypt structural alteration with a higher biomarker expression in adenoma and carcinoma stages. This strategy shows promise in benefiting patients undergoing CRC progression with in-time, noninvasive, and precise pathological staging, thus providing valuable guidance for selecting therapeutic strategies.

Correlation between grading methods of the cochlear endolymphatic hydrops and hearing loss in meniere's disease using three-dimensional real inversion recovery sequences.

BACKGROUND: The grading of intracochlear endolymphatic hydrops (EH) in Meniere's disease (MD) varies and lacks uniformity. AIMS: To compare the grading consistency and correlation between different grade methods of intracochlear EH and hearing loss. MATERIALS AND METHODS: Thirty-one patients diagnosed with MD underwent gadolinium-enhanced magnetic resonance imaging. Two radiologists graded the cochlea EH according to M1, M2, M3, or M4. We analysed the grading consistency and correlation between the EH degrees and hearing loss. RESULTS: The weighted kappa coefficients for inter-observer and intra-observer agreements for grading using M1 were good, whereas those for M2, M3, and M4 are excellent (all p < 0.001). The cochlear EH degree based on M2 was correlated with the low-to-mid frequencies, high frequencies, full frequencies, and MD clinical stage (all p < 0.05). The degrees based on M1, M3, M4 were only relevant to some of the 4 items. CONCLUSIONS: The grading consistency of M2, M3, M4 is relatively higher than that of M1, and M2 shows the strongest correlation with hearing loss. SIGNIFICANCE: Our results provide a more accurate method for assessing the clinical severity of MD.

DNA Framework-Programmed Ligand Positioning to Modulate the Targeting Performance.

Effective targeting of nanomedicine is still an intricacy since unsatisfactory clinical trial feedback demonstrated their inadequate concentration at the desired area. However, the regulatory effect of ligand-modification patterns on the targeting effect has not been surveyed yet. Based on the superior spatial addressability of DNA frame structures, herein DNA tetrahedrons were used as templates for site-specific modification of targeting ligands. In this work, nanovectors with homogeneous ligand-modification patterns, including various valence of ligands and the precisely controlled distance between ligands at the nanoscale, were established for the first time. In vitro and in vivo targeting performance studies found that merely relying on the augment of the ligand quantity exhibited a confined promotion effect on the targeting efficiency. Notably, the space distance between ligands displayed a more important role in reforming the targeting effect, and the largest ligand distance (approximately 156.55 Å) pattern exhibited an optimal targeting effect and prominently cytostatic activity toward tumor cells. Generally, the survey of ligand-modification patterns on nanovectors provided a valid guidance to direct the optimization of nanomedicine.

Esterification catalyzed by an efficient solid acid synthesized from PTSA and UiO-66(Zr) for biodiesel production.

p-Toluenesulfonic acid (PTSA) is a typical homogeneous acid for biodiesel production. Due to the shortcomings of high deliquescence and non-recyclability, it is necessary to synthesize a recyclable solid acid. For the sake of this, UiO-66(Zr) is used to support PTSA through defect coordination, and four different preparation routes are compared. The obtained catalyst (UiO-G) is characterized with thermogravimetry analysis (TG), X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), pyridine FTIR spectroscopy (py-FTIR), nitrogen adsorption-desorption, and base titration. In addition, the effects of esterification parameters on conversion are investigated to obtain the optimal conditions. To further verify the high catalytic activity of UiO-G, the kinetic model of solid-liquid-liquid esterification is established, in which the kinetic parameters of activation energy, reaction order, and exponential factor are calculated. Results indicate the PTSA is successfully inserted in UiO-66(Zr) without destroying its original structure. With that, the maximum conversion of oleic acid to biodiesel of 91.3% is achieved with a molar ratio of methanol/oleic acid of 12 and a catalyst amount of 8 wt% at 70 °C for 2 h. Moreover, UiO-G could remarkably reduce the activation energy, where the activation energy is 28.61 kJ mol-1, the average reaction order is 1.51, and the pre-exponential factor is 29.11 min-1.

Hyaluronic acid-based nanogels derived from multicomponent self-assembly for imaging-guided chemo-photodynamic cancer therapy.

Multifunctional theranostic nanoplatforms integrated of imaging function, multi-modality therapy, stimuli-responsiveness, and targeted delivery are of highly desirable attributes in achieving precise medicine. However, preparation of multifunctional nanoplatforms often involves laborious, multiple steps and inevitably utilizes low-biocompatible or non-functional components. Herein we report a facile, one-step self-assembly strategy to fabricate hyaluronic acid (HA)-based multifunctional tumor theranostic nanoplatform by employing magnetic resonance imaging (MRI) agent Mn2+ as a reversible crosslink agent for histidine-grafted HA, along with simultaneously loading chemotherapeutic agent doxorubicin hydrochloride (DOX) and photodynamic therapy agent chlorin e6, to realize MRI-guided targeted chemo-photodynamic cancer therapy. The targeted delivery and stimuli-responsive payload release were demonstrated in vitro and in vivo. Furthermore, the combined chemo-photodynamic therapy of the nanoassembly dramatically improved the cancer therapeutic outcome, in comparison with that of free DOX and nanoplatform solely loaded DOX in a melanoma bearing mice. Our one step assemble strategy is of great potential in clinic transformation.

Platelet-Mimicking Therapeutic System for Noninvasive Mitigation of the Progression of Atherosclerotic Plaques.

Atherosclerotic plaque is the primary cause of cardiovascular disorders and remains a therapeutic hurdle for the early intervention of atherosclerosis. Traditional clinical strategies are often limited by surgery-related complications or unsatisfactory effects of long-term drug administration. Inspired by the plaque-binding ability of platelets, a biomimic photodynamic therapeutic system is designed to mitigate the progression of atherosclerotic plaques. This system is composed of photosensitizer-loaded upconversion nanoparticle cores entrapped in the platelet membrane. The platelet membrane coating facilitates specific targeting of the therapeutic system to macrophage-derived foam cells, the hallmark, and main component of early stage atherosclerotic plaques, which is firmly confirmed by in vivo fluorescent and single-photon emission computed tomography/computed tomography (SPECT/CT) radionuclide imaging. Importantly, in vivo phototherapy guided by SPECT/CT imaging alleviates plaque progression. Further immunofluorescence analysis reveals foam cell apoptosis and ameliorated inflammation. This biomimic system, which combines plaque-binding with radionuclide imaging guidance, is a novel, noninvasive, and potent strategy to mitigate the progression of atherosclerotic plaque.

Effects of Dietary Phospholipids on Growth Performance, Digestive Enzymes Activity and Intestinal Health of Largemouth Bass (Micropterus salmoides) Larvae.

While the beneficial roles of dietary phospholipids on health status and overall performances of fish larvae have been well demonstrated, the underlying mechanisms remain unclear. To address this gap, the present study was conducted to investigate the effects of dietary phospholipids on growth performance, intestinal development, immune response and microbiota of larval largemouth bass (Micropterus salmoides). Five isonitrogenous and isolipidic micro-diets were formulated to contain graded inclusion levels of phospholipids (1.69, 3.11, 5.23, 7.43 and 9.29%). Results showed that the supplementation of dietary phospholipids linearly improved the growth performance of largemouth bass larvae. The inclusion of dietary phospholipids increased the activity of digestive enzymes, such as lipase, trypsin and alkaline phosphatase, and promoted the expression of tight junction proteins including ZO-1, claudin-4 and claudin-5. Additionally, dietary phospholipids inclusion alleviated the accumulation of intestinal triacylglycerols, and further elevated the activity of lysozyme. Dietary phospholipids inhibited the transcription of some pro-inflammatory cytokines, including il-1ß, and tnf-α, but promoted the expression of anti-inflammatory cytokines tgf-ß, with these modifications being suggested to be mediated by the p38MAPK/Nf-κB pathway. The analysis of bacterial 16S rRNA V3-4 region indicated that the intestinal microbiota profile was significantly altered at the genus level with dietary phospholipids inclusion, including a decreased richness of pathogenic bacteria genera Klebsiella in larval intestine. In summary, it was showed that largemouth bass larvae have a specific requirement for dietary phospholipids, and this study provided novel insights on how dietary phospholipids supplementation contributes to improving the growth performance, digestive tract development and intestinal health.

AT1R-Specific Ligand Angiotensin II as a Novel SPECT Agent for Hepatocellular Carcinoma Diagnosis.

Hepatocellular carcinoma (HCC) is characterized by a high mortality and early diagnosis and treatment are critically needed. Ang II type 1 receptor (AT1R) has recently emerged as a potential molecular target for cancer diagnosis and intervention. Here, we labeled angiotensin II (Ang II), an AT1R ligand that is overexpressed in various solid cancers, with the near-infrared fluorescent dye, MPA, and radionuclide technetium-99m, and evaluated its capacity for HCC detection. These analyses were done in vitro using HepG2 (AT1R-positive) and BxPC3 (AT1R-negative) cell lines, and in vivo using a subcutaneous and orthotopic xenograft mouse model by fluorescence and SPECT imaging. Both Ang II-PEG4-MPA- and [99mTc]Tc-HYNIC-PEG4-Ang II-bound AT1R exhibited a high affinity in vitro and [99mTc]Tc-HYNIC-PEG4-Ang II displayed an acceptable level of in vitro stability in rat plasma and whole blood. In vivo imaging revealed excellent specific tumor-targeting in HepG2 mouse xenografts models. In vitro and in vivo competition experiments revealed specific Ang II-PEG4-MPA and [99mTc]Tc-HYNIC-PEG4-Ang II uptake by HepG2 cells and tumors. Altogether, AT1R-positive tumors were successfully detected via fluorescence and SPECT imaging using Ang II-PEG4-MPA and [99mTc]Tc-HYNIC-PEG4-Ang II, respectively. Given their superior targeting capacity, Ang II-PEG4-MPA and [99mTc]Tc-HYNIC-PEG4-Ang II are promising tools for HCC detection and warrant clinical translation.

GRPR-targeted SPECT imaging using a novel bombesin-based peptide for colorectal cancer detection.

Colorectal cancer (CRC) is the third most common cancer worldwide, and the prognosis of CRC is better with an earlier diagnosis. The presence of the gastrin-releasing peptide receptor (GRPR) has been documented in very high numbers on colorectal cancer cells, which makes it an ideal biomarker for the diagnosis of CRC. Bombesin (BBN) peptide analogs have been extensively investigated for the imaging of human cancers with GRPR overexpression. Recently, we have reported a novel GRPR-targeted peptide named the GB-6 peptide. The GB-6 peptide based on BBN7-14 was designed to improve in vivo metabolic stability and decrease intestinal uptake. Meanwhile, GB-6 greatly retained the original GRPR-binding affinity of BBN7-14. In this study, the GB-6 peptide was labeled with radionuclide 99mTc or fluorescent dye for colorectal cancer imaging. In vitro receptor binding was studied in Caco-2 cells, and the GRPR targeting capacity and kinetics in vivo were evaluated using Caco-2 tumor xenografted mice models. In addition, cells and mice were also subjected to the corresponding BBN7-14 conjugations for comparison. The GB-6 peptide exhibited specific GRPR binding in vitro with a high affinity similar to that of BBN7-14. Furthermore, we observed that GB-6 showed higher tumor uptake and displayed lower intestinal activity than corresponding unmodified probe BBN7-14 in Caco-2 tumor-bearing mice. Overall, our studies demonstrated that GB-6 has the potential for early detection of CRC patients, and it may also serve as a valuable tool for non-invasive monitoring of colorectal tumor growth.