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Adoptive cellular therapy (ACT) using memory-like (ML) natural killer (NK) cells, generated through overnight ex vivo activation with IL-12, IL-15, and IL-18, has shown promise for treating hematologic malignancies. We recently reported that a multifunctional fusion molecule, HCW9201, comprising IL-12, IL-15, and IL-18 domains could replace individual cytokines for priming human ML NK cell programming ("Prime" step). However, this approach does not include ex vivo expansion, thereby limiting the ability to test different doses and schedules. Here, we report the design and generation of a multifunctional fusion molecule, HCW9206, consisting of human IL-7, IL-15, and IL-21 cytokines. We observed > 300-fold expansion for HCW9201-primed human NK cells cultured for 14 days with HCW9206 and HCW9101, an IgG1 antibody, recognizing the scaffold domain of HCW9206 ("Expand" step). This expansion was dependent on both HCW9206 cytokines and interactions of the IgG1 mAb with CD16 receptors on NK cells. The resulting "Prime and Expand" ML NK cells exhibited elevated metabolic capacity, stable epigenetic IFNG promoter demethylation, enhanced antitumor activity in vitro and in vivo, and superior persistence in NSG mice. Thus, the "Prime and Expand" strategy represents a simple feeder cell-free approach to streamline manufacturing of clinical-grade ML NK cells to support multidose and off-the-shelf ACT. [ABSTRACT FROM AUTHOR]

The stability and dispersion of Copper (Cu) powders in an aqueous medium impacts their performances. Thus the Cu powder suspensions were prepared by adding different stabilizers—sodium dodecyl sulfate (SDS), sodium dodecylbenzene sulfonate (SDBS), polyvinyl pyrrolidone (PVP), and hexadecyl trimethyl ammonium bromide (CTAB); the best surfactant was selected and its stability and dispersion were studied. The study systematically examined the effect of the stability of suspensions via sedimentation analysis, including solid–liquid ratio, the concentration of stabilizer, and dispersion time. The particle size, the stability of suspensions, phase composition, and microstructure of Cu powders were characterized by laser particle size analyzer, zeta potential, X-ray diffraction (XRD), transmission electron microscope (TEM), and scanning electron microscope (SEM). The results indicate that the stability of the suspension is improved with the addition of PVP due to the steric hindrance of PVP, and the growth and agglomeration of particles are retarded by the formation of a thick hydration layer with the optimizing concentrations, dispersion time, and solid–liquid ratio 10 g/L, 30 min, and 1:25, respectively. [ABSTRACT FROM AUTHOR]

Sports injuries have been a common concern during athlete training as the number of Chinese athletes and their training intensity have increased. These injuries frequently impact critical locations, including the waist, shoulder, and wrist, impeding training progress and intensity. Inadequate training levels, a lack of understanding of preventive measures, inappropriate movements, insufficient warm-up exercises, low physical condition, and an inability to adjust to the environment all contribute to sports injuries. As a result, athlete training and recovery suffer. To address these issues, this study presents a neural network-based sports injury risk analysis system that uses blockchain and the Internet of Things (IoT). The suggested system combines a multi-sensor data fusion technique based on blockchain and IoT to evaluate and analyze sports injuries completely. The system has three unique roles: coach, team doctor, and athlete, each with its functional modules. Sensors collect data on athletes' recovery from sports injuries by collecting and analyzing inputs inside the human action system. The system then establishes the output values of a neural network and a risk level table, allowing for the estimation of athletes' risk levels based on the given table. Comparing the traditional technique and the sports injury rehabilitation monitoring system demonstrates that the technology can reliably detect players' injury locations in as little as 0.2 s. Furthermore, a thorough examination of the system's tracking and analysis accuracy reveals a recovery rate of approximately 94.39%, demonstrating minimal fluctuations and improved stability. The experimental findings reveal that combining blockchain, IoT, and neural network technologies makes the proposed sports injury rehabilitation monitoring system useful in quickly recognizing damage positions and enabling accurate tracking and analysis. [ABSTRACT FROM AUTHOR]

The aim was to develop a model to predict the adult height (AH) of idiopathic central precocious puberty (ICPP) girls who underwent gonadotropin-releasing hormone analog (GnRHa) treatment. Data analysis included 258 girls with ICPP. Among them, 101 girls who reached final AH (FAH) with GnRHa treatment were analyzed to verify three previous prediction models and develop a unique model based on multiple linear regression. The control group consisted of 41 untreated ICPP girls. Moreover, 116 girls treated with GnRHa who almost attained FAH were included for external validation. Based on our cohorts, all of the three previously published models underestimated the FAH with an R of 0.667, 0.793, and 0.664. The AH prediction model was built as follows: Calculated AH (cm) = 1.89630 * Height SDS + 2.29927 * Height SDS for bone age + 0.40776 * Target height + 100.16684 (R2 = 0.66 and adjusted R2 = 0.65). Internal validation showed a mean root mean squared error (RMSE) of 2.16 cm and a mean absolute error (MAE) of 1.64 cm. External validation showed that a significant error (> 1 SD) appeared only in 7 of 116 girls (6.0%). The model is displayed on the website: http://cpppredict.shinyapps.io/dynnomapp. Conclusion: A model for predicting the AH of girls with ICPP was developed incorporating the variables of height SDS, height SDS for bone age, and target height. The internal and external validation ensures an appropriate degree of discrimination and calibration of the prediction model. What is Known: • Uncertainty prevails as how to predict the adult height of patients with central precocious puberty following gonadotropin-releasing hormone analog treatment. • Previous models for predicting adult height of girls with idiopathic central precocious puberty have not been proven translational to the Chinese population. What is New: • This study develops a new model for predicting the adult height of idiopathic central precocious puberty girls who underwent gonadotropin-releasing hormone analog treatment. • The internal and external validation assures a good degree of discrimination and calibration of the prediction model in this study. [ABSTRACT FROM AUTHOR]

Microencapsulated phase change materials (MEPCMs) have been widely used in many fields as thermal energy storage materials. This study reported a novel MEPCM with the functions of thermal energy storage, photothermal conversion, ultraviolet (UV) shielding, and superhydrophobicity, which was particularly suitable for intelligent textiles. The microcapsules based on an n-eicosane core and a CuO-doped polyurea shell with hierarchical structure were fabricated through a one-step interfacial polymerization. The morphology of the capsules and the hierarchical shell structure were identified through scanning and transmission electron microscopy. Thermal analysis indicated that the microcapsules had a high latent heat of 162.3 J/g and demonstrated a high thermal reliability. These microcapsules achieved a good photothermal conversion capability and can reduce UV radiation by approximately 30%. The water contact angle of the MEPCM was over 148° and showed a good superhydrophobic property. Cotton fabric coated with the prepared MEPCM was investigated. Results showed that it achieved a high phase change enthalpy of 36.8 J/g, an effective thermoregulation capability, and a large contact angle of 141.6°. [ABSTRACT FROM AUTHOR]

Neonatal hypoxic-ischemic brain damage (HIBD) is one of the leading causes of neonatal mortality and permanent neurological disability worldwide and the effective treatment strategies are not yet available. It has been demonstrated that Chitosan oligosaccharide (COS) exerts protective effect in vitro ischemic brain injury. However, no information is available on possible effects of COS on neonatal HIBD. To investigate the hypothesis of the potential neuroprotective effect of COS on the brain injury due to HIBD, 7-day-old Sprague-Dawley rats were treated with left carotid artery ligation followed by exposure to 8% oxygen (balanced with nitrogen) for 2.5 h at 37 °C. After COS treatment, the cerebral damage was measured by behavior tasks, 2,3,5-triphenyltetrazolium chloride(TTC), Hematoxyline-Eosin(HE), Nissl and Fluoro-Jade B(FJB)staining. In addition, the oxidative stress were assayed with ipsilateral hemisphere homogenates. Immunofluorescence staining were used to examine the activation of the astrocyte and microglia. Expression of inflammatory-related proteins were analyzed by western-blot analysis. In this study we found that administration of COS ameliorated early neurological reflex behavior, significantly reduce brain infarct volume and attenuated neuronal cell injury and degeneration. Furthermore, COS markedly decreased the level of MDA, lactic acid and increased SOD, GSH-Px and T-AOC. COS attenuated hypoxic-ischemic induced up-regulation of expressions of interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), meanwhile it dramatically increased the interleukin-10 (IL-10). These results suggest that COS exerts neuroprotection on hypoxic-ischemic brain damage in neonatal rats, it implies COS might be a potential therapeutic for the treatment of HIBD. [ABSTRACT FROM AUTHOR]

Sodium-dependent glucose co-transporter 2 (SGLT2) plays a pivotal role in maintaining glucose equilibrium in the human body, emerging as one of the most promising targets for the treatment of diabetes mellitus type 2. Pharmacophore models of SGLT2 inhibitors have been generated with a training set of 25 SGLT2 inhibitors using Discovery Studio V2.1. The best hypothesis (Hypo1) contains one hydrogen bond donor, five excluded volumes, one ring aromatic and three hydrophobic features, and has a correlation coefficient of 0.955, cost difference of 68.76, RMSD of 0.85. This model was validated by test set, Fischer randomization test and decoy set methods. The specificity of Hypo1 was evaluated. The pharmacophore features of Hypo1 were different from the best pharmacophore model (Hypo1) of SGLT1 inhibitors we developed. Moreover, Hypo1 could effectively distinguish selective inhibitors of SGLT2 from those of SGLT1. These results indicate that a highly predictive and specific pharmacophore model of SGLT2 inhibitors has been successfully obtained. Then Hypo1 was used as a 3D query to screen databases including NCI and Maybridge for identifying new inhibitors of SGLT2. The hit compounds were subsequently subjected to filtering by Lipinski's rule of five. And several compounds selected from the top ranked hits have been suggested for further experimental assay studies. [ABSTRACT FROM AUTHOR]

The electrochemical migration (ECM) behavior of the electrically conductive adhesives (ECAs) filled with pure Ag powder or Ag-plated Cu composite powder with varied Ag:Cu ratios was investigated under the condition of applying constant voltage and distilled water environment. ECM resistance was determined from the current-time curves. The microstructure and composition of ECM dendrite products were analyzed by SEM/EDS and XRD. It was found that the ECM resistance of Ag-plated Cu composite powder-filled ECAs was evidently higher than that of pure Ag powder-filled ECAs. The Ag:Cu ratio of composite powder in ECAs had notable influence on ECM resistance, which was enhanced with the decrease of Ag:Cu ratios. The composition of dendrites formed between cathode and anode during ECM process was not uniform for Ag-plated Cu-filled ECAs. An ECM inhibiting mechanism of Ag-plated Cu composite powder was proposed according to analysis of the electrochemical impedance spectroscopy, Tafel plot and dendrite composition. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) play a critical role in both cancer initiation and relapse as they are resistant to most cytotoxic agents and able to proliferate indefinitely. The plant alkaloid oxymatrine has many biological activities including the ability to induce cell cycle arrest and apoptosis, which makes it a potentially useful agent for targeting cancer cells. In order to determine whether it has beneficial pharmacological properties to eradicate CSCs, we analyzed the effects of oxymatrine on MCF-7 breast cancer cells. Cancer stem-like cells' (side population, SP) identification and sorting were performed. The inhibitory effect of oxymatrine was evaluated on the sorted SP and non-SP cells. The results indicated that oxymatrine caused a dose-dependent reduction in the proliferation of MCF-7 cells and a decrease in SP cells. Wnt/β-catenin signaling pathway was also examined by analyzing the expression of total β-catenin and phosphorylated β-catenin in cytoplasm, and the results showed that the growth inhibitory effects of oxymatrine treatment on MCF-7 cells may be due to the inhibition of SP and Wnt/β-catenin signaling pathway. Further work is warranted to explore whether oxymatrine may be a useful novel therapeutic drug for targeting breast CSCs. [ABSTRACT FROM AUTHOR]

Sialomucin complex (SMC, rat Muc4) is a membrane mucin implicated in the protection of epithelia and the metastasis of some tumors. It is a heterodimeric complex, containing a mucin subunit with anti-adhesive activity and a transmembrane subunit with epidermal growth factor-like domains, one of which acts as an intramembrane ligand for ErbB2. Serum, insulin and insulin-like growth factor, but not epidermal growth factor, induce the expression of sialomucin complex in mammary epithelial cells. Induction correlates with sustained, but not transient, activation of extracellular-regulated protein kinase (ERK). MEK inhibitor U0126 blocked the induction, while activated MEK-1 transfected into a rat mammary adenocarcinoma cell line induced a sustained activation of ERK and up-regulated SMC/Muc4 expression. Northern and Western blotting indicated that up-regulation occurred concomitantly at the transcript and protein levels, both of which could be blocked by U0126. These results suggest that expression of SMC/Muc4 in mammary epithelial cells is regulated by selected growth factors through an ERK-dependent pathway at the transcript level. Oncogene (2000) 19, 4354–4361 [ABSTRACT FROM AUTHOR]