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AbstractThe goal of this study was to evaluate the effects of Tenebrio molitor(TM) larvae meal on the growth performance, serum biochemical parameters and caecal metabolome of broiler chickens. A total of 600 1-d-old male Liangfenghua broilers were randomly assigned to five equal groups with 5 replicates and 24 birds in each replicate. The dietary treatments were as follows: the control group (TM0 group) was fed a basal diet, and the experimental groups were fed experimental diets in which 3% (TM3 group), 5% (TM5 group), 7% (TM7 group) and 9% (TM9 group) TM larvae meal included in the basal diet, respectively. The feeding period was 70 d. The results showed that body weight (BW) and average daily gain (ADG) significantly increased (p < 0.05) in response to dietary 3% TM larvae meal supplementation at the age of 70 d. Serum concentrations of triglyceride (TG) and serum activity of aspartate aminotransferase (AST) decreased (p < 0.05) in 3% TM larvae meal-fed broilers. UHPLC-MS/MS-based metabolomics analysis revealed that a total of 55 significantly different metabolites were obtained in the caecal contents of dietary TM larvae meal supplemented broilers. The relative contents of 28 metabolites such as trans-4-hydroxy-L-proline, thymine and retinoic acid were significantly up-regulated (FC > 1.5) and the relative contents of 27 metabolites like prostaglandin F2α, glucocorticoids and prostaglandin E2were significantly down-regulated (FC < 0.667) in the TM3 group. The main altered pathways were clustered into arachidonic acid metabolism, primary bile acid metabolism and propionic acid metabolism. In conclusion, the results indicated that supplementation of 3% TM larvae meal can improve growth performance, reduce the activity of serum AST and the content of TG, and regulation of the pathways of lipid, amino acid, and sugar metabolism in the caecum of broilers by improving nutrient digestion and absorption.

The dynamics of current controller is usually neglected for simplification when assessing microgrid transient stability. Utilizing the Takagi–Sugeno method, this letter thoroughly examines the effects of current controller on transient stability estimations and reveals that completely ignoring the dynamics of current controller can cause overestimation on transient stability. The findings highlight a significant overestimation on lower boundary of angle about 29.2% even if current controller performs fast dynamics with bandwidth more than 28 times the fundamental frequency. Recognizing the impracticality of including current controller dynamics in microgrids with multiple converters, this letter proposes a stability-enhanced method through phase compensation in the current controller, which can improve the accuracy of transient stability assessments while still omitting current controller dynamics. In addition, a guideline for parameter design of phase compensation is provided. Theoretical findings are verified by hardware-in-loop experimental results based on OPAL-RT platform.

Near-infrared fluorescence (NIRF) probes greatly facilitate in vivo imaging of various biologically important species. However, there are several significant limitations such as consuming washing steps, photobleaching, and low signal intensity. Herein, we synthesized fluorescent copper nanosheets templated with DNA scaffolds (DNS/CuNSs). We employ them and Cy5.5 of the fluorescence resonance energy transfer (FRET) system, which have a larger Stokes shift (∼12-fold) than the traditional NIRF dye Cy5.5. Based on their excellent fluorescence properties, we employ DNS/CuNSs-Cy5.5 for fluorescence probes in cancer cell imaging. Compared with the free Cy5.5 fluorescence probe, the novel fluorescence imaging probe implements wash-free imaging and exhibits enhanced anti-photobleaching ability (∼5.5-fold). Moreover, the FRET system constructed by DNS/CuNSs has a higher signal amplification ability (∼4.17-fold), which is more similar to that of Cu nanoclusters prepared with DNA nanomonomers as a template. This work provides a new idea for cancer cell MCF-7 imaging and is expected to promote the development of cancer cell fluorescence imaging.

ABSTRACTCurrently, abnormally elevated rail potential exists in the DC traction power system, which greatly threatens the safe operation of the line. In order to realize the reflux safety, timetable optimization of multitrain based on improved Seeker Optimization Algorithm (SOA) is proposed to suppress the rail potential of the system. Firstly, the simulation model of the system is built and the calculation process of rail potential is proposed. Secondly, an optimization model based on maximum rail potential is formulated, where the dwell time is the decision variable and is adjusted to change the regenerative power distribution of the system. Finally, the improved SOA is used to handle the optimization model. Compared with the maximum rail potential before optimization, the simulation results demonstrate that the maximum rail potential is reduced by 55.5% with the proposed method, which greatly improves the reflux safety of the multi-train subway system.

Radiotherapy (RT) is one of the most extensive and effective approaches available for clinical tumor treatment. However, tumor microenvironments including hypoxia and histone deacetylase (HDAC) overexpression could induce radiation resistance, leading to tumor recurrence. Herein, nanoparticles (CAT-SAHA@PLGA) encapsulating catalase and HDAC inhibitor SAHA exhibited protected catalytic activity of catalase and prolonged the pharmacokinetic exposure of the HDAC inhibitor. Overall, the established CAT-SAHA@PLGA nanoparticles could overcome radiation resistance by synergistically increasing tumor oxygenation and inhibiting HDAC activity.

Nanozymes have been developed to overcome the inherent limitations of natural enzymes, such as their low stability and high cost. However, their efficacy has been hindered by their relatively low specificity and activity. Here, we demonstrate the self-assembly of individual copper nanoclusters (CuNCs) via a simple yet fast (10 min) DNA nanosheet (DNS)-templated method, enhancing the peroxidase-like activity and specificity of CuNCs. Furthermore, we demonstrate the successful assembly of CuNCs on different DNA nanostructures by atomic force microscopy (AFM), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). The resulting micron-scale ultrathin DNA nanosheet-templated CuNCs (DNS@CuNCs) exhibit exceptional catalytic activity, with a specific activity reaching 1.79 × 103U mg–1. Investigation into the catalytic process reveals that the enhanced activity and specificity arise from disparities in active intermediate content before and after CuNCs assembly. Significantly, the DNS@CuNCs-based biosensor demonstrates remarkable anti-interference capabilities, enabling the detection of H2O2in undiluted human serum for the first time with a detection limit of 0.99 μM.

Doxorubicin (DOX) liposome is a widely used nano-medicine for colorectal cancer treatment. However, doxorubicin therapy increases the level of reactive oxygen species (ROS) in tumor cells, such as hydrogen peroxide (H2O2), which can stabilize hypoxia-inducible-factor-1α (HIF-1α). In a tumor hypoxic microenvironment, HIF-1 can up-regulate tumor-resistance related proteins, including P-glycoprotein (P-gp), glucose transporter 1 (GLUT-1), and matrix metalloproteinase 9 (MMP-9), leading to tumor tolerance to chemotherapy. The functional inhibition of HIF-1 can overcome this resistance and enhance the efficacy of tumor therapy. Here, we encapsulated one of the most effective HIF-1 inhibitors, acriflavine (ACF), and DOX in liposomes (DOX-ACF@Lipo) to construct bifunctional liposomes. ACF and DOX, released from DOX-ACF@Lipo, could effectively suppress the function of HIF-1 and the process of DNA replication, respectively. Consequently, the bifunctional liposome has great potential to be applied in clinics to overcome chemotherapy resistance induced by hypoxia.

Hypoxia, and hypoxia inducible factor-1 (HIF-1), can induce tumor resistance to radiation therapy. To overcome hypoxia-induced radiation resistance, recent studies have described nanosystems to improve tumor oxygenation for immobilizing DNA damage and simultaneously initiate oxygen-dependent HIF-1α degradation. However, HIF-1α degradation is incomplete during tumor oxygenation treatment alone. Therefore, tumor oxygenation combined with residual HIF-1 functional inhibition is crucial to optimizing therapeutic outcomes of radiotherapy. Here, a reactive oxygen species (ROS) responsive nanoplatform is reported to successfully add up tumor oxygenation and HIF-1 functional inhibition. This ROS responsive nanoplatform, based on manganese dioxide (MnO2) nanoparticles, delivers the HIF-1 inhibitor acriflavine and other hydrophilic cationic drugs to tumor tissues. After reacting with overexpressed hydrogen peroxide (H2O2) within tumor tissues, Mn2+and oxygen molecules are released for magnetic resonance imaging and tumor oxygenation, respectively. Cooperating with the HIF-1 functional inhibition, the expression of tumor invasion-related signaling molecules (VEGF, MMP-9) is obviously decreased to reduce the risk of metastasis. Furthermore, the nanoplatform could relieve T-cell exhaustion viadownregulation of PD-L1, whose effects are similar to the checkpoint inhibitor PD-L1 antibody, and subsequently activates tumor-specific immune responses against abscopal tumors. These therapeutic benefits including increased X-ray-induced damage, downregulated resistance, and T-cell exhaustion related proteins expression achieved synergistically the optimal inhibition of tumor growth. Overall, this designed ROS responsive nanoplatform is of great potential in the sensitization of radiation for combating primary and metastatic tumors.

Abraxane® (Abx), an FDA approved albumin-bound paclitaxel nano-formulation, is one of the most common chemical drugs for the treatment of metastatic triple-negative breast cancer (mTNBC). However, acquired resistance and metastasis are critical factors that limit the treatment of mTNBC by Abx. In particular, both the tumor hypoxic microenvironment and the increase in hydrogen peroxide (H2O2) levels viapaclitaxel stimulation primarily mediate the resistance to chemotherapy, where multiple drug resistance proteins such as P-gp and tumor invasion-related cytokines such as VEGF are continuously activated to pump out chemical drugs and aggravate tumor metastasis, respectively. Therefore, it is of great importance to combine tumor oxygenation with commercial chemical drugs for overcoming the acquired resistance and metastasis. In this study, a facile method was developed to deposit manganese dioxide (MnO2) onto the surface of Abraxane® (Abx) to form MnO2-modified Abx (M-Abx). The modification process did not change the critical characteristics of the parent Abx, which might have great potential for application in clinics for the treatment of mTNBC. Tumor oxygenation mediated by M-Abx specifically occurs within the H2O2-overexpressed tumor microenvironment, and significantly downregulates the content of tumor progression-related proteins, such as HIF-1α, P-gp, and VEGF. Ultimately, M-Abx treatment results in about a 2-fold increase in inhibition efficiency of tumor growth in both primary and metastatic tumors compared with traditional Abx therapy. Therefore, oxygen-rich chemotherapy was realized to efficiently sensitize paclitaxel, relieve acquired resistance and inhibit tumor metastasis.