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Low accumulation of anticancer drugs in tumors and serious systemic toxicity remain the main challenges to the clinical efficiency of pharmaceuticals. Pulmonary delivery of nanoscale-based drug delivery systems offered a strategy to increase antitumor activity with minimal adverse exposure. Herein, we report an osimertinib-loaded perfluoro-15-crown-5-ether (AZD9291-PFCE) nanoemulsion, through intratracheal and intravenous delivery, synergizes with

Daoshuang Li,1,2,* Jie Yang,1,2,* Zuoyu Xu,1,2 Yingbo Li,1,2 Yige Sun,1,2 Yuchen Wang,1,2 Hongyan Zou,1,2 Kai Wang,1,2 Lili Yang,1,2 Lina Wu,1,2 Xilin Sun1,2 1Department of Nuclear Medicine, the Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 2NHC Key Laboratory of Molecular Probe and Targeted Diagnosis and Therapy, Molecular Imaging Research Center (MIRC) of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xilin Sun; Lina Wu, Department of Nuclear Medicine, the Fourth Hospital of Harbin Medical University, 766 Xiangan N Street, Songbei District, Harbin, Heilongjiang, 150028, People’s Republic of China, Tel +86-451-88118600, Fax +86-451-82576509, Email sunxl@ems.hrbmu.edu.cn; LinaWu@hrbmu.edu.cnPurpose: Precisely detecting colorectal liver metastases (CLMs), the leading cause of colorectal cancer-associated mortality, is extremely important. 1H MRI with high soft tissue resolution plays a key role in the diagnosing liver lesions; however, precise detecting CLMs by 1H MRI is a great challenge due to the limited sensitivity. Even though contrast agents may improve the sensitivity, due to their short half-life, repeated injections are required to monitor the changes of CLMs. Herein, we synthesized c-Met-targeting peptide-functionalized perfluoro-15-crown-5-ether nanoparticles (AH111972-PFCE NPs), for highly sensitive and early diagnosis of small CLMs.Methods: The size, morphology and optimal properties of the AH111972-PFCE NPs were characterized. c-Met specificity of the AH111972-PFCE NPs was validated by in vitro experiment and in vivo 19F MRI study in the subcutaneous tumor murine model. The molecular imaging practicability and long tumor retention of the AH111972-PFCE NPs were evaluated in the liver metastases mouse model. The biocompatibility of the AH111972-PFCE NPs was assessed by toxicity study.Results: AH111972-PFCE NPs with regular shape have particle size of 89.3 ± 17.8 nm. The AH111972-PFCE NPs exhibit high specificity, strong c-Met-targeting ability, and precise detection capability of CLMs, especially small or ill-defined fused metastases in 1H MRI. Moreover, AH111972-PFCE NPs could be ultralong retained in metastatic liver tumors for at least 7 days, which is conductive to the implementation of continuous therapeutic efficacy monitoring. The NPs with minimal side effects and good biocompatibility are cleared mainly via the spleen and liver.Conclusion: The c-Met targeting and ultralong tumor retention of AH111972-PFCE NPs will contribute to increasing therapeutic agent accumulation in metastatic sites, laying a foundation for CLMs diagnosis and further c-Met targeted treatment integration. This work provides a promising nanoplatform for the future clinical application to patients with CLMs.Keywords: c-Met-targeted, perfluorocarbon, 19F MRI, colorectal liver metastases, precise detection

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder characterized by atypical patterns of social interaction and communication as well as restrictive and repetitive behaviors. Additionally, ASD often presents with sleep disturbances. Delta (δ) catenin protein 2 (CTNND2) encodes δ-catenin protein, a neuron-specific catenin implicated in many complex neuropsychiatric diseases. Our previous study had exhibited deletion of Ctnnd2 in mice lead to autism-like behaviors. However, to our knowledge, no studies have investigated the effects of Ctnnd2 deletion in sleep of mice. In this study, we investigated whether knockout (KO) of exon 2 of the Ctnnd2 gene could induce sleep-wake disorders in mice and identify the effects of oral melatonin (MT) supplementation on KO mice. Our results demonstrated that KO mice exhibited ASD-like behaviors and sleep-wake disorders and they were attenuated, in part, by MT supplementation. Moreover, we further proved the correlation between autism-like behaviors and sleep-wake disorders in KO mice. MT may improve ASD-like behaviors by attenuating sleep-wake dysfunction. Overall, our current study was the first to identify that knockdown of Ctnnd2 gene could induce sleep-wake disorders in mice and had a correlation between sleep and phenotypes of ASD in Ctnnd2 KO mice. Our findings suggest that treatment of sleep-wake disturbances benefits on Ctnnd2 gene-deletion caused autism-like behaviors.

Organic-inorganic hybrid perovskite (OIHP) polycrystalline films are the key light-absorbing layers of laminated-structure OIHP-based devices that have attracted increasing attention in photoelectronics and flexible electronics. Internal stresses induced by the mismatched responses of laminated layers to long-term and cyclic multiphysical fields generate time-dependent mechanical deformation in OIHP polycrystalline films, which makes the mechanical constitution relation of great significance. However, few studies focus on either the mechanical properties and behaviors of OIHP polycrystalline films or the underlying mechanism coupled with the grain structure and ion diffusion. Here, we uncovered the heterogeneous viscoelasticity of MAPbBr

Increasing the electrochemical stability window and working temperature range of supercapacitor aqueous electrolyte is the major task in order to advance aqueous electrolyte-based supercapacitors. Here, a supramolecular induced new electrolyte of lithium bis(trifluoromethanesulfonyl) imide (LiTFSI) in dimethyl sulfoxide (DMSO) and water co-solvent system is proposed. Adjusting the coordination structure among LiTFSI, DMSO, and water in the electrolyte via supramolecular interactions results in its high ionic conductivity, low viscosity, wide electrochemical stability window, and large working temperature range. The new electrolyte-based supercapacitors can work in 2.40 V working potential and 130 °C working-temperature range from −40 to 90 °C. The devices exhibit good electrochemical performances, especially the energy density over 21 Wh kg−1, which is much higher than that with traditional aqueous electrolytes (

Inefficient tumor accumulation and penetration remain as the main challenges to therapy efficacy of lung cancer. Local delivery of smart nanoclusters can increase drug penetration and provide superior antitumor effects than systemic routes. Here, we report self-assembled pH-sensitive superparamagnetic iron oxide nanoclusters (SPIONCs) that enhance

Over application of nitrogen (N) fertilizers to crops ultimately causes N pollution in the ecosphere. Studying the response of plant growth and N uptake to low-N stress may aid in elucidating the mechanism of low N tolerance in plants and developing crop cultivars with high nitrogen use efficiency (NUE). In this study, a high-NUE mutant line A9-29 and the wild-type barley cultivar Hua30 were subjected to hydroponic culture with high and low N supply, and the dry weight, N accumulation, root morphology, and expression levels of the potential genes involved in nitrate uptake and assimilation were measured at seedling stage. The results showed that under low-N conditions, A9-29 had a higher dry weight, N content, N influx rate and larger root uptake area than did Hua30. Under long-term low-N stress, compared with Hua30, A9-29 demonstrated higher expression of the HvNRT2/3 genes, especially HvNRT2.1, HvNRT2.5, and HvNRT3.3. Similarly, the expression levels of N assimilation genes including HvNIA1, HvNIR1, HvGS1_1, HvGS1_3, and HvGLU2 increased significantly in A9-29. Taken together, our results suggested that the larger root area and the upregulation of nitrate transporter and assimilation genes may contribute to stronger N uptake capacity for plant growth and N accumulation in responding to long-term low-N stress. These findings may aid in understanding the mechanism of low N tolerance and developing barley cultivars with high-NUE.

Powdery mildew (Pm), caused by Blumeria graminis f.sp. tritici (Bgt), is one of the most important wheat diseases. Heavy-metal-associated isoprenylated plant protein (HIPP1) has been proved playing important roles in response to biotic and a biotic stress. In present study, we proved HIPP1-V from Haynalidia villosa is a positive regulator in Pm resistance. HIPP1-V was rapidly induced by Bgt. Transiently or stably heterologous overexpressing HIPP1-V in wheat suppressed the haustorium formation and enhanced Pm resistance. HIPP1-V isoprenylation was critical for plasma membrane (PM) localization, interaction with E3-ligase CMPG1-V and function in Pm resistance. Bgt infection recruited the isoprenylated HIPP1-V and CMPG1s on PM; blocking the HIPP1 isoprenylation reduced such recruitment and compromised the resistance of OE-CMPG1-V and OE-HIPP1-V. Overexpressing HIPP1-VC

Dasypyrum villosum L. is one of the most valuable gene resources in wheat improvement, especially for disease resistance. The mining of favorable genes from D. villosum is frustrated by the lack of genome sequence. Here, by generating a doubled haploid line 91C43

Intermetallic catalysts are of immense interest, but how heterometals diffuse and related interface structure remain unclear when there exists a strong metal-support interaction. Here, we developed a kinetic diffusion–controlled method and synthesized intermetallic Pt 2 Mo nanocrystals with twin boundaries on mesoporous carbon (Pt 2 Mo/C). The formation of small-sized twinned intermetallic nanocrystals is associated with the strong Mo-C interaction–induced slow Mo diffusion and the heterogeneity of alloying, which is revealed by an in situ aberration-corrected transmission electron microscope (TEM) at high temperature. The twinned Pt 2 Mo/C constitutes a promising CO-resistant catalyst for highly selective hydrogenation of nitroarenes. Theoretical calculations and environmental TEM suggest that the weakened CO adsorption over Pt sites of Pt 2 Mo twin boundaries and their local region endows them with high CO resistance, selectivity, and reusability. The present strategy paves the way for tailoring the interface structure of high–melting point Mo/W-based intermetallic nanocrystals that proved to be important for the industrially viable reactions.

A novel organomediated cleavage of benzoyl group using ethane-1,2-diamine and acetic acid under neutral condition enables an efficient synthesis of 1-(6-nitropyridin-2-yl)thiourea, which previously has been challenging to prepare by conventional methods. The successful synthesis of 1-(6-nitropyridin-2-yl)thiourea as a synthon permits development of a variety of (18)F labeled heterocycles as PET imaging ligands such as N-(pyridin-2-yl)thiazol-2-amine derivatives. The utility of this synthon is demonstrated with the synthesis of a (18)F-labeled PET tracer for studying prion disease. In vitro autoradiography using this PET tracer on sagittal rat brain slices showed highest accumulation of radioactivity in the hippocampus, cortex, and striatum, in accordance with reported immunostaining of PrP(c) in rat brain.

Developing unique single atoms as active sites is vitally important to boosting the efficiency of photocatalytic CO2 reduction, but directly atomizing metal particles and simultaneously adjusting the configuration of individual atoms remain challenging. Herein, we demonstrate a facile strategy at a relatively low temperature (500 °C) to access the in situ metal atomization and coordination adjustment via the thermo-driven gaseous acid. Using this strategy, the pyrolytic gaseous acid (HCl) from NH4Cl could downsize the large metal particles into corresponding ions, which subsequently anchored onto the surface defects of a nitrogen-rich carbon (NC) matrix. Additionally, the low-temperature treatment-induced C═O motifs within the interlayer of NC could bond with the discrete Fe sites in a perpendicular direction and finally create stabilized Fe-N4O species with high valence status (Fe3+) on the shallow surface of the NC matrix. It was found that the Fe-N4O species can achieve a highly efficient CO2 conversion when accepting energetic electrons from both homogeneous and heterogeneous photocatalysts. The optimized sample achieves a maximum turnover number (TON) of 1494 within 1 h in CO generation with a high selectivity of 86.7% as well as excellent stability. Experimental and theoretical results unravel that high valence Fe sites in Fe-N4O species can promote the adsorption of CO2 and lower the formation barrier of key intermediate COOH* compared with the traditional Fe-N4 moiety with lower chemical valence. Our discovery provides new points of view in the construction of more efficient single-atom cocatalysts by considering the optimization of the atomic configuration for high-performance CO2 photoreduction.