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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

The performance of lithium-ion batteries is determined by the architecture and properties of electrodes formed during manufacturing, particularly in the drying process when solvent is removed and the electrode structure is formed. Temperature is one of the most dominant parameters that influences the process, and therefore a comparison of temperature effects on both NMC622-based cathodes (PVDF-based binder) and graphite-based anodes (water-based binder) dried at RT, 60, 80, 100 and 120 °C has been undertaken. X-ray computed tomography showed that NMC622 particles concentrated at the surface of the cathode coating except when dried at 60 °C. However, anodes showed similar graphite distributions at all temperatures. The discharge capacities for the cathodes dried at 60, 80, 100 and 120 °C displayed the following trend: 60 °C < 80 °C < 100 °C < 120 °C as C-rate was increased which was consistent with the trends found in adhesion testing between 60 and 120 °C. Focused-ion beam scanning electrode microscopy and energy-dispersive X-ray spectroscopy suggested that the F-rich binder distribution was largely insensitive to temperature for cathodes. In contrast, conductivity enhancing fine carbon agglomerated on the upper surface of the active NMC particles in the cathode as temperature increased. The cathode dried at RT had the highest adhesion force of 0.015 N mm−1 and the best electrochemical rate performance. Conversely, drying temperature had no significant effect on the electrochemical performance of the anode, which was consistent with only a relatively small change in the adhesion, related to the use of lower adhesion water-based binders.

Phototherapy, such as photodynamic therapy (PDT) and photothermal therapy (PTT), possesses unique characteristics of non-invasiveness and minimal side effects in cancer treatment, compared with conventional therapies. However, the ubiquitous tumor hypoxia microenvironments could severely reduce the efficacy of oxygen-consuming phototherapies. Perfluorocarbon (PFC) nanomaterials have shown great practical value in carrying and transporting oxygen, which makes them promising agents to overcome tumor hypoxia and extend reactive oxygen species (ROS) lifetime to improve the efficacy of phototherapy. In this review, we summarize the latest advances in PFC-based PDT and PTT, and combined multimodal imaging technologies in various cancer types, aiming to facilitate their application-oriented clinical translation in the future.

In this work, we synthesized micro-mesoporous graphene1−x(MoS2)x with different compositional ratios via co-reduction of graphite oxide and exfoliated MoS2 platelets. We systematically studied the performance of the micro-mesoporous graphene1−x(MoS2)x as anodes in lithium-ion batteries and sodium-ion batteries. The results show that the specific surface areas of the composites decrease with introducing MoS2. The irreversible capacitance, which is related to the formation of solid electrolyte interphases, also decreases. Besides specific surface area, we found that micropores can benefit the lithiation and sodiation. We demonstrated that a specific charge capacity of 1319.02 mA h g−1 can be achieved at the 50th cycle for the graphene½(MoS2)½ anode in lithium-ion batteries. Possible relationships between such a high specific capacity and the micro-mesoporous structure of the graphene1−x(MoS2)x anode are discussed. This work may shed light on a general strategy for the structural design of electrode materials in lithium-ion batteries and sodium-ion batteries.

Drug side effects have become an important indicator for evaluating the safety of drugs. There are two main factors in the frequent occurrence of drug safety problems; on the one hand, the clinical understanding of drug side effects is insufficient, leading to frequent adverse drug reactions, while on the other hand, due to the long-term period and complexity of clinical trials, side effects of approved drugs on the market cannot be reported in a timely manner. Therefore, many researchers have focused on developing methods to identify drug side effects. In this review, we summarize the methods of identifying drug side effects and common databases in this field. We classified methods of identifying side effects into four categories: biological experimental, machine learning, text mining and network methods. We point out the key points of each kind of method. In addition, we also explain the advantages and disadvantages of each method. Finally, we propose future research directions.

Powder materials are used in all corners of materials science, from additive manufacturing to energy storage. Scanning electron microscopy (SEM) has developed to meet morphological, microstructural and bulk chemical powder characterization requirements. These include nanoscale elemental analysis and high-throughput morphological assays. However, spatially localized powder surface chemical information with similar resolution to secondary electron (SE) imaging is not currently available in the SEM. Recently, energy filtered (EF-) SEM has been used for surface chemical characterization by secondary electron hyperspectral imaging (SEHI). This review provides a background to existing powder characterization capabilities in the low voltage SEM provided by SE imaging, EDX analysis and BSE imaging and sets out how these capabilities could be extended for surface chemical analysis by applying SEHI to powders, with particular emphasis on air and beam sensitive powder surfaces. Information accessible by SEHI, its advantages and limitations, is set into the context of other chemical characterization methods that are commonly used for assessing powder surface chemistry such as by Auger electron spectroscopy (AES) and X-ray photoelectron spectroscopy (XPS). The applicability of existing powder preparation methods for SEM to SEHI is also reviewed. An alternative preparation method is presented alongside first examples of SEHI characterization of powder surfaces. The commercial powder materials used as examples were carbon-fiber/polyamide composite powder feedstock (CarbonMide®) used in additive manufacturing and powders consisting of lithium nickel cobalt oxide (NMC). SEHI is shown to differentiate bonding present at carbonaceous material surfaces and extract information about the work function of metal oxide surfaces. The surface sensitivity of SEHI is indicated by comparison of pristine powders to those with surface material added in preparation. A minimum spatial localization of chemical information of 55 nm was achieved in differentiating regions of NMC surface chemistry by distinct SE spectra.

A novel method for producing graphene via enhanced shear exfoliation in a high-pressure fluid has been developed. In the process of exfoliation, graphite flakes, dispersed in a solution of N-methyl-2-pyrrolidone (NMP), were pushed through the exfoliation tube by a high-pressure pump, which produces high shear stresses on the graphite flakes due to the turbulent flow, causing the peeling-off of graphene sheets from the graphite flake. Atomic force microscopy (AFM) and transmission electron microscopy (TEM) images show that produced graphene sheets have thicknesses ranging from monolayer to about 12 layers. The results of X-ray photoelectron spectroscopy (XPS) and Raman and infrared (IR) spectroscopy analyses reveal that neither basal-plane defects nor oxides were noticeably introduced to graphene sheets in the process. The graphite solution can be continuously treated in a circular loop. At a pressure of 100 MPa and after 2 h of treatment, exfoliated graphene was obtained with a yield of about 15 ± 0.3%. T...

Carbon nanotubes (CNTs) are an effective spacer to prevent the re-stacking of graphene layers. However, the aggregation of CNTs always reduces the specific surface area of resulting CNT/graphene composites. Meanwhile, different pores always have different contributions to the specific capacitance. In this study, CNT/graphene composites with different porous structures are synthesized by co-reduction of oxidized CNTs and graphene oxide with different mixing ratios. With an optimized CNT content of 20%, the CNT/graphene composite shows 206 F g−1 in 1-ethyl-3-methylimidazolium tetrafluoroborate electrolyte. It is found that pores larger than twice the size of electrolyte ions can make greater contributions to the specific capacitance.

Unequal electrode capacitance in a symmetric supercapacitor results in an unequal voltage distribution on the two electrodes and the supercapacitor usually cannot utilize the full electrochemical window of electrolyte. In this study, the voltage distribution on the two electrodes of graphene supercapacitor is optimized by an adjustment of electrode mass ratio from 1 to 1.5 and an enlarged energy density of 118 Wh kg−1 is achieved at operating voltage 4.7 V using an ionic liquid electrolyte 1-methyl-1-propylpiperidinium bis (trifluoromethyl sulfonyl) imide (MPPp-TFSI).

Hydrazine-reduced graphite oxide and graphene oxide were synthesized to compare their performances as anode materials in lithium-ion batteries and sodium-ion batteries. Reduced graphite oxide inherits the layer structure of graphite, with an average spacing between neighboring layers (d-spacing) of 0.374 nm; this exceeds the d-spacing of graphite (0.335 nm). The larger d-spacing provides wider channels for transporting lithium ions and sodium ions in the material. We showed that reduced graphite oxide as an anode in lithium-ion batteries can reach a specific capacity of 917 mA h g−1, which is about three times of 372 mA h g−1, the value expected for the LiC6 structures on the electrode. This increase is consistent with the wider d-spacing, which enhances lithium intercalation and de-intercalation on the electrodes. The electrochemical performance of the lithium-ion batteries and sodium-ion batteries with reduced graphite oxide anodes show a noticeable improvement compared to those with reduced graphene oxide anodes. This improvement indicates that reduced graphite oxide, with larger interlayer spacing, has fewer defects and is thus more stable. In summary, we found that reduced graphite oxide may be a more favorable form of graphene for the fabrication of electrodes for lithium-ion and sodium-ion batteries and other energy storage devices.

We have designed and synthesized a unique structured graphene/SnO2 composite, where SnO2 nanoparticles are inserted in between interconnected graphene sheets which form hollow spherical multilayers. The hollow spherical multilayered structure provides much flexibility to accommodate the configuration and volume changes of SnO2 in the material. When it is used as an anode material for lithium-ion batteries, such a novel nanostructure can not only provide a stable conductive matrix and suppress the mechanical stress, but also eliminate the need of any binders for constructing electrodes. Electrochemical tests show that the unique graphene/SnO2 composite electrode as designed could exhibit a large reversible capacity over 1000 mA h g−1 and long cycling life with 88% retention after 100 cycles. These results indicate the great potential of the composite for being used as a high performance anode material for lithium-ion batteries.

The dramatically increased demand for electric devices such as electric vehicles and consumer electronics prompted us to explore new ideas in fabricating novel energy storage devices. In this work, we designed, constructed, and studied an asymmetric hybrid lithium-ion capacitor (LIC) by combining an electric double-layer capacitor cathode and a lithium-ion battery anode. Both electrodes were made of a single-wall carbon nanotube and graphene (SG) composite to reduce restacking of the graphene nanosheets, to improve the energy storage capacity, and to improve the electrical conductivity of the electrodes. One of the electrodes was pre-lithiated electrochemically. After pre-lithiation, the lithiated-SG (Li-SG) electrode showed excellent capacity in lithium intercalation and de-intercalation and was used as the anode of the LIC device. The advantage of the hybrid LIC with asymmetric graphene electrodes is that it maximizes the operable voltage between the two electrodes, thus increasing the energy density of the device. The hybrid LIC fabricated in this work exhibited an energy density of 222 W h kg−1 at a power density of 410 W kg−1.

The robotic job-shop scheduling problem (RJSP) has become increasingly important due to the wide application of robots for material delivery in modern logistics and supply chain systems. With the common assumptions of negligible material transportation procedures and infinite machine buffers, the traditional job-shop scheduling problem (JSP) models can lead to system failures due to the potential deadlock for a robot-driven production line. In this study, we propose two novel robotic job-shop scheduling models with deadlock and robot movement considerations (RJSPDT). The proposed novel models simultaneously consider the scheduling of job operations and the movement of the robot, with the objective of minimizing makespan. In order to avoid deadlock, the machine blocking strategy is applied and a set of tight deadlock-avoidance constraints is proposed. Two modelling approaches are applied: the traditional position-based approach and the novel network-based approach which is inspired by aviation scheduling studies. Through numerical examples, it is illustrated that our proposed models can completely avoid transportation conflicts by considering deadlock and robot movement. Besides, through computational experiments, the network-based RJSPDT shows higher solution efficiency owing to the smaller model size than the position-based RJSPDT (e.g., reducing the computational time by 96% for small-scale problems). Moreover, we explore the impacts of job settings (e.g., number of jobs, number of operations in a job) and job entrance strategies (i.e., fixed entrance and flexible entrance) on model performances. Results show that the number of jobs imposes greater impacts than the number of operations in a job, while the fixed entrance strategy can reduce the average computational time by 60% with little impact on the makespan.

The airline crew scheduling problem has become a crucial but challenging task for commercial airlines for decades. Airlines are operating with two types of air crew: cockpit crew and cabin crew. Due to the unique operating characteristics, the scheduling problems for these two crew types are very different. Besides, according to the planning stage, the airline crew scheduling problem can be classified as tactical planning problems (traditional scheduling and robust scheduling, weeks or months before the actual operations) and operational planning problems (recovery, after disruptions have occurred during the operational stage). Realizing the significance of the airline crew scheduling problems and a lack of review on the modelling and algorithmic advancements in terms of each crew type and planning stage, we develop this paper to review the related literature from four aspects: the scheduling for cabin crew, the scheduling for both cabin crew and cockpit crew, the robust scheduling for cockpit crew, and the recovery for cockpit crew. For each stream, we examine a number of prior representative studies to review the advancements in model development and solution algorithm construction to generate insights. Finally, we conclude the review by proposing a future research agenda for the airline crew scheduling problem.

The graphene material prepared by the chemical reduction method usually has oxygenic functional groups in it and such functional groups often result in interactions between the graphene electrode and the electrolyte in supercapacitors. We have examined the existential form of interactions between graphene as the electrode and three kinds of ionic liquid, 1-ethyl-3-methylimidazolium bis (trifluoromethylsulfonyl) imide (EMI-TFSI), 1-ethyl-3-methylimidazolium tetrafluoroborate (EMI-BF 4 ), and 1-methyl-1-propylpiperidinium bis (trifluoromethyl sulfonyl) imide (MPPp-TFSI), as the electrolyte of a supercapacitor. Mass spectroscopy (MS) and Fourier transform infrared spectroscopy (FT-IR) analyses confirmed that the residual hydroxyl groups in graphene were transferred to EMI + and TFSI − lost oxygen atoms to graphene, while little reaction took place in BF 4 − or MPPp + , during the process of charging. The chemical reactions are suggested to contribute to the device capacitance while it is also one of the reasons for the decreased electrochemical stability window. In this study the highest energy density achieved using the graphene electrode is 169 Wh kg −1 in MPPp-TFSI electrolyte charged to 4.4 V.

We have designed and synthesized a unique structured graphene/SnO

Microfibrous-structured 1Au-xAg/Al-fiber (x = 0.2, 0.4 and 0.6 wt%) catalysts prepared by galvanic stepwise deposition of Au and Ag onto Al-fiber network have been tested for the oxidative coupling of methanol to methyl formate. Among these catalysts, 1Au-0.2Ag/Al-fiber provided high activity, selectivity and good stability, by nature, due to the well-dispersed Ag metal phase to facilitate the availability of reactive oxygen species. The increase of Ag loading led to the screening of surface Au which favours the adsorption of methanol, thus deteriorating methanol conversion.

Mechanical loading of the skeleton, as achieved during daily movement and exercise, preserves bone mass and stimulates bone formation, whereas skeletal unloading from prolonged immobilization leads to bone loss. A functional interplay between the insulin-like growth factor 1 receptor (IGF1R), a major player in skeletal development, and integrins, mechanosensors, is thought to regulate the anabolic response of osteogenic cells to mechanical load. The mechanistic basis for this cross-talk is unclear. Here we report that integrin signaling regulates activation of IGF1R and downstream targets in response to both IGF1 and a mechanical stimulus. In addition, integrins potentiate responsiveness of IGF1R to IGF1 and mechanical forces. We demonstrate that integrin-associated kinases, Rous sarcoma oncogene (SRC) and focal adhesion kinase (FAK), display distinct actions on IGF1 signaling; FAK regulates IGF1R activation and its downstream effectors, AKT and ERK, whereas SRC controls signaling downstream of IGF1R. These findings linked to our observation that IGF1 assembles the formation of a heterocomplex between IGF1R and integrin β3 subunit indicate that the regulation of IGF1 signaling by integrins proceeds by direct receptor-receptor interaction as a possible means to translate biomechanical forces into osteoanabolic signals.

We present a one-step synthesis process for ultrathin non-crystalline MnO2 nanosheets. Their thickness is about 2 nm and the width varies from 5 to 20 nm. They induce a higher capacitance than zero-dimensional spheres or one-dimensional rods. When heat treated at elevated temperature MnO2 nanosheets partly grow into crystalline Mn2O3 rods.