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Carbon fiber reinforced plastic (CFRP)/Ti6Al4V stacks are widely used in the aircraft industry, and drilling these stacks is essential during the assembly process. To solve the problem of high drilling temperatures in CFRP/Ti6Al4V stacks, which lead to poor tool life and hole quality, the effects of three cooling strategies compose minimum quantity lubrication (MQL), water-based coolant, and internal air cooling, were investigated in this study. Tensile/compressive strength and fatigue-life tests were conducted to evaluate the applicability of the cooling medium before drilling. Then, low-frequency vibration-assisted drilling of CFRP/Ti6Al4V stacks was performed to investigate and analyze their machinability under the three cooling strategies by analyzing the drilling temperature, thrust force, tool wear, chip removal capacity, and hole quality. The results show that the selected cooling media, including Rhenus XT46 and Accu-Lube LB2000, are applicable in CFRP drilling, whereas the adopted media, compared with water, have little influence on the tensile/compressive strength and fatigue life of the CFRP. Compared with internal air cooling and MQL, water-based coolant can more effectively improve the machinability of CFRP/Ti6Al4V stacks, decreasing the CFRP drilling temperature by 41.6 % and 40.1 %, respectively, while the reductions in the Ti6Al4V drilling temperature are 76.7 % and 57.4 %, respectively. Meanwhile, under water-based coolants, the thrust force reductions in the drilling of CFRP are 13.1 % and 11.7 %, whereas those in the drilling of Ti6Al4V are 11.0 % and 7.8 %, respectively, compared with the internal air and MQL. In addition, under the water-based coolant condition, the tool wear rate is the slowest and the hole quality is the best among the three cooling strategies, whereas a high injection pressure further decreases the VBmax value. Furthermore, under the water-based coolant conditions, the Ti6Al4V exit burr height and CFRP exit delamination are the lowest. These findings provide useful insights into improving the machinability of CFRP/Ti6Al4V stacks in the aerospace industry, particularly for drilling that requires high-quality holes and a long tool life.

Cancer cells could be eradicated by promoting generation of excessive intracellular reactive oxygen species (ROS) via emerging nanomedicines. However, tumor heterogeneity and poor penetration of nanomedicines often lead to diverse levels of ROS production in the tumor site, and ROS at a low level promote tumor cell growth, thus diminishing the therapeutic effect of these nanomedicines. Herein, we construct an amphiphilic and block polymer-dendron conjugate-derived nanomedicine (Lap@pOEGMA-b-p(GFLG-Dendron-Ppa), GFLG-DP/Lap NPs) that incorporates a photosensitizer, Pyropheophorbide a (Ppa), for ROS therapy and Lapatinib (Lap) for molecular targeted therapy. Lap, an epidermal growth factor receptor (EGFR) inhibitor that plays a role in inhibiting cell growth and proliferation, is hypothesized to synergize with ROS therapy for effectively killing cancer cells. Our results suggest that the enzyme-sensitive polymeric conjugate, pOEGMA-b-p(GFLG-Dendron-Ppa) (GFLG-DP), releases in response to cathepsin B (CTSB) after entering the tumor tissue. Dendritic-Ppa has a strong adsorption capacity to tumor cell membranes, which promotes efficient penetration and long-term retention. Lap can also be efficiently delivered to internal tumor cells to play its role due to the increased vesicle activity. Laser irradiation of Ppa-containing tumor cells results in production of intracellular ROS that is sufficient for inducing cell apoptosis. Meanwhile, Lap efficiently inhibits proliferation of remaining viable cells even in deep tumor regions, thus generating a significant synergistic anti-tumor therapeutic effect. This novel strategy can be extended to the development of efficient membrane lipid-based therapies to effectively combat tumors.

Nanoprobes that offer both fluorescence imaging (FI) and magnetic resonance imaging (MRI) can provide supplementary information and hold synergistic advantages. However, synthesis of such dual-modality imaging probes that simultaneously exhibit tunability of functional groups, high stability, great biocompatibility and desired dual-modality imaging results remains challenging. In this study, we used an amphiphilic block polymer from (ethylene glycol) methyl ether methacrylate (OEGMA) and N-(2-hydroxypropyl) methacrylamide (HPMA) derivatives as a carrier to conjugate a MR contrast agent, Gd-DOTA, and a two-photon fluorophore with an aggregation-induced emission (AIE) effect, TPBP, to construct a MR/two-photon fluorescence dual-modality contrast agent, Gd-DOTA-TPBP. Incorporation of gadolinium in the hydrophilic chain segment of the OEGMA-based carrier resulted in a high r1value for Gd-DOTA-TPBP, revealing a great MR imaging resolution. The contrast agent specifically accumulated in the tumor region, allowing a long enhancement duration for vascular and tumor contrast-enhanced MR imaging. Meanwhile, coupling TPBP with AIE properties to the hydrophobic chain segment of the carrier not only improved its water solubility and reduced its cytotoxicity, but also significantly enhanced its imaging performance in an aqueous phase. Gd-DOTA-TPBP was also demonstrated to act as an excellent fluorescence probe for two-photon-excited bioimaging with higher resolution and greater sensitivity than MRI. Since high-resolution, complementary MRI/FI dual-modal images were acquired at both cellular and tissue levels in tumor-bearing mice after application of Gd-DOTA-TPBP, it has great potential in the early phase of disease diagnosis.

ABSTRACTIntroductionSmall-molecular drugs are extensively used in cancer therapy, while they have issues of nonspecific distribution and consequent side effects. Nanomedicines that incorporate chemotherapeutic drugs have been developed to enhance the therapeutic efficacy of these drugs and reduce their side effects. One of the promising strategies is to prepare nanomedicines by harnessing the unique tumor microenvironment (TME).Areas coveredThe TME contains numerous cell types that specifically express specific antibodies on the surface. The physicochemical environment is characterized with a low pH, hypoxia, and a high redox potential resulting from tumor-specific metabolism. Therefore, intelligent nanomedicines designed based on the characteristics of the tumor microenvironment can be divided into two groups: the first group which is rapidly responsive to extracellular chemical/biological factors in the TME and the second one which actively and/or specifically targets cellular components in the TME.Expert opinionIn this paper, we review recent progress of nanomedicines by harnessing the TME and illustrate the principles and advantages of different strategies for designing nanomedicines, which are of great significance for exploring novel nanomedicines or translating current nanomedicines into clinical practice. We will discuss the challenges and prospects of preparing nanomedicines to utilize or alter the TME for achieving effective, safe anticancer treatment.

Sandwich structures are widely applied in modern industry such as aerospace, automobile as well as marine structures. However, the vibroacoustic properties of sandwich structures are adversely influenced by low effective mass. In this study, the flexural wave propagation characteristics and vibration mitigation performances of the periodic sandwich plate-type metastructures are investigated. The proposed sandwich plate-type metastructures are constituted of a sandwich plate with periodic thin-wall circular tube cores and periodically attached local stepped resonators. A finite element method combining Solid-Shell coupling numerical method and Bloch theory is presented to calculate the dispersion relations and the displacement fields of the eigenmodes of the infinite periodic sandwich plate-type metastructures. In addition, the acceleration frequency responses and vibration attenuation performances of finite periodic sandwich plate-type metastructures are numerically investigated and compared with the experimental measurements. Furthermore, the influences of geometric parameters on flexural wave band gaps are conducted. Results show that the sandwich plate-type metastructures can yield a low-frequency broad flexural wave band gap, in which the flexural wave propagation is conspicuously suppressed, resulting in significant flexural vibration attenuation. The flexural wave band gap and vibration attenuation performances can be effectively manipulated by designing geometric parameters of the sandwich plate-type metastructures.

A new integration concept for terahertz (THz) systems is presented in this article, wherein patterned silicon-oninsulator wafers form all DC, IF, and RF networks in a homogeneous medium, in contrast to existing solutions. Using this concept, silicon-micromachined waveguides are combined with silicon germanium (SiGe) monolithic microwave integrated circuits (MMICs) for the first time. All features of the integration platform lie in the waveguide's H-plane. Heterogeneous integration of SiGe chips is achieved using a novel in-line H-plane transition. As an initial step toward complete systems, we outline the design, fabrication, and assembly of back-to-back transition structures, for use at D-band frequencies (110-170 GHz). Special focus is given to the industrial compatibility of all components, fabrication, and assembly processes, with an eye on the future commercialization of THz systems. Prototype devices are assembled via two distinct processes, one of which utilizes semiautomated die-bonding tools. Positional and orientation tolerances for each process are quantified. An accuracy of ±3.5 μm, ±1.5° is achieved. Measured S-parameters for each device are presented. The insertion loss of a single-ended transition, largely due to MMIC substrate losses, is 4.2-5.5dB, with a bandwidth of 25 GHz (135-160 GHz). Return loss is in excess of 5 dB. Measurements confirm the excellent repeatability of the fabrication and assembly processes and, thus, their suitability for use in high-volume applications. The proposed integration concept is highly scalable, permitting its usage far into the THz frequency spectrum. This article represents the first stage in the shift to highly compact, low-cost, volume-manufacturable THz waveguide systems.

The quantum aspects of H motion in Nb are elucidated using the path integral simulation technique. We argue that the most important effect around 500 K can be viewed as a temperature and isotope dependent shift of the potential energy surface, and that treating the dynamics of H motion classically at that temperature is reasonable. The purely classical isotope effect is also determined but our molecular dynamics simulation data do not exhibit the “classical” isotope effect for the prefactor, D0∝ msu−1/2, owing to the more complicated diffusion behavior at high temperatures.

The synthesis of efficient porphyrin-based photosensitizers with intense near-infrared (NIR) absorption is in high demand for photodynamic therapy (PDT) but remains a challenging task. Herein we show the construction of a type of isoquinoline-fused porphyrins 3and 4with an impressive NIR-absorbing capacity. In light of the extraordinary singlet oxygen generation capabilities of 3upon NIR irradiation, the representative nanoparticles (3a-NPs) assembled show excellent tumoricidal behavior with good biocompatibility in the phototherapeutic window (650–850 nm).