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Structure-efficacy effect of small molecular drug attracts wide attentions, but it has always been ignored in nanomedicine research. To reveal the efficacy modulation of nanomedicine, we developed a new type of paclitaxel (PTX)-conjugated gold nanoparticles (PTX-conjugated GNPs) to investigate the influence of drug position in controlling their in vitro properties and in vivo performance. Two therapeutic ligands (TA-PEG-NH-N=PTX and TA-PTX=N-NH-PEG) were synthesized to conjugate PTX on the surface of GNPs at different positions, locating on the surface of gold conjugate and inserting between GNPs and polyethylene glycol (PEG, molecular weight 1000 Da), respectively. It was found that PEG-PTX@GNPs with PTX located between GNP and PEG exhibited higher aqueous solubility, biocompatibility, and stability. In addition, an acid sensitive hydrazone bond has been inserted between PTX and PEG in both ligands for drug release of PTX and PTX-PEG segment, respectively, at the tumor site. Further release of PTX from PTX-PEG segment is based on the esterase hydrolysis of an ester bond between PTX and PEG. This two-step drug release mechanism offers PEG-PTX@GNPs effective and sustained release behavior for desirable anticancer activity, enhanced therapeutic efficacy, and lower systematic toxicity in Heps-bearing animal models.

Drug target discovery is the basis of drug screening. It elucidates the cause of disease and the mechanism of drug action, which is the essential of drug innovation. Target discovery performed in biological systems is complicated as proteins are in low abundance and endogenous compounds may interfere with drug binding. Therefore, methods to track drug-target interactions in biological matrices are urgently required. In this work, a Fe3O4 nanoparticle-based approach was developed for drug-target screening in biofluids. A known ligand-protein complex was selected as a principle-to-proof example to validate the feasibility. After incubation in cell lysates, ligand-modified Fe3O4 nanoparticles bound to the target protein and formed complexes that were separated from the lysates by a magnet for further analysis. The large surface-to-volume ratio of the nanoparticles provides more active sites for the modification of chemical drugs. It enhances the opportunity for ligand-protein interactions, which is beneficial for capturing target proteins, especially for those with low abundance. Additionally, a one-step magnetic separation simplifies the pre-processing of ligand-protein complexes, so it effectively reduces the endogenous interference. Therefore, the present nanoparticle-based approach has the potential to be used for drug target screening in biological systems., Graphical abstract Image 1, Highlights • Fe3O4 NPs were made hydrophilic to adequately disperse in the cell lysate and fully contact with target proteins. • The magnetic property of the NPs allowed one-step isolation while maintaining ligand-protein non-covalent bindings. • It enabled the capture of low abundant targets in biological matrices while eliminated the endogenous interference.

In this study, a new type of traffic load test device was adopted to investigate the vibration isolation of layered sandbags under train load. The upper part of this device is composed of five high performance hydraulic actuators, to simulate the traffic load produced by train movement. First, sandbags were stacked on the subgrade, which were used as an active vibration isolation barrier. The variations of the soil stress, acceleration and vertical deformation of the sandbag subgrade were analysed by simulating different train speeds, and the relationship between the surface acceleration and train load was established. The attenuation of surface acceleration with depth was further analysed. Then, expanded polystyrene (EPS) foam plates with different thicknesses (placed at a certain distance from the subgrade) were used as a passive vibration isolation barrier. The vibration isolation effect of the EPS foam plate was also analysed. Results show that the sandbag layer used as a subgrade exhibited good vibration isolation effect. At a train load of 15 kN, the acceleration at a depth of 25 cm is less than that at the roadbed surface. The faster the train speed, the higher the acceleration attenuation rate.

In this study, the divergent behaviors were elucidated for CH2Cl2 and CH3Br oxidation over TiO2 and Ru/TiO2. Possible reaction mechanisms were analyzed. It was concluded that the adsorption and act...

Porous particles are widely used in liquid–solid and gas-liquid-solid reactors, and accurate prediction of drag coefficients ( C D ) for porous particles is essential for designing and optimizing these reactors. The drag coefficients for porous particles, however, have been mainly obtained via theoretical analysis and numerical simulations. Only three experimental studies were carried out to study the drag force on porous spherical particles due to the difficulties in the preparation of model porous spheres with a homogeneous porosity and homogeneous surface properties. In this paper, a method to prepare model porous spheres which have a homogeneous porosity and homogeneous surface properties with a good sphericity for a wider range of relative permeability β has been presented. The details of this method were documented, and it showed that the porous spheres constructed could withstand rigid collisions at the maximum terminal velocity of 1 m/s and keep the structure intact with a negligible quantity of binders. Then gravity-driven settling experiments of a single porous sphere by use of particle tracking velocimetry (PTV) method were carried out to evaluate the feasibility of the use of the prepared porous spheres. Experimental results for 12 porous spheres, with particle Reynolds number ( R e ) ranging from 1 to 108 and relative permeability β from 21.6 to 315.6, agreed well with the previous results in the literature. The porous particles prepared by our proposed method can be potentially used for measuring drag coefficients of the porous permeable spheres in a wider range of particle Reynolds number and permeability and studying the complex interaction between the porous particles and the surrounding fluid.

A low-order wavefront aberration self-compensation high power Nd:YAG slab laser module is developed and demonstrated. By numerical simulating the thermal distribution and transmission wavefront of the slab laser medium, a thermally-compensated heat removal geometry is developed to reduce the wavefront distortion. This method allows the non-uniform cooling to flatten the thermal gradient distribution in the width direction of the slab. By using the optimized gain module as an amplifier, the laser output power of 7.8 kW is achieved. Compared to the traditional module, the output power is 7.3 kW, and the peak-to-valley (PV) value of the wavefront distortion is reduced from 17.21 to $2.05~\mu \text{m}$ under full power, the beam quality factor $\beta $ is improved from 12.7 to 3.5 times diffraction limited while without additional correction system.

Growth factors (GFs) are versatile signalling molecules that orchestrate the dynamic, multi-stage process of wound healing. Delivery of exogenous GFs to the wound milieu to mediate healing in an active, physiologically-relevant manner has shown great promise in laboratories; however, the inherent instability of GFs, accompanied with numerous safety, efficacy and cost concerns, has hindered the clinical success of GF delivery. In this article, we highlight that the key to overcoming these challenges is to enhance the control of the activities of GFs throughout the delivering process. We summarise the recent strategies based on biomaterials matrices and molecular engineering, which aim to improve the conditions of GFs for delivery (at the 'supply' end of the delivery), increase the stability and functions of GFs in extracellular matrix (in transportation to target cells), as well as enhance the GFs/receptor interaction on the cell membrane (at the 'destination' end of the delivery). Many of these investigations have led to encouraging outcomes in various in vitro and in vivo regenerative models with considerable translational potential.

We report a new approach to effectively improve the optical-to-optical efficiency for quasi-continuous-wave (QCW) lasers by adjusting the pump pulse duration. During our single-slab laser test, an optical-to-optical conversion efficiency of 57% and a slope conversion of 67.8% are obtained with a maximum average output power of 7.3 kW, operating at a pulse repetition rate of 160 Hz with 470- $\mu \text{s}$ pulse duration. To the best of our knowledge, this represents the highest optical-to-optical efficiency for a QCW face-pumped Nd:YAG slab laser with such high power output ever reported.

This paper investigates a distributionally robust scheduling problem on identical parallel machines, where job processing times are stochastic without any exact distributional form. Based on a distributional set specified by the support and estimated moments information, we present a min-max distributionally robust model, which minimizes the worst-case expected total flow time out of all probability distributions in this set. Our model doesn’t require exact probability distributions which are the basis for many stochastic programming models, and utilizes more information compared to the interval-based robust optimization models. Although this problem originates from the manufacturing environment, it can be applied to many other fields when the machines and jobs are endowed with different meanings. By optimizing the inner maximization subproblem, the min-max formulation is reduced to an integer second-order cone program. We propose an exact algorithm to solve this problem via exploring all the solutions that satisfy the necessary optimality conditions. Computational experiments demonstrate the high efficiency of this algorithm since problem instances with 100 jobs are optimized in a few seconds. In addition, simulation results convincingly show that the proposed distributionally robust model can hedge against the bias of estimated moments and enhance the robustness of production systems.

Syringa oblata Lindl. (S. oblata) is a medicinal plant with effective broad-spectrum antibacterial activity, which can also inhibit Streptococcus suis biofilm formation. The processing of herbal medicine can purify medicinal materials, provide acceptable taste, reduce toxicity, enhance efficacy, influence performance and facilitate preparation. Thus, the aim of this study was to enhance the biofilm inhibition activity of S. oblata toward Staphylococcus xylosus (S. xylosus) using the best processing method. The content of rutin and flavonoids and the ability to inhibit the biofilm formation by S. oblata were examined using four processing methods. One of the best methods, the process of stir-frying S. oblata with vinegar, was optimized based on the best rutin content by response surface methodology. The histidine content and hisB gene expression of S. xylosus biofilm in vitro, resulting from stir-frying S. oblata with vinegar, were evaluated and were found to be significantly decreased and down-regulated, respectively. The results show that S. oblata stir-fried with vinegar can be used to effectively treat diseases resulting from S. xylosus infection. This is because it significantly inhibited S. xylosus biofilm formation by interfering with the biosynthesis of histidine; thus, its mechanism of action is decreasing histidine synthesis.

Heterostructures are a series of nanomaterials combining different components into a single nanostructure. Au-Fe3O4 heterostructures have received considerable attentions because of their superior properties coming from both individual and combinational features of gold and iron oxide nanoparticles. Their intrinsically peculiar magnetic, optical properties, and structure designability greatly enhance and broaden their potential applications in catalysis, assay, multimodal imaging, and synergistic treatment for tumor. In this review, we systematically introduce the preparation methods of Au-Fe3O4 heterostructures and their potential applications in the biomedical field, focusing on the unique synergistic effect caused by the combination of gold and iron oxide structures. This review will provide insights into the structure control in adjusting the function of heterogeneous or hybrid material, such as Au-Fe3O4 heterostructures, to implement their biomedical applications.

Bionics, involving biologically inspired structures and functions, applies the technology of lifeforms to manufactured objects. Synthesizing, modifying, and assembling gold nanoparticles (GNPs) utilizing biomolecules or biological ordered structures not only provide GNPs desirable biosafety and long-time circulation in vivo , but also offer them unique and superior performance in diagnosis and therapy. Therefore, in this review, we focus on the biosynthesis methods of GNPs inspired by marine mussel-imitated dopamine and its derivatives, the biomimetic surface modification of GNPs by various membranes, proteins, and peptides , and the assembly of GNPs on bioinspired template such as butterfly wing and nacre . The current biomedical applications using these biomimetic systems in catalysis, diagnosis, and drug delivery are also discussed, which provide understandings to the present GNP-based bioinspired nanomaterials and insights into the disciplines how to learn from nature.

Metal-organic frameworks (MOFs), especially those made by biological molecules (bio-MOFs), have been proved to be prospective candidates for biomedical applications. However, a simple and universal bio-MOF to load different substances for precise targeting is still lacking. In this work, we propose a facile one-pot method to prepare a peptide-doped bio-MOF for general encapsulation and targeted delivery. This bio-MOF is constructed by 9-fluorenylmethyloxycarbonyl-modified histidine (Fmoc-His) as a bridging linker that coordinates with Zn2+ ions, denoted as ZFH. The Fmoc-His-Asp-Gly-Arg peptide (Fmoc-HDGR) can be easily doped into the ZFH structure with different ratios to modulate the targeting ability of ZFH-DGR. Containing both hydrophobic Fmoc and hydrophilic His moieties, this framework is compatible with encapsulating various types of payloads, including hydrophobic chemotherapeutic, hydrophilic protein, and positively/negatively charged inorganic nanoparticles. It has also been proved to be highly biocompatible and stable in circulation, exhibit the capabilities to target ανβ3 integrin overexpressed on tumor cells, and trigger drug release in a low pH microenvironment at the tumor site. As a proof of concept, Doxorubicin (Dox)-loaded ZFH-DGR (ZFH-DGR/Dox) demonstrated high cell selectivity between liver hepatocellular carcinoma (HepG2) cells and normal liver (L02) cells, which express high and low ανβ3 integrin, respectively. This selectivity endows ZFH-DGR/Dox precise treatment and low toxicity in Heps-bearing liver cancer mice. This work develops a de novo approach to construct a peptide-doped bio-MOF system for universal load, precise delivery, and peptide drug combination therapy in the future.

Manganese oxides with varied Mn valance states but identical morphologies were synthesized via a facile thermal treatment of γ-MnOOH. Also, their catalytic performance on ozone decomposition was investigated following the order of Mn3O4 < Mn2O3 < MnO2 < MnO2-H-200. In combination with X-ray diffraction (XRD), scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET), transmission electron microscopy (TEM), H2-temperature-programmed reduction (TPR), O2-temperature-programmed desorption (TPD), and X-ray photoelectron spectroscopy (XPS) characterization, it was deduced that the superior O3 decomposition capacity for MnO2-H-200 was strongly associated with abundant oxygen vacancies on its surface. Among Mn3O4, Mn2O3, and MnO2, the difference in O3 decomposition efficiency was dependent on the divergent nature of oxygen vacancy. Density functional theory (DFT) calculation revealed that Mn3O4 and MnO2 possessed lower formation energy of oxygen vacancy, while MnO2 had the minimum desorption energy of peroxide species (O2*). It was deduced that the promotion of the O3 decomposition capability was attributed to the easier O2* desorption. Insights into the deactivation mechanism for MnO2-H-200 further validated the assumptions. As the reaction proceeded, adsorbed oxygen species accumulated on the catalyst surface, and a portion of them were transformed to lattice oxygen. The consumption of oxygen vacancy led to the deactivation of the catalyst.

Metal–organic frameworks (MOFs) are built using various organic ligands and metal ions (or clusters). With properties of high porosity, tunable chemical composition, and potential for post-synthetic modification, they have been applied in biomedicine, especially in bio-sensing, bio-imaging, and drug delivery. Since organic ligands and metal centers (ions or clusters) in the structure of MOFs can directly influence the property, function, and performance of MOFs, strict screening of organic ligands and metal centers is necessary. Especially, to improve the application of MOFs in the field of biomedicine, biocompatible organic ligands with low toxicity are desirable. In recent years, biological metal–organic frameworks (bio-MOFs) with ideal biocompatibility and diverse functionality have attracted wide attention. Endogenous biomolecules, including nucleobases, amino acids, peptides, proteins, porphyrins and saccharides, are employed as frameworks for MOF construction. These biological ligands coordinate with diverse metal centers in different ways, leading to the structural diversity of bio-MOFs. In this review, we summarize the organic ligand selectivity in constructing different types of bio-MOFs and their influence in biomedical applications with attractive new functions.

Macrophages play an important role in the body's immune defense process. Phenotype imbalance between M1 and M2 macrophages induced by inflammation-related disorders and tumor can also be reversibly converted to treat these diseases. As exogenous substances, a large part of gold-based nanomaterials interact with macrophages once they enter the body, which provides gold nanomaterials a huge advantage to act as imaging contrasts, active substance carriers, and therapeutic agents for macrophage modulation. By cutting off macrophage recruitment, inhibiting macrophage activities, and modulating M1/M2 polarization, gold nanomaterial engineering exerts therapeutic effects on inflammation-related diseases at target sites. In this review, biological functions of macrophages in inflammation-related diseases are introduced, the effect of physicochemical factors of gold nanomaterials including size, shape, and surface chemistry is focused on the interaction between macrophages and gold nanomaterials, and the applications of gold nanomaterials are elaborated for tracking and treating these diseases by macrophages. The rational and smart engineering of gold nanomaterials allows a promising platform for macrophage-mediated inflammation and tumor imaging and treatment.

In this study, Boit wave theory and Snell’s law were used to deduce the transmission coefficients of waves in saturated sandy soil passing through elastic barriers. The theoretical equations were verified using previously published results and experimental data. At the same time, a series of indoor model tests was used to investigate the vibration reduction of an in-filled barrier under vertical excitation. The vibration reduction effect of the barrier is evaluated by measuring vibration amplitude at a measuring point, in either the presence or absence of a barrier. The effects of barrier geometry and material properties on the vibration reduction effect were systematically studied. Our experimental results show that a barrier can reduce the vibration amplitude of the protected area. Concrete barriers and foam barriers have different vibration reduction mechanisms, and enlargement will occur at the rear of the concrete barrier. Additionally, a new type of tooth-shaped vibration reduction barrier is proposed. The experimental results show that this barrier can effectively reduce vibration.

This paper is concerned with a binary detection problem over a nonsecure network. To satisfy the communication constraint and against possible cyber attacks, which are modeled as jamming signals injected to the network, a likelihood ratio based (LRB) scheduler is designed in the sensor to smartly select informative sensor measurements for transmission. We show that even under a moderate transmission rate constraint of secure networks, an optimal LRB scheduler can achieve a comparable asymptotic detection performance to the standard Neyman–Pearson test using the full set of measurements, and is strictly better than the random scheduler. For nonsecure networks, the LRB scheduler can also maintain the detection functionality but suffers graceful performance degradation under different attack intensities. Finally, we perform simulations to validate our theoretical results.

Studies on the influence of one critical parameter (e.g., size), targeting a specific disease, while keeping other factors unchanged, are important for improving understanding and application of the molecular design of biomedical nanomaterials. In this study, we used doxorubicin (Dox)-conjugated gold nanoparticles (GNPs) to investigate the effects of the size of the gold core (10, 20, or 60 nm) on the performance of their conjugates. We found that all three conjugates differed slightly in their physicochemical properties, facilitating a direct and accurate assessment of the size effects of GNP-Dox conjugates on their in vitro and in vivo performance. The cytological properties (the cell penetration rate and efficiency, as well as the cytotoxicity) and antitumor performance (the intratumoral penetration, treatment efficacy, and biodistribution) were highly correlated to the size of the inorganic core. Among all test groups, although the conjugate with a 60-nm gold core had the highest drug loading and release efficiency, the conjugate with a 10-nm gold core displayed the best antitumor efficacy toward the liver cancer models. This was because it showed the deepest tumor permeability and the highest tumor cell-killing ability of Dox transported by the relatively small GNPs. This study provides important evidence for better understanding the effect of size on in vitro and in vivo properties of potential therapeutic nanosystems and their structure design.

Gold nanoparticles (GNPs) are one of the most widely studied and utilized materials in nanomedicine, but there is no business or national quality standard for their medicinal applications. This has become the bottleneck in the translation of clinical applications of gold-based nanomaterials. To solve this issue, the most frequently used citrate-reduced GNPs were selected as demonstration in this study to conduct quality standard research. The different molar ratios of chloroauric acid to trisodium citrate in preparation were changed, from 1:1 to 1:5, to adjust the particle size and main ingredients in gold colloids. The compositions of reduced Au0 and residual Au3+ were determined by X-ray photoelectron spectroscopy (XPS), inductively coupled plasma–atomic emission spectroscopy (ICP-AES), and photodynamic catalysis, while the residual citrate and its oxidation products in supernatants were detected by nuclear magnetic resonance (1H NMR) spectroscopy and nonaqueous titration. Cell viability of human normal...

Chitosan (CS), a kind of naturally produced polysaccharide with extraordinary biocompatibility and biodegradation, shows much potential to act as reducing and stabilizing agent in the synthesis of gold nanoparticles (AuNPs) for drug delivery. To solve the poor solubility and expand the pharmaceutical applications of CS, various CS derivatives through rational design have been developed and further used to prepare, stabilize, and mediate self-assembling of gold materials. Herein, we chose sulfonic chitosan as a stabilizing reagent for the synthesis of highly stable AuNPs (AuNP/SCSs) with diameters of about 3 nm. For investigating their surface electronic payload of charged drugs, the negatively charged fluorescence isothiocyanate (FITC) and positively charged Rhodamine B (Rb) were used as models to be modified on the surface of the AuNP/SCSs via a layer-by-layer (LbL) method. With a basis of the fluorescence resonance energy transfer (FRET) principle, via adjusting the distance between AuNPs and fluorescent molecules by tuning the layers of charged polymers, the regulation of the fluorescence intensity of the fluorescent molecules has been achieved. In addition, the drug loading efficiency was investigated.

The aim of the present investigation was to enhance the solubility, dissolution, and oral bioavailability of praziquantel (PZQ), a poorly water-soluble BCS II drug (Biopharmaceutical Classification System), using a solid dispersion (SD) technique involving hydrophilic copolymers. The SD formulations were prepared by a solvent evaporation method with PZQ and PEG 4000 (polyethylene glycol 4000), PEG 6000, or P 188 polymers at various weight ratios or a combination of PEG 4000/P 188. The optimized SD formulation, which had the highest solubility in distilled water, was further characterized by its surface morphology, crystallinity, and dissolution in 0.1 M HCl with 0.2% w/v of sodium dodecyl sulfate (SDS). X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) revealed the amorphous form of PZQ in the SDs. Moreover, at an oral dosage of 5 mg/kg PZQ, the SDs had higher Cmax values and areas under the curve (AUCs) compared to those of commercial PZQ tablets. Preparation of PZQ-loaded SDs using PEG 4000/P 188 is a promising strategy to improve the oral bioavailability of PZQ.

Metal-organic frameworks (MOFs) have been successfully used as efficient quenchers for fluorescent DNA detection. However, the surface charge property of MOFs can inevitably affect their fluorescence quenching behavior. Herein, nanoscale MOFs (NMOFs), including MOF nanosheets and nanoparticles, have been employed to investigate the relationship between the fluorescence quenching and surface properties of NMOFs. We find that the positively and negatively charged NMOFs exhibited totally opposite fluorescence quenching properties toward negatively charged FAM-labeled double-stranded DNA (dsDNA). On the contrast, they show negligible influence on the sensing of positively charged TAMRA-labeled dsDNA. This study provides a new insight of the fluorescence quenching property of NMOFs and offers a new concept for construction of ratiometric fluorescence DNA biosensors.

Imaging-guided photothermal therapy (PTT) by combination of imaging and PTT has been emerging as a promising therapeutic method for precision therapy. However, the development of multicomponent nanoplatforms with stable structures for both PTT and multiple-model imaging remains a great challenge. Herein, we synthesized monodisperse Au-Fe2C Janus nanoparticles (JNPs) of 12 nm, which are multifunctional entities for cancer theranostics. Due to the broad absorption in the near-infrared range, Au-Fe2C JNPs showed a significant photothermal effect with a 30.2% calculated photothermal transduction efficiency under 808 nm laser irradiation in vitro. Owing to their excellent optical and magnetic properties, Au-Fe2C JNPs were demonstrated to be advantageous agents for triple-modal magnetic resonance imaging (MRI)/multispectral photoacoustic tomography (MSOT)/computed tomography (CT) both in vitro and in vivo. We found that Au-Fe2C JNPs conjugated with the affibody (Au-Fe2C-ZHER2:342) have more accumulation and deeper penetration in tumor sites than nontargeting JNPs (Au-Fe2C-PEG) in vivo. Meanwhile, our results verified that Au-Fe2C-ZHER2:342 JNPs can selectively target tumor cells with low cytotoxicity and ablate tumor tissues effectively in a mouse model. In summary, monodisperse Au-Fe2C JNPs, used as a multifunctional nanoplatform, allow the combination of multiple-model imaging techniques and high therapeutic efficacy and have great potential for precision theranostic nanomedicines.

Intraorgan targeting of chemical drugs at tumor tissues is essential in the treatment of solid tumors that express the same target receptor as normal tissues. Here, asialoglycoprotein receptor (ASGP-R)-targeting paclitaxel-conjugated gold nanoparticles (Gal/PTX-GNPs) are fabricated as a demonstration to realize the precise treatment of liver cancer. The enhanced biological specificity and therapeutic performance of drugs loaded on nanoparticles not only rely on the ligands on carriers for receptor recognition but are also determined by the performance of gold conjugates with designed structure. The tumor cell selectivity of the designed conjugates in liver tumor (HepG2) cells is close to six times of that incubated with control conjugates without galactose modification in liver normal (L02) cells. The drug level in tumor versus liver of Gal/PTX-GNPs is 121.0% at 8 h post injection, a 15.7-fold increase in the tumor specificity compared to that of GNPs conjugated with PTX only. This intraorgan-targeting strategy results in a considerable improvement of performance in treating both Heps heterotopic and orthotopic xenograft tumor models, which is expected to be used for the enhanced antitumor efficacy and reduced hepatotoxicity in liver cancer treatment.

This work concentrates on the improvement of LaMnO3 perovskite catalysts for methane combustion by an effective and mild citric acid etching strategy. The etched catalysts showed improved catalytic activity due to higher surface area, abundant vacancies, higher surface Mn4 +/Mn3 + ratio and more active oxygen species. Furthermore, the pre-treated catalysts maintained good stability because of the maintenance of perovskite structure.

Drug-conjugated gold nanoparticles (GNPs), which are generally constructed with many molecules of thiol-terminated polyethylene glycol (PEG)-drug decorated on their surfaces via a thiol-Au covalent bond, are promising and efficient nanoprodrugs. However, because of the exposure of the hydrophobic drug molecules on the surface of the conjugate, in vivo stability, opsonization, and subsequent inefficient therapy become the main issues of this system. To solve these problems without complicating the structures of gold conjugates, herein we propose a method to change the relative position of PEG and the drug. A novel gold conjugate (GNP-NHN═Dox-mPEG) with doxorubicin (Dox) shielded by PEGylation on the surface of GNPs is designed. It demonstrates improved solubility, stability, and dispersion and achieves a two-step stimulus-responsive drug release in response to an acidic environment in lysosomes and then esterase in the cytoplasm. This unique manner of release enables the cytoplasm to act as a reservoir for sustained drug delivery into the nucleus to improve antitumor efficacy in vivo. The intratumoral drug concentrations of the conjugate reach 14.4 ± 1.4 μg/g at 8 h, a two-fold increase in the drug concentration compared with that of the doxorubicin hydrochloride group. This molecular design and regulation approach is facile but important in modulating the in vivo performance of nanovehicles and demonstrates its vital potential in developing effective nanoparticle-based drug delivery agents.

Although combination delivery (co-delivery) shows much superiority in the defect compensation of single-agent therapy, the construction and application of co-delivery systems are still challenging, especially for protein-based joint systems. In this work, a series of chitosan (CS)-amino acid derivatives (Arg-CS, Lys-CS, and Phe-CS) with different degrees of substitution (DS) were synthesized to prepare CS nanocapsules (CNCs) using a simple emulsification method in the presence of linoleic acid (LA). The hydrophobic drug can be loaded in LA droplets, and a positively charged protein stabilized the optimized Arg-CS nanocapsules (Arg-CNCs) on their negative surfaces. The in vitro antitumor efficacy of Arg-CNCs co-delivering paclitaxel and recombinant human caspase-3 was evaluated in HeLa cells. The co-delivery system displayed much lower IC50 values and a higher percentage of apoptotic cells compared with the control groups. This system provides a promising and universal strategy for co-delivery, leading to collaborative tumor treatment.

Firstly, the spinel cobalt oxide (Co3O4) was controllably synthesized with different morphologies (cubical, flower-like, plate-like and rectangular-like) via a hydrothermal method. Then Pd was loaded on them by incipient wetness impregnation. The properties of the samples prepared were characterized by XRD, H2-TPR, CO-TPR, SEM, TEM, HRTEM and XPS. The impacts of Pd addition on CH4 and CO oxidation were investigated under lean methane and CO atmosphere, respectively. The effectiveness of Pd was different for CH4 and CO oxidation. For methane oxidation, the activities of Co3O4 were enhanced due to Pd loading. And the orders of activity primarily kept consistent before and after impregnation, while the extent of improvement on activity from Co3O4 to Pd/Co3O4 was consistent with the order of surface Oads/Olat of Pd/Co3O4, indicating that different interaction occurred between Pd species unit cell and the Co3O4 unit cell with different crystal planes. In the case of CO oxidation, a significant decline on activity was observed over the Pd/Co3O4-R (rectangular-like Co3O4), Pd/Co3O4-F (flower-like Co3O4), Pd/Co3O4-P (plate-like Co3O4), while a distinct promotion on activity was observed over the Pd/Co3O4-C (cubical Co3O4). Similarly the variations in the activity of Pd/Co3O4 were ascribed to the shifts on surface Oads/Olat molar ratio and the specific area reaction rate.

This paper presents a distributionally robust (DR) optimization model for the single machine scheduling problem (SMSP) with random job processing time (JPT). To the best of our knowledge, it is the first time a DR optimization approach is applied to production scheduling problems in the literature. Unlike traditional stochastic programming models, which require an exact distribution, the presented DR-SMSP model needs only the mean-covariance information of JPT. Its aim is to find an optimal job sequence by minimizing the worst-case Conditional Value-at-Risk (Robust CVaR) of the job sequence’s total flow time. We give an explicit expression of Robust CVaR, and decompose the DR-SMSP into an assignment problem and an integer second-order cone programming (I-SOCP) problem. To efficiently solve the I-SOCP problem with uncorrelated JPT, we propose three novel Cauchy-relaxation algorithms. The effectiveness and efficiency of these algorithms are evaluated by comparing them to a CPLEX solver, and robustness of the optimal job sequence is verified via comprehensive simulation experiments. In addition, the impact of confidence levels of CVaR on the tradeoff between optimality and robustness is investigated from both theoretical and practical perspectives. Our results convincingly show that the DR-SMSP model is able to enhance the robustness of the optimal job sequence and achieve risk reduction with a small sacrifice on the optimality of the mean value. Through the simulation experiments, we have also been able to identify the strength of each of the proposed algorithms.

Mixed Integer Programming (MIP) is one of the most widely used modeling techniques for combinatorial optimization problems. In many applications, a similar MIP model is solved on a regular basis, maintaining remarkable similarities in model structures and solution appearances but differing in formulation coefficients. This offers the opportunity for machine learning methods to explore the correlations between model structures and the resulting solution values. To address this issue, we propose to represent a MIP instance using a tripartite graph, based on which a Graph Convolutional Network (GCN) is constructed to predict solution values for binary variables. The predicted solutions are used to generate a local branching type cut which can be either treated as a global (invalid) inequality in the formulation resulting in a heuristic approach to solve the MIP, or as a root branching rule resulting in an exact approach. Computational evaluations on 8 distinct types of MIP problems show that the proposed framework improves the primal solution finding performance significantly on a state-of-the-art open-source MIP solver.

Nitric oxide (NO) induces a multitude of antitumor activities, encompassing the induction of apoptosis, sensitization to chemo-, radio-, or immune-therapy, and inhibition of metastasis, drug resistance, angiogenesis, and hypoxia, thus attracting much attention in the area of cancer intervention. To improve the precise targeting and treatment efficacy of NO, a glutathione (GSH)-sensitive NO donor (1,5-bis[(l-proline-1-yl)diazen-1-ium-1,2-diol- O2-yl]-2,4-dinitrobenzene, BPDB) coordinates with iron ions to form the nanoscale coordination polymer (NCP) via a simple precipitation and then partial ion exchange process. The obtained Fe(II)-BNCP shows desirable solubility, biocompatibility, and circulation stability. Quick NO release triggered by high concentrations of GSH in tumor cells improves the specificity of NO release in situ, thus avoiding side effects in other tissues. Meanwhile, under high concentrations of H2O2 in tumors, Fe2+ ions in BPDB-based NCP, named Fe(II)-BNCP, exert Fenton activity to generate hydroxyl radicals (·OH), which is the main contribution for chemodynamic therapy (CDT). In addition, ·O2- generated by the Haber-Weiss reaction of Fe2+ ions with H2O2 can quickly react with NO to produce peroxynitrite anion (ONOO-) that is more cytotoxic than ·O2- or NO only. This synergistic NO-CDT effect has been proved to retard the tumor growth in Heps xenograft ICR mouse models. This work not only implements a synergistic effect of NO-CDT therapy but also offers a simple and efficient strategy to construct a coordination polymer nanomedicine via rationally designed prodrug molecules such as NO donors.

We synthesized chitosan grafted with β-cyclodextrin (CD-g-CS) from mono-6-deoxy-6-(p-toluenesulfonyl)-β-cyclodextrin and chitosan. Two different amounts of immobilized β-cyclodextrin (β-CD) on CD-g-CS (QCD: 0.643 × 103 and 0.6 × 102 μmol/g) were investigated. The results showed that the amino contents of CD-g-CS with QCD = 0.643 × 103 and 0.6 × 102 μmol/g were 6.34 ± 0.072 and 9.41 ± 0.055%, respectively. Agar diffusion bioassay revealed that CD-g-CS (QCD = 0.6 × 102 μmol/g) was more active against Staphylococcus xylosus and Escherichia coli than CD-g-CS (QCD = 0.643 × 103 μmol/g). Cell membrane integrity tests and scanning electron microscopy observation revealed that the antimicrobial activity of CD-g-CS was attributed to membrane disruption and cell lysis. Uptake tests showed that CD-g-CS promoted the uptake of doxorubicin hydrochloride by S. xylosus, particularly for CD-g-CS with QCD = 0.6 × 102 μmol/g, and the effect was concentration dependent. CD-g-CS (QCD = 0.6 × 102 and 0.643 × 103 μmol/g) also improved the aqueous solubilities of sulfadiazine, sulfamonomethoxine, and sulfamethoxazole. These findings provide a clear understanding of CD-g-CS and are of great importance for reducing the dosage of antibiotics and antibiotic residues in animal-derived foods. The results also provide a reliable, direct, and scientific theoretical basis for its wide application in the livestock industry.

This paper proposes a distributionally robust chance constrained (DRCC) model to handle the daily small disruptions in steelmaking and continuous casting process. The processing time of each charge is assumed to be a random variable belonging to an ambiguous distribution set which is described by support set, mean and variance information. The proposed DRCC model aims to minimize the objective function and at the same time ensure each constraint is established with a certain probability, i.e., distributionally robust individual chance constrained (DRICC) model, or all constraints together are established with a certain probability, i.e., distributionally robust joint chance constrained (DRJCC) model even when the uncertain parameters are in their worst cases. We transform DRICC model into a linear programming model and propose an iterative improvement method to tackle the DRJCC model. To test the robustness of the models, we evaluate the obtained robust schedules under different distributions of the processing time. Experimental results show that both DRCC models are able to provide more robust schedules than compared to the deterministic model.

CH3Br catalytic oxidation as the probe reaction was investigated over Ru supported on TiO2 with different crystalline phases. 1% Ru/anatase TiO2 (a-TiO2) exhibited superior stability at 240 °C after a 180 h time-on-stream run. And there was an induced activation for 1% Ru/a-TiO2 during the initial 60 h reaction. Then the activity sustained stable. To elucidate the intrinsic mechanism, a series of characterizations were performed such as XRD, CO-Pulse, H2-TPR, XPS and NH3-TPD etc. Results showed that the Ru particle size increased and the Ru0 content decreased as the reaction proceeded, which were not conductive to the reaction. It was assumed that the catalytic activity was strongly dependent on other factors. In combination with NH3-TPD and Py-FTIR measurements, it was confirmed that the enhanced activity and stability was strongly associated with the surface acidity, especially moderate strong Lewis acid (L acid). The increase of the acid amount and acidity strength was led by the generation and adsorption of HBr, Br2 and RuOxBry during the reaction, among which HBr and Br2 was easier to desorb at 250 °C. While moderate strong L acid was sourced from the formation of RuOxBry. The addition of transition metal (Ce, Co, Mn, Nb and Ni) further validated that the moderate strong L acid played a decisive role in the CH3Br catalytic oxidation.

The industrial sector is one of the largest energy consumers in the world. To alleviate the grid’s burden during peak hours, time-of-use (TOU) electricity pricing has been implemented in many countries around the globe to encourage manufacturers to shift their electricity usage from peak periods to off-peak periods. In this paper, we study the unrelated parallel machine scheduling problem under a TOU pricing scheme. The objective is to minimize the total electricity cost by appropriately scheduling the jobs such that the overall completion time does not exceed a predetermined production deadline. To solve this problem, two solution approaches are presented. The first approach models the problem with a new time-interval-based mixed integer linear programming formulation. In the second approach, we reformulate the problem using Dantzig–Wolfe decomposition and propose a column generation heuristic to solve it. Computational experiments are conducted under different TOU settings and the results confirm the effectiveness of the proposed methods. Based on the numerical results, we provide some practical suggestions for decision makers to help them in achieving a good balance between the productivity objective and the energy cost objective.

Recently, there has been an increasing concern on the carbon efficiency of the manufacturing industry. Since the carbon emissions in the manufacturing sector are directly related to the energy consumption, an effective way to improve carbon efficiency in an industrial plant is to design scheduling strategies aiming at reducing the energy cost of production processes. In this paper, we consider a permutation flow shop (PFS) scheduling problem with the objectives of minimizing the total carbon emissions and the makespan. To solve this multi-objective optimization problem, we first investigate the structural properties of non-dominated solutions. Inspired by these properties, we develop an extended NEH-Insertion Procedure with an energy-saving capability. The accelerating technique in Taillard’s method, which is commonly used for the ordinary flowshop problem, is incorporated into the procedure to improve the computational efficiency. Based on the extended NEH-Insertion Procedure, a multi-objective NEH algorithm (MONEH) and a modified multi-objective iterated greedy (MMOIG) algorithm are designed for solving the problem. Numerical computations show that the energy-saving module of the extended NEH-Insertion Procedure in MONEH and MMOIG significantly helps to improve the discovered front. In addition, systematic comparisons show that the proposed algorithms perform more effectively than other tested high-performing meta-heurisitics in searching for non-dominated solutions.

To improve current cancer treatment efficacy, a method for early and accurate detection is of great importance, especially for cancer biomarkers with a specific theranostic target. Matrix metalloproteases (MMPs) are a family of endopeptidases that are highly expressed in various types of cancers and play an important role inmetastasis. To detect and locate over-expressed MMPs in vitro and in vivo, a fluorescent “off–on” nanoswitch (GNP-p-FITC/mPEG) has been developed by engineering the fluorescein isothiocyanate-labeled peptide (p-FITC) and thiolated polyethyleneglycol monomethyl ether (HS-mPEG, molecular weight 2000 Da) on the surface of gold nanoparticles (GNPs). The p-FITC contains a MMP preferential cleavage site and HS-mPEG is used to improve the stability and biocompatibility of the nanoswitch in vivo. The nanoswitch has a very low background signal and displays sensitive response to compound enzymes (containing MMP-2, MMP-4, and MMP-9 that may contribute to MMPs activity) either in vitro or in vivo. As a result of using GNPs, the nanoswitch has enhanced cellular internalization with HepG2 cells due to the endocytosis process as well as improved tumor penetration performance due to its small-size-induced enhanced permeability and retention (EPR). Furthermore, the biocompatibility and tumor targeting ability of the nanoswitch are established by its cytotoxicity with HepG2 cells and distributions in normal organs and tumor tissues. The simple preparation process, the complete fluorescence quenching, and the effective fluorescence recovery (about 50-fold intensity) makes the present MMP-responsive nanoswitch an accurate diagnosis probe for mapping MMPs and evaluating the tumor development both in vitro and in vivo.

Hybrid drug delivery system containing both organic and inorganic nanocarriers is expected to achieve its complementary advantages for the aim of improving the performance of antineoplastic drugs in tumor therapy. Here we report the use of liposomes and gold nanoparticles to construct a liposome with a hybrid Cluster Bomb structure and discuss its unique multi-order drug release property for liver tumor treatment. A very simple method is used for the hybrid liposome preparation and involves mixing two solutions containing liposomes loaded with either non-covalent or covalent Paclitaxel (PTX, namely free PTX or PTX-conjugated GNPs, respectively) by different ratio of volume (25:75, 50:50, 25:75, v/v). Various mixed liposomes were tested to determine the optimal conditions for maximum drug delivery. The optimized liposome was then tested using xenograft Heps tumor-bearing mice and showed the best efficacy for chemotherapeutic inhibition of tumor at PTX liposome: PTX-conjugated GNP liposome of 25:75 ratio (v/v). This system allows for simple and easy preparation while providing a more accurate site- and time-release mode for tumor treatment using antitumor drugs.

An adjustable slab-aberration compensator (ASAC) with the ability to compensate the large magnitude inherent wavefront aberrations in the slab width direction is proposed and experimentally demonstrated. The ASAC has a size of 130mm×45mm (effective aperture of 75mm×28mm) and 11 actuators along the length with a contact spacing of 8 mm. The design is optimized by simulations in terms of the mirror’s coupling coefficient with the contact areas, mechanical properties of the driving units, and the mirror thickness. The initial surface figure of the ASAC has PV and RMS values of 55 nm and 10 nm, and the dynamic range is 30 µm. In our experiments, a 20 kW Nd: YAG quasi-continuous wave (QCW) slab laser is further compensated by the ASAC system. The beam quality increases from 15× to 3.5× diffraction limit at 20 kW output after correction. Besides, the proposed ASAC can maintain the surface shape after power shutdown and have good thermal stability. The temperature rise of the ASAC is less than 7 °C in the 20 kW laser correction experiment.

One of the difficulties in the translation of gold nanoparticles (GNPs) into clinical practice is the formation of the protein corona (PC) that causes the discrepancy between the in vitro and in vivo performance of GNPs. The PC formed on the surface of GNPs gives them a biological identity instead of an initial synthetic one. In most instances, this biological identity increases the particle size, leads to more clearance by the reticuloendothelial system, and causes less uptake by target cells. However, the performance of GNPs can still be improved by rewriting their original surface chemistry via the PC. This review specifically focuses on discussing the main influence factors, including the biological environment and physicochemical properties of GNPs, which affect the production and status of the PC. The status of the PC such as the amount, thickness, and composition subsequently influence the biological behavior of GNPs, especially their cellular uptake, cytotoxicity, biodistribution, and tumor targeting. Further understanding and revealing the impacts of the PC on the biological behavior of GNPs can be a promising and important strategy to regulate and improve the performance of GNP-based biosystems in the future.

A 24.6 kW quasi-continuous-wave (QCW) Nd-doped yttrium aluminum garnet (Nd:YAG) slab laser is proposed in this Letter. The laser is based on a stable–unstable hybrid cavity. A stable and an unstable resonator were constructed along orthogonal directions in the aperture of the slab. Due to features of the hybrid cavity, the slab laser achieves both high efficiency of power extraction with excellent beam quality and compactness with simplicity. Average output power of 24.6 kW with 47% optical-to-optical efficiency is achieved in the experiment. The beam quality of the output beam is 1.5 times diffraction limits after correction of adaptive optics. The repetition frequency and pulse width of the laser are 400 Hz and 200 μs.

Catalytic combustion of methane was studied over Ce0.5Zr0.5O2 and CeO2 supported Pd (Pd/CZ and Pd/Ce) catalysts in the presence of SO2. The effect of sulfation (air including 100 ppm SO2 for 6 h at 500 °C) on the sulfur-tolerant performance of the catalysts was also investigated. Results indicated that there is a considerable promotion effect for CH4 complete oxidation on Pd/CZ catalyst, while the activity of Pd/Ce catalyst was inevitably inhibited. Further, the superior sulfur-tolerant behavior of Pd/CZ was verified through a 50 h time-on-stream stability test. Mechanistic insights into the synergistic effect between the support and Pd were unveiled by Raman, H2-TPR, XPS, NH3-TPD, DRIFTS, HAADF-STEM, etc. It was deduced that the formation of sulfates at the Pd-support interface could promote the dissociative adsorption of methane on Pd/CZ catalyst. Meanwhile, the higher relative acid strength and the acid amount were also decisive factors for the high sulfur-resistant performance. The enhanced acid strength and acid amount prevented the further formation of bulk-like sulfate species for the SO2 treated Pd/CZ catalyst, thus enhancing the sulfur-tolerant ability of the catalyst.

The unique physicochemical properties of silver nanoparticles offer a large potential for biomedical application, however, the serious biotoxicity restricts their usage. Herein, nanogalvanic couple Ag–Fe@Fe3O4 heterostructures (AFHs) are designed to prevent Ag+ release from the cathodic Ag by sacrificial anodic Fe, which can reduce the cytotoxicity of Ag. AFHs are synthesized with modified galvanic displacement strategy in nonaqueous solution. To eliminate the restriction of lattice mismatch between Fe and Ag, amorphous Fe@Fe3O4 nanoparticles (NPs) are selected as seeds, meanwhile, reductive Fe can reduce Ag precursor directly even at as low as 20 °C without additional reductant. The thickness of the Fe3O4 shell can influence the amorphous properties of AFHs, and a series of Janus‐ and satellite‐like AFHs are synthesized. A “cut‐off thickness” effect is proposed based on the abnormal phenomenon that with the increase of reaction temperature, the diameter of Ag in AFHs decreases. Because of the interphase interaction and the coupling effect of Ag and Fe@Fe3O4, the AFHs exhibit unique optical and magnetic properties. This strategy for synthesis of monodisperse heterostructures can be extended for other metals, such as Au and Cu.

This paper proposes new block properties for the flowshop scheduling problem with blocking to minimise makespan. A pruning procedure based on these proposed properties is used in the construction phase of an iterated greedy algorithm to decrease the total number of solutions to be examined to find an optimal schedule. Computational results using Taillard’s benchmark problem instances show that the new block properties help to eliminate more ‘unpromising’ solutions than the classic properties. In addition, the effectiveness of the proposed algorithm is verified by comparison with some high-performing algorithms for the considered problem.

In this letter, a high pulse energy and high beam quality 819.7 nm Ti:sapphire laser pumped by a frequency-doubled Nd:YAG laser is demonstrated. At incident pump energy of 774 mJ, the maximum output energy of 89 mJ at 819.7 nm with a pulse width of 100 μs is achieved at a repetition rate of 5 Hz. To the best of our knowledge, this is the highest pulse energy at 819.7 nm with pulse width of hundred microseconds for a Ti:sapphire laser. The beam quality factor M 2 is measured to be 1.18. This specific wavelength with the high pulse energy and high beam quality at 819.7 nm is a promising light source to create a polychromatic laser guide star together with a home-made 589 nm laser via exciting the sodium atoms in the mesospheric atmosphere.

We demonstrate a high power, high brightness, slab amplifier based on face-pumped Nd:YAG slab gain modules, having a high efficient hybrid cooling system of the conduction cooling and forced convection cooling. Using a single gain module, a laser output power up to 4.5 kW with a remarkable optical-optical conversion efficiency of 51% is realized, indicating an excellent lasing performance of the Nd:YAG slab module. The amplifier operates at a repetition rate of 700 Hz and delivers a maximum average output power exceeding 10.5 kW with pulse duration of 150 μs. A good beam quality factor is measured to be β = 1.9. To the best of our knowledge, this is the highest brightness for a 10 kW level Nd:YAG slab amplifier.

In this Letter, a 10.8 kW, 2.6 times diffraction limited laser based on a continuous wave (CW) Nd:YAG oscillator using an unstable resonator and an extra-cavity adaptive optics system was presented. Two Nd:YAG slabs and a disk-laser configuration were used to make the laser compact and power scalable. The output was a rectangular annulus, which was further expanded to a square annulus and was adaptively corrected by an extra-cavity deformable mirror (DM). The DM was designed to be capable of correcting the square annular wavefront aberrations. In the experiment, the vertical beam quality was improved from 51.7 to 2.6 times diffraction limited after correction. To the best of our knowledge, this is the highest power and brightness based on a CW Nd:YAG oscillator.