Bottle Nanomotors Amplify Tumor Oxidative Stress for Enhanced Calcium Overload/Chemodynamic Therapy.

Developing multifunctional, stimuli-responsive nanomedicine is intriguing because it has the potential to effectively treat cancer. Yet, poor tumor penetration of nanodrugs results in limited antitumor efficacy. Herein, an oxygen-driven silicon-based nanomotor (Si-motor) loaded with MnO and CaO2 nanoparticles is developed, which can move in tumor microenvironment (TME) by the cascade reaction of CaO2 and MnO. Under acidic TME, CaO2 reacts with acid to release Ca2+ to induce mitochondrial damage and simultaneously produces O2 and H2O2, when the loaded MnO exerts Fenton-like activity to produce ·OH and O2 based on the produced H2O2. The generated O2 drives Si-motor forward, thus endowing active delivery capability of the formed motors in TME. Meanwhile, MnO with glutathione (GSH) depletion ability further prevents reactive oxygen species (ROS) from being destroyed. Such TME actuated Si-motor with enhanced cellular uptake and deep penetration provides amplification of synergistic oxidative stresscaused by intracellular Ca2 + overloading, GSH depletion induced by Mn2+, and Mn2+ mediated chemodynamic treatment (CDT), leading to excellent tumor cell death. The created nanomotor may offer an effective platform for active synergistic cancer treatment.

Light-Driven Biomimetic Nanomotors for Enhanced Photothermal Therapy.

Nanotechnology-based strategy has recently drawn extensive attention for the therapy of malignant tumors due to its distinct strengths in cancer diagnosis and treatment. However, the limited intratumoral permeability of nanoparticles is a major hurdle to achieving the desired effect of cancer treatment. Due to their superior cargo towing and reliable penetrating property, micro-/nanomotors (MNMs) are considered as one of the most potential candidates for the coming generation of drug delivery platforms. Here, near-infrared (NIR)-actuated biomimetic nanomotors (4T1-JPGSs-IND) are fabricated successfully and we demonstrate that 4T1-JPGSs-IND selectively accumulate in homologous tumor regions due to the effective homing ability. Upon laser irradiation, hyperthermia generated by 4T1-JPGSs-IND leads to self-thermophoretic motion and photothermal therapy (PTT) to ablate tumors with a deep depth, thereby improving the photothermal therapeutic effect for cancer management. The developed nanomotor system with multifunctionalities exhibits promising potential in biomedical applications to fight against various diseases.

Application of Microscopic Highly Hydrophilic Silica-Based Nanocomposites with High Surface Exposure in the Efficient Identification of Intact N-Glycopeptides.

Glycosylation of proteins regulates the life activities of organisms, while abnormalities of glycosylation sites and glycan structures occur in various serious diseases such as cancer. A separation and enrichment procedure is necessary to realize the analysis of the glycoproteins/peptides by mass spectrometry, for which the surface hydrophilicity of the material is an important factor for the separation and enrichment performance. In the present work, under the premise of an obvious increase of the surface silicon exposure (79.6%), the amount of surface polar silanol is remarkably generated accompanying the introduction of the active amino groups on the surface of silica. The microscopic hydrophilicity, which is determined with water physical-adsorption measurements and can directly reflect the interaction of water molecules and the intrinsic surface of the material, maximally increases by 44%. This microscopically highly hydrophilic material shows excellent enrichment ability for glycopeptides, such as extremely low detection limits (0.01 fmol µL-1), remarkable selectivity (1:8000), and size exclusion effects (1:8000). A total of 677 quantifiable intact N-glycopeptides were identified from the serum of patients with cervical cancer, and the glycosylation site and glycan structure were analyzed in depth, indicating that this novel material can show a broad practical application in cervical cancer diagnosis.

Control the Neural Stem Cell Fate with Biohybrid Piezoelectrical Magnetite Micromotors.

Inducing neural stem cells to differentiate and replace degenerated functional neurons represents the most promising approach for neural degenerative diseases including Parkinson's disease, Alzheimer's disease, etc. While diverse strategies have been proposed in recent years, most of these are hindered due to uncontrollable cell fate and device invasiveness. Here, we report a minimally invasive micromotor platform with biodegradable helical Spirulina plantensis (S. platensis) as the framework and superparamagnetic Fe3O4 nanoparticles/piezoelectric BaTiO3 nanoparticles as the built-in function units. With a low-strength rotational magnetic field, this integrated micromotor system can perform precise navigation in biofluid and achieve single-neural stem cell targeting. Remarkably, by tuning ultrasound intensity, thus the local electrical output by the motor, directed differentiation of the neural stem cell into astrocytes, functional neurons (dopamine neurons, cholinergic neurons), and oligodendrocytes, can be achieved. This micromotor platform can serve as a highly controllable wireless tool for bioelectronics and neuronal regenerative therapy.

Apoptotic Tumor DNA Activated Nanomotor Chemotaxis.

Inspired by the tactic organisms in Nature that can self-direct their movement following environmental stimulus gradient, we proposed a DNase functionalized Janus nanoparticle (JNP) nanomotor system for the first time, which can be powered by ultralow nM to µM levels of DNA. The system exhibited interesting chemotactic behavior toward a DNA richer area, which is physiologically related with many diseases including tumors. In the presence of the subtle DNA gradient generated by apoptotic tumor cells, the cargo loaded nanomotors were able to sense the DNA signal released by the cells and demonstrate directional motion toward tumor cells. For our system, the subtle DNA gradient by a small amount (10 µL) of tumor cells is sufficient to induce the chemotaxis behavior of self-navigating and self-targeting ability of our nanomotor system, which promises to shed new light for tumor diagnosis and therapy.

Experimental Research on Shear Failure Monitoring of Composite Rocks Using Piezoelectric Active Sensing Approach.

Underground space engineering structures are generally subject to extensive damages and significant deformation. Given that composite rocks are prone to shear failure, which cannot be accurately monitored, the piezoelectric active sensing method and wavelet packet analysis method were employed to conduct a shear failure monitoring test on composite rocks in this study. For the experiment, specimens were prepared for the simulation of the composite rocks using cement. Two pairs of piezoelectric smart aggregates (SAs) were embedded in the composite specimens. When the specimens were tested using the direct shear apparatus, an active sensing-based monitoring test was conducted using the embedded SAs. Moreover, a wavelet packet analysis was conducted to compute the energy of the monitoring signal; thus allowing for the determination of the shear damage index of the composite specimens and the quantitative characterization of the shear failure process. The results indicated that upon the shear failure of the composite specimens, the amplitudes and peak values of the monitoring signals decreased significantly, and the shear failure and damage indices of the composite specimens increased abruptly and approached a value of 1. The feasibility and reliability of the piezoelectric active sensing method, with respect to the monitoring of the shear failure of composite rocks, was therefore experimentally demonstrated in this study.

Fabrication of Self-Propelled Micro- and Nanomotors Based on Janus Structures.

Delicate molecular and biological motors are tiny machines capable of achieving numerous vital tasks in biological processes. To gain a deeper understanding of their mechanism of motion, researchers from multiple backgrounds have designed and fabricated artificial micro- and nanomotors. These nano-/microscale motors can self-propel in solution by exploiting different sources of energy; thus showing tremendous potential in widespread applications. As one of the most common motor systems, Janus motors possess unique asymmetric structures and integrate different functional materials onto two sides. This review mainly focuses on the fabrication of different types of micro- and nanomotors based on Janus structures. Furthermore, some challenges still exist in the implementation of Janus motors in the biomedical field. With such common goals in mind, it is expected that the elaborate and multifunctional design of Janus motors will overcome their challenges in the near future.

Inhibition of Phosphodiesterase 4 by FCPR03 Alleviates Lipopolysaccharide-Induced Depressive-Like Behaviors in Mice: Involvement of p38 and JNK Signaling Pathways.

Inflammatory responses induced by peripheral administration of lipopolysaccharide (LPS) triggers depressive-like behavioral syndrome in rodents. Inhibition of phosphodiesterase 4 (PDE4) produces a robust anti-inflammatory effect in inflammatory cells. Unfortunately, archetypal PDE4 inhibitors cause intolerable gastrointestinal side-effects, such as vomiting and nausea. N-isopropyl-3-(cyclopropylmethoxy)-4-difluoromethoxy benzamide (FCPR03) is a novel, selective PDE4 inhibitor with little, or no, emetic potency. Our previous studies show that FCPR03 is effective in attenuating neuroinflammation in mice treated with LPS. However, whether FCPR03 could exert antidepressant-like effect induced by LPS is largely unknown. In the present study, mice injected intraperitoneally (i.p.) with LPS was established as an in vivo animal model of depression. The antidepressant-like activities of FCPR03 were evaluated using a tail suspension test, forced swimming test, and sucrose preference test. We demonstrated that administration of FCPR03 (1 mg/kg) produced antidepressant-like effects in mice challenged by LPS, as evidenced by decreases in the duration of immobility in the forced swim and tail suspension tests, while no significant changes in locomotor activity were observed. FCPR03 also increased sucrose preference in mice treated with LPS. In addition, treatment with FCPR03 abolished the downregulation of brain-derived neurotrophic factor induced by LPS and decreased the level of corticosterone in plasma. Meanwhile, periphery immune challenge by LPS induced enhanced phosphorylation of p38-mitogen activated protein kinase (p38) and c-Jun N-terminal kinase (JNK) in both the cerebral cortex and hippocampus in mice. Interestingly, treatment with FCPR03 significantly blocked the role of LPS and reduced the levels of phosphorylated p38 and JNK. Collectively, these results indicate that FCPR03 shows antidepressant-like effects in mice challenged by LPS, and the p38/JNK signaling pathway is possibly involved in this process. Our findings suggest that FCPR03 is a potential compound for the prevention or treatment of depression.

A NIR-driven green affording-oxygen microrobot for targeted photodynamic therapy of tumors.

Photodynamic therapy (PDT) is a light-activated local treatment modality that has promising potential in cancer therapy. However, ineffective delivery of photosensitizers and hypoxia in the tumor microenvironment severely restrict the therapeutic efficacy of PDT. Herein, phototactic Chlorella (C) is utilized to carry photosensitizer-encapsulated nanoparticles to develop a near-infrared (NIR) driven green affording-oxygen microrobot system (CurNPs-C) for enhanced PDT. Photosensitizer (curcumin, Cur) loaded nanoparticles are first synthesized and then covalently attached to C through amide bonds. An in vitro study demonstrates that the developed CurNPs-C exhibits continuous oxygen generation and desirable phototaxis under NIR treatment. After intravenous injection, the initial 660 nm laser irradiation successfully induces the active migration of CurNPs-C to tumor sites for higher accumulation. Upon the second 660 nm laser treatment, CurNPs-C produces abundant oxygen, which in turn induces the natural product Cur to generate more reactive oxygen species (ROS) that significantly inhibit the growth of tumors in 4T1 tumor-bearing mice. This contribution showcases the ability of a light-driven green affording-oxygen microrobot to exhibit targeting capacity and O2 generation for enhancing photodynamic therapy.

Scientometric analysis on the review research evolution of tailings dam failure disasters.

As the most severe damage form of tailings ponds, dam failure causes a serious threat and damage to the surrounding lives and environment. Therefore, based on the systematic collection and consultation of relevant data at home and abroad, the literature source analysis on tailings dam failure disasters is conducted using the CiteSpace scientometric tool. The research on tailings dam failure disasters can be classified into two stages: the preliminary germination stage and rapid development stage. Based on the scientometric knowledge map, the research hotspots of tailings dam failure disasters are analyzed and summarized as three main research directions: environmental impact, risk assessment, and mechanical behavior. With the maturity of the research on ecological problems caused by tailings leakage, ecological restoration has also gradually become a hot research topic. Through the analysis of keyword bursts and co-cited bursts, the research frontier of tailings dam break disaster is explored. "Risk management," "real-time monitoring," and "tailings characteristic" represent the current research frontier. Among them, risk management is burst for the longest time and is expected to be a very important research direction in the future. Finally, a tailings pond risk management and control suggestion is proposed with risk management as the core, emphasizing risk monitor, and combined with dynamic risk control, which provides a foundation for the construction of tailings dam safety management and dynamic monitoring systems.

Study on mechanical properties and damage characteristics of cemented waste rock-tailing backfill.

Tailing and waste rock-cemented filling is an effective way to solve the problem solid waste in mines. In this paper, the effects of waste rock content and cement-sand ratio on the properties of tailing-waste rock-cemented filling materials and cemented backfill were analyzed based on the single-factor multi-level experimental design method. The results show that with the increase of waste rock content, the fluidity of the filling slurry increases first and then decreases, the bleeding rate increased gradually, and the compressive strength of the backfill increases first and then decreases. When the waste rock content is 60% and the cement-sand ratio is 1:4, the cemented backfill has higher compressive strength. With the increase of waste rock content, the interface failure area between waste rock particles and cementitious matrix under loading gradually increases, the crack extension is more complex, and the acoustic emission (AE) ringing count is higher. Microstructural analysis showed that the main hydration products in the cemented backfill were calcium silicate hydrated (C-S-H) gels, ettringite (AFt), and calcium hydroxide (Ca(OH)2). Because there is more content of hydration products, the microstructure of the cemented backfill was denser and the compressive strength was higher. Based on the results of uniaxial compression tests, the damage constitutive model of cemented backfill with different waste rock contents and cement-sand ratios was established, which could provide guidance for the design and safety production of phosphate rock filling engineering.

Leaching toxicity and deformation failure characteristics of phosphogypsum-based cemented paste backfill under chemical solution erosion.

In order to explore the potential environmental and safety risks of phosphogypsum-based cemented paste backfill (PCPB) in mines, aiming at the actual problems of different acidity and alkalinity of the groundwater environment where PCPB is located, the chemical solution erosion test, element concentration determination test, uniaxial compressive strength (UCS) test, and microscopic analysis test of PCPB were carried out. The effects of three different chemical solutions, HCl solution, NaOH solution, and pure water on the leaching toxicity and deformation failure characteristics of PCPB were analyzed. The kinetic equations of pH value of PCPB in the HCl and NaOH solutions, the leaching models of total P and fluoride, and the UCS erosion model of PCPB were established. The research shows that the pH value of PCPB is weak alkaline or alkalinity, when it reaches dynamic equilibrium in different chemical solutions. The leaching concentration of total P is higher than the Class III standard of surface water; the leaching concentration of fluoride is higher than the Class III standard of surface water, the Class III standard of groundwater, and the Class I standard of sewage. In the early stage of chemical solution erosion, scanning electron microscope (SEM) images show that the hydration product C-S-H gel and Aft are intertwined and firmly combined. The research results have important engineering practice and application value in mine environmental governance and safety management.

Influence of partial cement substitution by ground blast furnace slag on the mechanical properties of phosphogypsum cemented backfill.

Phosphogypsum (PG) stockpiles occupied a large amount of land resources, and serious environmental pollution problems have attracted the attention of countries around the world. Cemented backfill can reduce the environmental problems caused by tailings stockpiles and is an important development trend in green mine construction. To investigate the effect of binder type on the performance of PG cemented backfill, this paper used ground granulated blast furnace slag (GGBFS) to substitute part of Portland cement (PC) as binder and studied the effect of different ratios of binder on the uniaxial compressive strength (UCS), surface crack extension, acoustic emission (AE) characteristics, and microstructure of PG cemented backfill. The results show that substituting part of PC with GGBFS is beneficial to improve the mechanical properties of PG cemented backfill. When PC was substituted by 50% of GGBFS, the 28d UCS of the backfill was increased from 1.535 to 4.539 MPa. Furthermore, the UCS of the backfill gradually increased as the GGBFS substitution level increased, and more AE signals could be monitored during uniaxial compression. Compared with PC, the sulfate in PG participates in the hydration reaction of GGBFS, more hydrated calcium-aluminum-silicate-hydrate (C-A-S-H) gels and ettringite (AFt) are formed, and the microstructure of the backfill is denser, and the required strength can be obtained with less binder. Thus, substituting part PC with GGBFS as a binder can provide an economical and environmentally friendly alternative for the consumption and reuse of large quantities of PG.

Dip effect of asymmetric deformation characteristics for stope roof-pillar system.

In underground mining, the dip angle is one of the widely recognized factors that cause the asymmetric deformation of the goaf/stope roof, but characterizing the degree of asymmetric roof deformation is still a challenge. The goal of this research is to try to solve this problem with a theoretical model and numerical method. In an inclined ore seam, the mining load produces both normal and tangential effects on the inclined roof. A theoretical model was developed employing thin plate theory for enabling describe the asymmetric deformation of the roof caused by inclination. The proposed model describes not only the bending deformation state of the roof but also the deformation characteristics. Subsequently, the law of asymmetric deformation of roofs with varying inclinations was presented by numerical method. Under the same conditions, the numerical results of the asymmetric deformation of the roof are consistent with the theoretical results. Finally, the degree of asymmetrical deformation was characterized and quantified by the distance between the maximum subsidence point and the center of the roof. There exist three modes of asymmetric deformation, which are controlled by both dip angle and in-situ stress ratio. The results show that the shear load caused by dip angle is the root cause of asymmetric deformation of the roof. This study provides a theoretical basis for the asymmetric deformation control of the inclined roof.

Mechanical properties and damage constitutive model of phosphogypsum-based cemented backfill under hydrochemical action.

In order to analyze the early mechanical properties and damage characteristics of phosphogypsum-based cemented backfill (PCB) under hydrochemical action, hydrochemical erosion and uniaxial compression strength (UCS) tests were carried out with HCl solution, NaOH solution, and water respectively. The damage degree is defined by taking the effective bearing area of the soluble cements of PCB under hydrochemistry action as the chemical damage variable, and the modified damage parameter α, which reflects the damage development characteristics, is introduced to construct the damage constitutive model of PCB considering chemical damage and load damage, and the theoretical model is verified with the experimental results. The results show that the damage constitutive model curves of PCB under different hydrochemical action are in good agreement with the experimental results, which verifies the correctness of the theoretical model. When the modified damage parameter α decreases from 1.0 to 0.8, the residual load-bearing capacity of PCB gradually increases, with the damage values of PCB samples in HCl solution and water gradually increasing before the peak and decreasing after the peak, while the damage values of PCB samples in NaOH solution show an overall increasing trend before and after the peak. The slope of the post peak curve of PCB decreases with increasing model parameter n. The results of the study can provide theoretical support and practical guidance for the strength design, long-term erosion deformation, and prediction of PCB in hydrochemical environment.

Magnetically Actuated Biodegradable Nanorobots for Active Immunotherapy.

An efficient and cost-effective therapeutic vaccine is highly desirable for the prevention and treatment of cancer, which helps to strengthen the immune system and activate the T cell immune response. However, initiating such an adaptive immune response efficiently remains challenging, especially the deficient antigen presentation by dendritic cells (DCs) in the immunosuppressive tumor microenvironment. Herein, an efficient and dynamic antigen delivery system based on the magnetically actuated OVA-CaCO3 -SPIO robots (OCS-robots) is rationally designed for active immunotherapy. Taking advantage of the unique dynamic features, the developed OCS-robots achieve controllable motion capability under the rotating magnetic field. Specifically, with the active motion, the acid-responsiveness of OCS-robots is beneficial for the tumor acidity attenuating and lysosome escape as well as the subsequent antigen cross-presentation of DCs. Furthermore, the dynamic OCS-robots boost the crosstalk between the DCs and antigens, which displays prominent tumor immunotherapy effect on melanoma through cytotoxic T lymphocytes (CTLs). Such a strategy of dynamic vaccine delivery system enables the active activation of immune system based on the magnetically actuated OCS-robots, which presents a plausible paradigm for incredibly efficient cancer immunotherapy by designing multifunctional and novel robot platforms in the future.

Hyperthermia-triggered biomimetic bubble nanomachines.

Nanoparticle-based drug delivery systems have gained much attention in the treatment of various malignant tumors during the past decades. However, limited tumor penetration of nanodrugs remains a significant hurdle for effective tumor therapy due to the existing biological barriers of tumoral microenvironment. Inspired by bubble machines, here we report the successful fabrication of biomimetic nanodevices capable of in-situ secreting cell-membrane-derived nanovesicles with smaller sizes under near infrared (NIR) laser irradiation for synergistic photothermal/photodynamic therapy. Porous Au nanocages (AuNC) are loaded with phase transitable perfluorohexane (PFO) and hemoglobin (Hb), followed by oxygen pre-saturation and indocyanine green (ICG) anchored 4T1 tumor cell membrane camouflage. Upon slight laser treatment, the loaded PFO undergoes phase transition due to surface plasmon resonance effect produced by AuNC framework, thus inducing the budding of outer cell membrane coating into small-scale nanovesicles based on the pore size of AuNC. Therefore, the hyperthermia-triggered generation of nanovesicles with smaller size, sufficient oxygen supply and anchored ICG results in enhanced tumor penetration for further self-sufficient oxygen-augmented photodynamic therapy and photothermal therapy. The as-developed biomimetic bubble nanomachines with temperature responsiveness show great promise as a potential nanoplatform for cancer treatment.

Real-Time Micromotor Probe for Immune Neutrophil Activation State.

Neutrophil activation is a hallmark of the immune response. Approaches to identify neutrophil activation in real time are necessary but are still lacking. In this study, magnetic Spirulina micromotors are used as label-free probes that exhibit differences in motility under different neutrophil activation states. This is correlated with different secretions into the extracellular environment by activated/non-activated cells and local environmental viscoelasticity. The micromotor platform can bypass non-activated immune cells while being stopped by activated cells. Thus, the micromotors can serve as label-free biomechanical probes of the immune cell state. They can detect the activation state of target immune cells in real time and with single-cell precision, which provides new ideas for the diagnosis and treatment of diseases while deepening understanding of the biomechanics of activated immune cells.

Arthritic Microenvironment Actuated Nanomotors for Active Rheumatoid Arthritis Therapy.

Increasing O2 demand and excessive ROS production are the main features of arthritic microenvironment in rheumatoid arthritis (RA) joints and further play pivotal roles in inflammation exacerbation. In this work, a system of in situ regulation of arthritic microenvironment based on nanomotor strategy is proposed for active RA therapy. The synthesized MnO2 -motors enable catalytic regulation of RA microenvironment by consuming the overproduced H2 O2 and generating O2 synergistically. The generated O2 under H2 O2 -rich conditions functions as inflammation detector, propellant for enhanced diffusion, as well as ameliorator for the hypoxic synovial microenvironment. Owing to O2 generation and inflammation scavenging, the MnO2 -motors block the re-polarization of pro-inflammatory macrophages, which results in significantly decreased secretion of multiple pro-inflammatory cytokines both in vitro and in vivo. In addition, intra-articular administration of MnO2 -motors to collagen-induced arthritis rats (CIA rats) effectively alleviates hypoxia, synovial inflammation, bone erosion, and cartilage degradation in joints. Therefore, the proposed arthritic regulation strategy shows great potential to seamlessly integrate basic research of RA with clinical translation.