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To ensure the safety of excavations such as large section tunnels of the Guangxi Liubin Highway Tunnel Project, we implemented a simulation analysis of 3D tunnel models based on finite software for different construction methods. Different from the traditional simulation, this paper uses various construction methods to compare, study, and analyze the advantages and disadvantages of different excavation methods by combining them with the excavation. The feasibility of different construction methods was analyzed by studying the mechanical characteristics and settlement changes using the Cross Diaphragm (CRD), Center Diaphragm (CD), and full-section methods while building a large section tunnel. The arch perimeter deformation and surface settlement during the initial support and secondary lining proved that the CRD excavation method is the most favorable and causes the least damage to the stability of the surrounding rock. For the analysis of surface subsidence, the “V”-shaped surface subsidence curve excavated by the CRD method is the closest to the subsidence curve. However, we used the adjusted peak formula to fit the prediction formula for the surface settlement curve of the deep-buried two-lane tunnel with a large cross-section applicable to this project, which will provide an important reference for similar projects.

The in situ lactate oxidase (LOx) catalysis is highly efficient in reducing oxygen to H2O2 due to the abundant lactate substrate in the hypoxia tumor microenvironment. Dynamic therapy, including chemodynamic therapy (CDT), photodynamic therapy (PDT), and enzyme dynamic therapy (EDT), could generate reactive oxygen species (ROS) including ·OH and 1O2 through the disproportionate or cascade biocatalytic reaction of H2O2 in the tumor region. Here, we demonstrate a ROS-based tumor therapy by integrating LOx and the antiglycolytic drug Mito-LND into Fe3O4/g-C3N4 nanoparticles coated with CaCO3 (denoted as FGLMC). The LOx can catalyze endogenous lactate to produce H2O2, which decomposes cascades into ·OH and 1O2 through Fenton reaction-induced CDT and photo-triggered PDT. Meanwhile, the released Mito-LND contributes to metabolic therapy by cutting off the source of lactate and increasing ROS generation in mitochondria for further improvement in CDT and PDT. The results showed that the FGLMC nanoplatform can multifacetedly elevate ROS generation and cause fatal damage to cancer cells, leading to effective cancer suppression. This multidirectional ROS regulation strategy has therapeutic potential for different types of tumors.

Photothermal therapy (PTT) combined with second near-infrared (NIR-II) fluorescence imaging (FI) has received increasing attention owing to its capacity for precise diagnosis and real-time monitoring of the therapeutic effects. It is of great clinical value to study organic small molecular fluorophores with both PTT and NIR-II FI functions. In this work, we report a skillfully fluorescent lipid nanosystem, the RR9 (RGDRRRRRRRRRC) peptide-coated anionic liposome loaded with organic NIR-II fluorophore IR-1061 and chemotherapeutic drug carboplatin, which is named RRIALP-C4. According to the structural interaction between IR-1061 and phospholipid bilayer demonstrated by molecular dynamics simulations, IR-1061 is rationally designed to possess the H-aggregated state versus the free state, thus rendering RRIALP-C4 with the activated dual-channel integrated function of intravital NIR-II FI and NIR-I PTT. Functionalization of RRIALP-C4 with RR9 peptide endows the specifically targeting capacity for αvβ3-overexpressed tumor cells and, more importantly, allows IR-1061 to transfer the H-aggregated state from liposomes to the tumor cell membrane through enhanced membrane fusion, thereby maintaining its PTT effect in tumor tissues. In vivo experiments demonstrate that RRIALP-C4 can effectively visualize tumor tissues and systemic blood vessels with a high sign-to-background ratio (SBR) to realize the synergistic treatment of thermochemotherapy by PTT synergistically with temperature-sensitive drug release. Therefore, the strategy of enhanced PTT through H-aggregation of NIR-II fluorophore in the tumor cell membrane has great potential for developing lipid nanosystems with integrated diagnosis and treatment function.

Multiple compression tests on rock-like samples of pre-existing cracks with different geometries were conducted to investigate the strength properties and crack propagation behavior considering multi-crack interactions. The progressive failure process of the specimens was segmented into four categories and seven coalescence modes were identified due to different crack propagation mechanisms. Ultimately, a mechanical model of the multi-crack rock mass was proposed to investigate the gradual fracture and damage evolution traits of the multi-crack rock on the basis of exploring the law of the compression-shear wing crack initiation and propagation. A comparison between theory and experimental results indicated that the peak strength of the specimens with multiple fractures decreased initially and subsequently increased with the increase in the fissure inclination angles; the peak strength of specimens decreased with the increase in the density of fissure distribution.

Hydrogen sulfide (H2S) as an important gaseous signaling molecule is closely related to numerous biological processes in living systems. To further study the physiological and pathological roles of H2S, convenient and efficient detection techniques for endogenous H2S in vivo are still in urgent demand. In this study, an electrochromic chromophore, dicationic 1,1,4,4-tetra-aryl butadiene (EM1), was innovatively introduced into upconversion nanoparticles (UCNPs) and a nanoprobe, PAAO-UCNPs-EM1, was constructed for the detection of H2S. This nanosystem was made of core-shell upconversion nanoparticles (NaYF4:Yb,Tm@NaYF4:Yb,Er), EM1, and polyacrylic acid (PAA)-octylamine. The EM1 with strong absorption ranging from 500 to 850 nm could serve as an energy acceptor to quench the upconversion luminescence of UCNPs through the Forster resonance energy transfer (FRET) process. In the presence of H2S, the EM1 in the nanoprobe was reduced to a colorless diene (EM2), resulting in the linear enhancement of luminescence emissions at 660 nm and 800 nm under the excitation of 980 nm light because the FRET was switched off. The nanoprobe PAAO-UCNPs-EM1PAAO-UCNPs-EM1 exhibited fast response and high sensitivity to H2S with a LoD of 1.21 × 10-7 M. Moreover, it was successfully employed in detecting the endogenous and exogenous H2S in living cells with high selectivity and low cytotoxicity. Also, this nanoprobe could distinguish normal and tumor cells by an upconversion luminescence imaging of endogenous H2S. Furthermore, the nanoprobe could significantly monitor H2S in a tumor-bearing nude mouse model. Therefore, we anticipate that this novel nanoprobe assembled with an electrochromic chromophore for responding to H2S and for bioimaging this molecule would have a promising prospect in biological and clinical investigations.

Lung metastasis is the principal reason for the majority of deaths from breast cancer. The nonsteroidal anti-inflammatory drug aspirin can prevent lung metastasis in breast tumors via inhibiting heparanase. However, the lack of specific targets and limited accumulation at the site of the tumor have thus far hindered the use of aspirin in oncotherapy. In this study, we developed the nanoplatform FA-BSA@DA and loaded it with the versatile aspirin prodrug DA to visualize and inhibit breast cancer metastasis via targeting heparanase. This nanosystem can be effectively targeted to folic acid (FA)-positive tumor cells, and would then subsequently release a high dose of DA, whose ester bond is specifically ruptured by H2O2 in the tumor microenvironment to afford the therapeutic drug aspirin and near-infrared (NIR) fluorescent reporter DCM. The released aspirin can effectively prevent breast cancer lung metastasis through the inhibition of heparanase activity, and the NIR fluorescent signals emitted from DCM can be used to monitor and evaluate the metastasis levels of breast cancer. Our results showed that the expression of heparanase was significantly decreased, and lung metastasis from breast cancer was effectively monitored and inhibited after treatment with FA-BSA@DA. Furthermore, the collaborative therapy nanoplatform FA-BSA@DA/DOX exhibited strong therapeutic effects in the treatment of breast cancer in vitro and in vivo via the introduction of doxorubicin (DOX) to the system, which resulted in an even stronger result due to its synergistic effects with aspirin. This heparanase-reliant strategy has profound significance for the extended development of nanoplatforms based on versatile aspirin prodrugs, which may offer a solution to clinically prevent breast cancer recurrence and lung metastasis.