•Biodegradable N-CD@LiFePO4 p-n junctions exhibited enhanced SDT performance.•Fe2+ catalyzed •OH production and Fe3+ oxidized consumption of overexpressed GSH.•LiFePO4 was slowly degraded into ...non-toxic species of Li+, Fe3+, and PO43-.•Ultrasmall N-CDs were released from the composite for renal elimination.•Complete tumor eradication was realized by N-CD@LiFePO4 under single US irradiation.
It is important yet challenging to develop a class of biocompatible semiconductor heterojunction sonosensitizers with enhanced charge carrier separation dynamics and tumor microenvironment (TME) regulating capability. Considering its p-type conductivity, Fe2+/Fe3+-based TME regulating capability, and biodegradability of an olivine iron phosphate, we presented a new sonosensitizer design by p-n junction engineering of partially oxidized LiFePO4 nanorods and renal-clearable n-type N-doped CDs (N-CDs) to achieve the effective spatial separation of the US-generated electron-hole pairs for enhanced sonodynamic therapy (SDT) of tumors. The constructed N-CD@LiFePO4 p-n junction sonosensitizer was found to exhibit high-efficiency 1O2 generation, Fe2+ catalyzed •OH production, and Fe3+-oxidized consumption of overexpressed GSH. The Fe2+ catalyzed H2O2 decomposition efficiency of N-CD@LiFePO4 was much higher than previously reported Fe3O4 nano-enzymes owing to the presence of (PO4)3- polyanions. Moreover, LiFePO4 was slowly degraded into non-toxic species of Li+, Fe3+, and PO43- while ultrasmall N-CDs were released from the composite for renal elimination, enabling the nanosonosensitizer to be harmlessly cleared out of the body after completion of SDT-based tumor eradication by single drug injection and single ultrasound (US) irradiation. The rationally designed p-n junction sonosensitizers could promote their SDT translation because of component biocompatibility, p-n junction configuration, and Fe2+/Fe3+ mediated TME regulation.
•Co3O4@TiO2-x were synthesized for Z-scheme HJ-enhanced SDT-nanocatalytic therapy.•HJs enhanced SDT properties and triple enzyme-mimic activities of Co3O4@TiO2-x.•Co2+ and Ti3+ ions catalyzed the ...Fenton-like reaction to generate more •OH.•Co3+ ions overcame GSH-mediated resistance to SDT and nanocatalytic therapy.•Complete tumor eradication was realized by Co3O4@TiO2-x under US irradiation.
Nanozymes have shown promising potential in cancer therapy owing to the advantages of low-cost, excellent stability, and high reproducibility. However, the inherent low catalytic activity of nanozymes and highly complex tumor microenvironment (TME) severely restricted the clinical applications of nanocatalytic therapy. Herein, we first reported a heterojunction (HJ)-enhanced nanocatalytic-sonodynamic therapy platform based on Co3O4@TiO2-x Z-scheme HJs by depositing Co3O4 nanoparticles (NPs) onto TiO2-x nanosheets (NSs). Co3O4@TiO2-x HJs not only exhibited excellent ultrasound (US)-triggered reactive oxygen species (ROS) generation ability, but also possessed triple enzyme-mimic activities (peroxidase-mimic, catalase-mimic, and GSH depletion activities) to realize the amplification of ROS levels and relieve tumor hypoxia. More importantly, the triple enzyme-mimic activities and sonodynamic properties of single-component Co3O4 or TiO2-x were greatly enhanced by the construction of Z-scheme HJs owing to the accelerate carrier transfer process and improved spatial separation dynamics of US-generated electron-hole pairs. The synergetic therapeutic effect of Co3O4@TiO2-x through HJ-enhanced nanocatalytic-sonodynamic therapy could achieve complete tumor eradication without recurrence. Our work will open up a promising approach to engineer semiconductor HJs with both sonodynamic and enzyme-mimic activities for enhanced nanocatalytic-sonodynamic combination therapy.
•A continuous flow reactor with granules was operated in different aeration modes.•Simultaneous N and P removal was achieved under 4 h aeration and 1 h non-aeration.•Appropriate intermittent aeration ...improved the settling ability of granules.•Archaeal and bacterial communities dynamics were explored by MiSeq pyrosequencing.•The SNDPR granular conceptual model in continuous flow system was established.
In this study, a continuous flow reactor with simultaneous nitrification, denitrification and phosphorus removal (SNDPR) granular sludge was operated in the continuous aeration (CA) and intermittent aeration (IA) modes to examine the effect of aeration on the performance of continuous-flow system. Then the experimental results showed that the IA1 mode (4 h aeration and 1 h non-aeration) could improve the simultaneous nitrogen and phosphorus removal and the settleability of granules in continuous flow system. Results of high-throughput pyrosequencing illustrated that the methanogens, AOA, ANAMMOX, DNB, denitrifying polyphosphate-accumulating organisms (DPAOs) were the important participant of simultaneous biological nutrients removal (SBNR), meanwhile, the IA1 mode could effectively inhibit the growth of filamentous microorganisms (Thiothrix and Acinetobacter). Finally, a conceptual model of the SNDPR granular microbial ecosystem under IA1 mode was proposed as a base for analyzing the mechanism of simultaneous nutrient removal in continuous flow system.
Neurodegenerative diseases are associated with heterogeneity in genetics, pathology, and clinical manifestation. Understanding this heterogeneity is particularly relevant for clinical prognosis and ...stratifying patients for disease modifying treatments. Recently, data-driven methods based on neuroimaging have been applied to investigate the subtyping of neurodegenerative disease, helping to disentangle this heterogeneity. We reviewed brain-based subtyping studies in aging and representative neurodegenerative diseases, including Alzheimer's disease, mild cognitive impairment, frontotemporal dementia, and Lewy body dementia, from January 2000 to November 2022. We summarized clustering methods, validation, robustness, reproducibility, and clinical relevance of 71 eligible studies in the present study. We found vast variations in approaches between studies, including ten neuroimaging modalities, 24 cluster algorithms, and 41 methods of cluster number determination. The clinical relevance of subtyping studies was evaluated by summarizing the analysis method of clinical measurements, showing a relatively low clinical utility in the current studies. Finally, we conclude that future studies of heterogeneity in neurodegenerative disease should focus on validation, comparison between subtyping approaches, and prioritise clinical utility.
•A breakable grain-based model based on FDEM is established for brittle heterogeneous rock.•Simulating the meso-scale mode I fracture characteristics of Beishan granite via SCB specimens.•Taking into ...account the length of the fracture process zone (FPZ) to investigate mode I fracture toughness.
The failure of brittle rock has a significant influence on engineering stability. The purpose of this study is to understand the progressive fracture mechanism of heterogeneous granite from a mesoscopic perspective. In the present work, the fracture process zone (FPZ) model is used to characterize the constitutive relationship of rock cracking in the combined finite-discrete element method (FDEM). Moreover, the breakable grain-based model (bGBM) is established to study the fracture behavior of granite via the semi-circular bending (SCB) tests. To rebuild the meso-structure of granite specimens, an algorithm that considers the mesoscopic grain geometry characteristics and grain contact mechanical properties is utilized. Then, three classic examples, namely, a uniaxial compressive test, a Brazilian splitting test and a semi-circular bending test, are investigated with the numerical model. A good agreement of the load–displacement curves and crack propagation paths can be found between the simulation and laboratory tests. The meso-heterogeneity of granite cause the macroscopic fracture surface of the slit tip to be nearly upright, with local roughness and zigzag. The slit length has a significant effect on the damage distribution range of the SCB specimen, and the peak load and mode I fracture toughness decreases with increasing slit length and supporting span. The accurate measurement of the mode I fracture toughness of SCB specimens needs to consider the FPZ, and the average increment is 39% and 41% under different slit length and supporting span conditions, respectively.
In this study, the Voronoi-based breakable block model (VBBM) based on the combined finite-discrete element method (FDEM) is used to investigate the failure mechanism of mine pillars and the ...rock-rockbolt interactions. The mechanical parameters of grout-rock and grout-bolt interfaces of a fully-grouted bolt are calibrated via numerical pull-out tests. Then, uniaxial compression tests are carried out on the reinforced pillars. The kinetic energy release rate (KERR) and crack aperture (CA) are used to evaluate the reinforcement effect. The results revealed that the VBBM can effectively characterize the damage failure mechanisms of spalling on the pillar surface and conjugate shear failure in the core zone of the pillar and reproduce the pre-peak nonlinear deformation and post-peak pseudo-ductile behaviors. The passive confining pressure generated by rockbolts is activated only when the rock mass produces sufficient deformation, and the constraints generated by different numbers of rockbolts can only affect the post-peak behavior of the pillar. There is a gradient feature in the internal deformation of the pillar from the shallow surface to the core. If the rockbolt density meets the strain demand, then rockbolts can delay the inward expansion of cracks by generating local constraints and can effectively fix the spalling rock blocks. With increasing support pressure, the CA and KERR exhibit a decreasing trend and strong power-exponential relationships with support pressure, indicating that there is a transition interval of support pressure and an optimal value for setting the rockbolt density.
•A novel numerical model (VBBM) is utilized to characterize the damage mechanisms of mine pillars.•The approach of combining the VBBM and the fully-grouted rockbolts is first used to explore the reinforcement effect.•The crack aperture and kinetic energy release rate are used to quantify the support effect.
Power supply and long distance cable are difficult in a field. Hence, a low power high-frequency capacitive soil water content sensor was developed. It consisted of an adjustable signal generating ...circuit, a signal attenuator, a true RMS detection circuit, a RC charge and discharge circuit, and two probe electrodes. The probe electrode was made up of PCB (Printed Circuit Board). In order to reduce entire energy consumption, the optimization design of sensor circuit was conducted. The results showed that the output voltage of the sensor had a positive linear correlation with soil volumetric moisture content, and the coefficient of determination R2 was 0.989. The stability and consistency of the soil moisture sensor met the needs of the long-term monitoring soil moisture content. PUBLICATION ABSTRACT
•TIO and SIO modes in SNDPR granular continuous-flow systems were evaluated.•The granules maintained better performance in TIO mode.•The PN and value of PN/PS were higher in SIO mode.•Filamentous ...Methanothrix and Thiothrix was related to the increase of EPS and SVI.•Functional archaeal and bacterial groups for nutrients removal were identified.
Continuous flow reactors with time intermittent operational (TIO) mode and spatial intermittent operational (SIO) mode were operated to evaluate the effects of operational modes on the removal performances, the characteristics of granules and the dynamics of microbial communities in simultaneous nitrification, denitrification and phosphorus removal (SNDPR) granular system. The results showed that the removal efficiency of TP, TN were 81.3%, 86.7% under TIO mode, and 70.6%, 77.4% under SIO mode, respectively. Meanwhile, the PN and value of PN/PS in SIO were higher than those in TIO. Besides, results of high-throughput pyrosequencing illustrated that the combination of filamentous archaea (Methanothrix) and filamentous bacteria (Thiothrix) had resulted in the increase of EPS and SVI under SIO mode. Finally, functional bacterial and archaeal species, involving HMA, AMA, AOA, DPAOs etc., were identified to reveal the effects of operational modes on the mechanism of nutrients removal in granular SNDPR continuous-flow system.
