An ATPase-Mimicking MXene nanozyme pharmacologically breaks the ironclad defense system for ferroptosis cancer therapy.

Anticancer nanomedicines used for ferroptosis therapy generally rely on the direct delivery of Fenton catalysts to drive lipid peroxidation in cancer cells. However, the therapeutic efficacy is limited by the ferroptosis resistance caused by the intracellular anti-ferroptotic signals. Herein, we report the intrinsic ATPase-mimicking activity of a vanadium carbide MXene nanozyme (PVCMs) to pharmacologically modulate the nuclear factor erythroid 2-related factor 2 (Nrf2) program, which is the master anti-ferroptotic mediator in the ironclad defense system in triple-negative breast cancer (TNBC) cells. The PVCMs perform high ATPase-like activity that can effectively and selectively catalyze the dephosphorylation of ATP to generate ADP. Through a cascade mechanism initiated by falling energy status, PVCMs can powerfully hinder the Nrf2 program to selectively drive ferroptosis in TNBC cells in response to PVCMs-induced glutathione depletion. This study provides a paradigm for the use of pharmacologically active nanozymes to moderate specific cellular signals and elicit desirable pharmacological activities for therapeutic applications.

The Effects of Immersion and Visuo-Tactile Stimulation on Motor Imagery in Stroke Patients are Related to the Sense of Ownership.

Visual guided motor imagery (MI) is commonly used in stroke rehabilitation, eliciting event-related desynchronization (ERD) in EEG. Previous studies found that immersion level and visuo-tactile stimulation could modulate ERD during visual guided MI, and both of two factors could also improve sense of ownership (SOO) over target limb (or body). Additionally, the relationship was also reported between the performance of MI and SOO. This study aims to investigate whether immersion and visuo-tactile stimulation affect visual guided MI through the SOO over virtual body in stroke patients. Nineteen stroke patients were recruited. The experiment included two phases (i.e., SOO induction and visual guided MI with SOO) that was manipulated across four conditions in a within-subject design: 2×2 , i.e., immersion (VR, 2D monitor display) × multisensory stimulation (visuo-tactile stimulation, observation without tactile stimulation). Results found peaks ERD amplitude during MI were significantly higher in stronger SOO conditions than weaker SOO conditions. Interestingly, the ERD during visual guided MI under the condition of vision only in VR and visuo-tactile stimulation in 2D monitor are similar, which indicates that SOO may be an important factor behind this phenomenon (due to the similar SOO between these two conditions). A moderate correlation was also found between SOO scores and peaks ERD amplitude during MI. This study discussed the possible factor underlying the effects of immersion and multisensory stimulation on visual guided MI in post-stroke patients, identifying the effect of SOO in this process, and could be referred in future studies for coming up with better MI paradigms for stroke rehabilitation.

Event-Related EEG Desynchronization Reveals Enhanced Motor Imagery From the Third Person Perspective by Manipulating Sense of Body Ownership With Virtual Reality for Stroke Patients.

Virtual reality (VR)-based rehabilitation training holds great potential for post-stroke motor recovery. Existing VR-based motor imagery (MI) paradigms mostly focus on the first-person perspective, and the benefit of the third-person perspective (3PP) remains to be further exploited. The 3PP is advantageous for movements involving the back or those with a large range because of its field coverage. Some movements are easier to imagine from the 3PP. However, the 3PP training efficiency may be unsatisfactory, which may be attributed to the difficulty encountered when generating a strong sense of ownership (SOO). In this work, we attempt to enhance a visual-guided 3PP MI in stroke patients by eliciting the SOO over a virtual avatar with VR. We propose to achieve this by inducing the so-called out-of-body experience (OBE), which is a full-body illusion (FBI) that people misperceive a 3PP virtual body as his/her own (i.e., generating the SOO to the virtual body). Electroencephalography signals of 13 stroke patients are recorded while MI of the affected upper limb is being performed. The proposed paradigm is evaluated by comparing event-related desynchronization (ERD) with a control paradigm without FBI induction. The results show that the proposed paradigm leads to a significantly larger ERD during MI, indicating a bilateral activation pattern consistent with that in previous studies. In conclusion, 3PP MI can be enhanced in stroke patients by eliciting the SOO through induction of the "OBE" FBI. This study offers more possibilities for virtual rehabilitation in stroke patients and can further facilitate VR application in rehabilitation.

Transforming Intratumor Bacteria into Immunopotentiators to Reverse Cold Tumors for Enhanced Immuno-chemodynamic Therapy of Triple-Negative Breast Cancer.

Immunotherapy of triple-negative breast cancer (TNBC) has an unsatisfactory therapeutic outcome due to an immunologically "cold" microenvironment. Fusobacterium nucleatum (F. nucleatum) was found to be colonized in triple-negative breast tumors and was responsible for the immunosuppressive tumor microenvironment and tumor metastasis. Herein, we constructed a bacteria-derived outer membrane vesicle (OMV)-coated nanoplatform that precisely targeted tumor tissues for dual killing of F. nucleatum and cancer cells, thus transforming intratumor bacteria into immunopotentiators in immunotherapy of TNBC. The as-prepared nanoparticles efficiently induced immunogenic cell death through a Fenton-like reaction, resulting in enhanced immunogenicity. Meanwhile, intratumoral F. nucleatum was killed by metronidazole, resulting in the release of pathogen-associated molecular patterns (PAMPs). PAMPs cooperated with OMVs further facilitated the maturation of dendritic cells and subsequent T-cell infiltration. As a result, the "kill two birds with one stone" strategy warmed up the cold tumor environment, maximized the antitumor immune response, and achieved efficient therapy of TNBC as well as metastasis prevention. Overall, this strategy based on a microecology distinction in tumor and normal tissue as well as microbiome-induced reversal of cold tumors provides new insight into the precise and efficient immune therapy of TNBC.

Personalized intermittent pneumatic calf compression frequency for augmenting foot blood perfusion: The optimized effect and a personalized mode predicting method.

Intermittent pneumatic compression (IPC) therapy has been adopted in prevention and treatment of ischemic-related peripheral vascular diseases. The aim of this study is to provide an approach to personalize the compression strategy of IPC therapy for maximizing foot skin blood flow. In this study, we presented a method to predict the optimized compression mode (OCM) for each subject based on biomechanical features extracted from experimental data tested with multiple IPC modes. First, to demonstrate the blood flow enhancing effect by applying the personalized OCM, four IPC modes of different frequency settings were tested on a total of 24 subjects. The frequency settings were adjusted by deflating-waiting time, which was defined as the total time length from the start of cuff deflation to the start of next compression. The foot skin blood perfusion and IPC air cuff pressure were monitored during the experiments. The personalized OCM was defined as the certain IPC mode that has the highest blood perfusion augmentation (BPA). Compared with the rest stage blood perfusion, the personalized OCM settings resulted in >50% of augmentation for 75% of healthy subjects (maximum augmentation at 244%) and >20% augmentation for 75% of patients with diabetes (maximum augmentation at 180%). Second, for predicting the OCM, we establish a random forest model based on the features extracted from the experimental data. The binary classification resulted in acceptable prediction performance (AUC > 0.7). This study might inspire new IPC strategies for improving foot microcirculation.

The third-person perspective full-body illusion induced by visual-tactile stimulation in virtual reality for stroke patients.

This paper attempts to induce the third-person perspective full body illusion (3PP-FBI) with virtual reality (VR) in stroke patients. Nineteen individuals with stroke were recruited. The 3PP-FBI induction method, which was well-established in healthy individuals, using synchronous visual-tactile stimulation on one body part was used. Questionnaire scores and proprioceptive drift values were collected under different conditions for characterizing the induced 3PP-FBI. Results showed that synchronous visual-tactile stimulation of a single body part (back or upper limb) was sufficient to elicit 3PP-FBI in stroke patients, forming a sense of ownership (SOO) over the entire virtual body. Moreover, the intensity of 3PP-FBI was stronger when the back was stimulated, compared to stimulating the impaired upper limb. This study demonstrated the viability of visual-guided rehabilitation training while having a SOO to a virtual body from the third-person perspective, in anticipation of achieving better rehabilitation outcome for movements beyond the first-person perspective.

C-Reactive Protein Levels and Cognitive Decline following Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

Cognitive decline (CD) is devastating with a high incidence in patients after stroke. Although some studies have explored underlying associations between C-reactive protein (CRP) levels and cognitive decline after stroke, consistent results have not been obtained. Therefore, this meta-analysis aimed to explore whether or not higher levels of C-reactive proteins were associated with an increased risk of cognitive decline after stroke. To this end, PubMed, Embase, the Cochrane Library, and Web of Science were searched for eligible studies, and pooled effect sizes from eligible studies were calculated using random effect models. Furthermore, subgroups were established and meta-regression analyses were performed to explain the causes of heterogeneity. Eventually, nine studies with 3893 participants were included. Our statistical results suggested that the concentrations of peripheral CRP may be significantly increased for CD patients after stroke, compared to those of non-CD patients. Subgroup analyses showed that CRP was higher in CD than that in non-CD patients when the mini-mental state examination was used. A higher level of CRP in the acute phase of ischemic stroke may suggest an increased risk of CD after stroke. However, these results should be cautiously interpreted because of the limited sample sizes and the diversity of potential confounders in the studies included in this meta-analysis.

Investigation on aortic hemodynamics based on physics-informed neural network.

Pressure in arteries is difficult to measure non-invasively. Although computational fluid dynamics (CFD) provides high-precision numerical solutions according to the basic physical equations of fluid mechanics, it relies on precise boundary conditions and complex preprocessing, which limits its real-time application. Machine learning algorithms have wide applications in hemodynamic research due to their powerful learning ability and fast calculation speed. Therefore, we proposed a novel method for pressure estimation based on physics-informed neural network (PINN). An ideal aortic arch model was established according to the geometric parameters from human aorta, and we performed CFD simulation with two-way fluid-solid coupling. The simulation results, including the space-time coordinates, the velocity and pressure field, were obtained as the dataset for the training and validation of PINN. Nondimensional Navier-Stokes equations and continuity equation were employed for the loss function of PINN, to calculate the velocity and relative pressure field. Post-processing was proposed to fit the absolute pressure of the aorta according to the linear relationship between relative pressure, elastic modulus and displacement of the vessel wall. Additionally, we explored the sensitivity of the PINN to the vascular elasticity, blood viscosity and blood velocity. The velocity and pressure field predicted by PINN yielded good consistency with the simulated values. In the interested region of the aorta, the relative errors of maximum and average absolute pressure were 7.33% and 5.71%, respectively. The relative pressure field was found most sensitive to blood velocity, followed by blood viscosity and vascular elasticity. This study has proposed a method for intra-vascular pressure estimation, which has potential significance in the diagnosis of cardiovascular diseases.

Dimensionality Engineering of Single-Atom Nanozyme for Efficient Peroxidase-Mimicking.

In nature, enzymatic reactions occur in well-functioning catalytic pockets, where substrates bind and react by properly arranging the catalytic sites and amino acids in a three-dimensional (3D) space. Single-atom nanozymes (SAzymes) are a new type of nanozymes with active sites similar to those of natural metalloenzymes. However, the catalytic centers in current SAzymes are two-dimensional (2D) architectures and the lack of collaborative substrate-binding features limits their catalytic activity. Herein, we report a dimensionality engineering strategy to convert conventional 2D Fe-N-4 centers into 3D structures by integrating oxidized sulfur functionalities onto the carbon plane. Our results suggest that oxidized sulfur functionalities could serve as binding sites for assisting substrate orientation and facilitating the desorption of H2O, resulting in an outstanding specific activity of up to 119.77 U mg-1, which is 6.8 times higher than that of conventional FeN4C SAzymes. This study paves the way for the rational design of highly active single-atom nanozymes.

Correlation between supine flexibility and postoperative correction in adolescent idiopathic scoliosis.

BACKGROUND: The preoperative flexibility of the scoliotic spine is a key aspect of surgical planning, as it provides information on the rigidity of the curve, the extent of structural changes, the levels to be fused and the amount of correction. The purpose of this study was to assess whether supine flexibility can be used to predict postoperative correction in patients with adolescent idiopathic scoliosis (AIS) by determining the correlation between these two characteristics. METHODS: A total of 41 AIS patients who underwent surgical treatment between 2018 and 2020 were retrospectively enrolled for analysis. Preoperative and postoperative standing radiographs and preoperative CT images of the entire spine were collected and used to measure supine flexibility and the postoperative correction rate. T tests were used to analyse the differences in supine flexibility and postoperative correction rate between groups. Pearson's product-moment correlation analysis was performed, and regression models were established to determine the correlation between supine flexibility and postoperative correction. Thoracic curves and lumbar curves were analysed independently. RESULTS: Supine flexibility was found to be significantly lower than the correction rate but showed a strong correlation with the postoperative correction rate, with r values of 0.68 for the thoracic curve group and 0.76 for the lumbar curve group. The relationship between supine flexibility and postoperative correction rate could be expressed by linear regression models. CONCLUSION: Supine flexibility can be used to predict postoperative correction in AIS patients. In clinical practice, supine radiographs may be used in place of existing flexibility test techniques.

Boosting Endogenous Copper(I) for Biologically Safe and Efficient Bioorthogonal Catalysis via Self-Adaptive Metal-Organic Frameworks.

As one of the most typical bioorthogonal reactions, the Cu(I)-catalyzed azide-alkyne 1,3-cycloaddition (CuAAC) reaction has received worldwide attention in intracellular transformation of prodrugs due to its high efficiency and selectivity. However, the exogenous Cu catalysts may disturb Cu homeostasis and cause side effects to normal tissues. What is more, the intratumoral Cu(I) is insufficient to efficiently catalyze the intracellular CuAAC reaction due to oncogene-induced labile Cu(I) deficiency. Herein, in order to boost the endogenous Cu(I) level for intracellular drug synthesis through the bioorthogonal reaction, a self-adaptive bioorthogonal catalysis system was constructed by encapsulating prodrugs and sodium ascorbate within adenosine triphosphate aptamer-functionalized metal-organic framework nanoparticles. The system presents specificity to tumor cells and does not require exogenous Cu catalysts, thereby leading to high anti-tumor efficacy and minimal side effects both in vitro and in vivo. This work will open up a new opportunity for developing biosafe and high-performance bioorthogonal catalysis systems.

Integrating Incompatible Nanozyme-Catalyzed Reactions for Diabetic Wound Healing.

Multi-nanozymes are widely applied in disease treatment, biosensing, and other fields. However, most current multi-nanozyme systems exhibit only moderate activity since reaction microenvironments of different nanozyme are often distinct or even incompatible. Conventional assemble strategies are inapplicable for designing multi-nanozymes consisting of incompatible nanozymes. Herein, a versatile fiber-based compartmentalization strategy is developed to construct multi-nanozyme system capable of simultaneously performing incompatible reactions. In this system, the incompatible nanozymes are spatially distributed in distinct compartmentalized fibers, where different microenvironments can be tailored by controlling the doping reagent, endowing each nanozymes with the preferential microenvironments to exhibit their highest activity. As a proof of concept, pH-incompatible peroxidase-like and catalase-like catalytic reactions are tested to verify the feasibility of this strategy. By doping with benzoic acid in the desired location, the two pH-incompatible nanozymes can work simultaneously without interference. Further, it is demonstrated that the oxygen supply and antimicrobial power of the integrated platform can be applied for accelerating diabetic wound healing. It is hoped that this work provides a way to integrate incompatible nanozyme and broadens the application potential of multi-nanozymes.

Analysis of influencing factors of phenanthrene adsorption by different soils in Guanzhong basin based on response surface method.

Adsorption desorption is an important behavior affecting the migration of phenanthrene in soil. In this study, three typical soils of loess, silts and silty sand in Guanzhong Basin, Shaanxi Province, China were used as adsorbents. Batch equilibrium experiments were carried out to study the adsorption desorption kinetics and isotherm of phenanthrene in different soils. Response surface method (RSM) was used to study the effects of temperature, pH, phenanthrene concentration and organic matter content on soil adsorption of phenanthrene. The results showed that after adsorption, the outline of soil particles became more blurred and the degree of cementation increased. The kinetic adsorption of phenanthrene by soil conforms to the quasi second-order kinetic model, and the adsorption desorption isotherm is nonlinear and conforms to the Freundlich model. Due to the difference of soil properties, the adsorption amount of phenanthrene by soil is loess > silty sand > silts. The thermodynamic results show that the adsorption of phenanthrene by soil is spontaneous and endothermic, and the desorption is spontaneous and exothermic. Through RSM, the interaction between phenanthrene concentration and soil organic matter in Loess and silts is significant, and the interaction between temperature and soil organic matter in silty sand is significant. Among the four factors affecting the adsorption rate of loess, silts and silty sand, soil organic matter is the most significant. The theoretical optimum adsorption rates of loess, silts and silty sand are 98.89%, 96.59% and 93.37% respectively.

A DNAzyme-augmented bioorthogonal catalysis system for synergistic cancer therapy.

As one of the representative bioorthogonal reactions, the copper-catalyzed click reaction provides a promising approach for in situ prodrug activation in cancer treatment. To solve the issue of inherent toxicity of Cu(i), biocompatible heterogeneous copper nanoparticles (CuNPs) were developed for the Cu-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. However, the unsatisfactory catalytic activity and off-target effect still hindered their application in biological systems. Herein, we constructed a DNAzyme-augmented and targeted bioorthogonal catalyst for synergistic cancer therapy. The system could present specificity to cancer cells and promote the generation of Cu(i) via DNAzyme-induced value state conversion of DNA-templated ultrasmall CuNPs upon exposure to endogenous H2O2, thereby leading to high catalytic activity for in situ drug synthesis. Meanwhile, DNAzyme could produce radical species to damage cancer cells. The synergy of in situ drug synthesis and chemodynamic therapy exhibited excellent anti-cancer effects and minimal side effects. The study offers a simple and novel avenue to develop highly efficient and safe bioorthogonal catalysts for biological applications.

Clinical Validation of the Differences Between Two-Dimensional Radiography and Three-Dimensional Computed Tomography Image Measurements of the Spine in Adolescent Idiopathic Scoliosis.

OBJECTIVE: The purpose of this study was to investigate differences between measurements of spine on two-dimensional (2D) radiography and three-dimensional (3D) computed tomography (CT) images taken of patients with adolescent idiopathic scoliosis. METHODS: Standard preoperative CT images and posteroanterior (PA) and lateral radiography images were collected prospectively from 43 patients with adolescent idiopathic scoliosis in whom selective spinal fusions were performed. The parameters of interest were the thoracic Cobb angle, lumbar Cobb angle, T4-T12 kyphosis angle, and L1-S1 lordosis (LL) angle. The parameters were measured using 3 separate methods: 3D measurement of CT images (3D measurement), 2D measurement of radiography images (2D measurement), and 2D measurement of radiography images generated by the projection of CT images (2D XP measurement). Significant differences among the results were assessed by comparison T test. RESULTS: The mean difference between the 2D and 2D XP measurements for the thoracic Cobb, lumbar Cobb, T4-T12 kyphotic, and L1-S1 lordotic angles was 8.38°, 7.67°, 8.77°, and 10.18°, respectively. The mean difference between the 2D XP and 3D measurements was -2.81°, -2.78°, -1.29°, and -2.36°, respectively. The mean difference between the 2D and 3D measurements was 5.16°, 4.51°, 6.49°, and 7.37°, respectively. The results showed significant differences (P < 0.05) among the spinal parameters measured using the 2D, 2D XP, and 3D measurement methods on both the coronal and sagittal plane. CONCLUSIONS: Significant differences among the 2D, 2D XP, and 3D measurement methods were observed on both the sagittal plane and coronal plane of the scoliotic spines as a result of variations in posture during imaging and differences in measurement methods.

The Biomechanics Effect of Hamstring Flexibility on the Risk of Osgood-Schlatter Disease.

Background: The relationship between hamstring flexibility and the risk of OSD continues to be a debate, and whether hamstring stretching exercises should be considered as one of the conservative treatments of OSD is still unclear. Objectives: To investigate the relationship between hamstring flexibility and the risk of OSD by assessing the changes of loading on the tibial tuberosity caused by the changes of hamstring optimal lengths. Methods: Experimental data of a young adult running at 4 m/s were used, which were collected by an eight-camera motion capture system together with an instrumented treadmill. Muscle forces were estimated in OpenSim when hamstring optimal lengths changed in the range of 70-130% of the control case in 5% increments. The force and accumulated force of quadriceps muscle were calculated to evaluate the impact of hamstring optimal lengths on the loading on tibial tuberosity. The changes in muscle forces throughout the gait cycle were compared by using statistical parametric mapping (SPM). The average peak force and accumulated force of five gait cycles were compared. Results: Although the maximum force of the quadriceps muscle was slightly affected by changes in hamstring optimal lengths, the accumulated force of quadriceps muscle increased by 21.97% with hamstring optimal lengths decreased by 30% of the control case. The increase of the muscle force mainly occurred in the early stance phase and terminal swing phase (P < 0.05). However, when hamstring optimal lengths were longer than the control, it had a little effect on accumulated force of quadriceps muscle. Conclusions: The results of this study indicate that a shorter hamstring optimal length, which means lack of flexibility, can cause a high accumulated force on tibial tuberosity, thus increasing the risk of OSD. Hamstring stretching exercise is only effective for people with lack of hamstring flexibility.