Balance Evaluation Based on Walking Experiments with Exoskeleton Interference.

The impairment of walking balance function seriously affects human health and will lead to a significantly increased risk of falling. It is important to assess and improve the walking balance of humans. However, existing evaluation methods for human walking balance are relatively subjective, and the selected metrics lack effectiveness and comprehensiveness. We present a method to construct a comprehensive evaluation index of human walking balance. We used it to generate personal and general indexes. We first pre-selected some preliminary metrics of walking balance based on theoretical analysis. Seven healthy subjects walked with exoskeleton interference on a treadmill at 1.25 m/s while their ground reaction force information and kinematic data were recorded. One subject with Charcot-Marie-Tooth walked at multiple speeds without the exoskeleton while the same data were collected. Then, we picked a number of effective evaluation metrics based on statistical analysis. We finally constructed the Walking Balance Index (WBI) by combining multiple metrics using principal component analysis. The WBI can distinguish walking balance among different subjects and gait conditions, which verifies the effectiveness of our method in evaluating human walking balance. This method can be used to evaluate and further improve the walking balance of humans in subsequent simulations and experiments.

Comprehensive Application of XFEL Microcrystallography for Challenging Targets in Various Organic Compounds.

There is a growing demand for structure determination from small crystals, and the three-dimensional electron diffraction (3D ED) technique can be employed for this purpose. However, 3D ED has certain limitations related to the crystal thickness and data quality. We here present the application of serial X-ray crystallography (SX) with X-ray free electron lasers (XFELs) to small (a few µm or less) and thin (a few hundred nm or less) crystals of novel compounds dispersed on a substrate. For XFEL exposures, two-dimensional (2D) scanning of the substrate coupled with rotation enables highly efficient data collection. The recorded patterns can be successfully indexed using lattice parameters obtained through 3D ED. This approach is especially effective for challenging targets, including pharmaceuticals and organic materials that form preferentially oriented flat crystals in low-symmetry space groups. Some of these crystals have been difficult to solve or have yielded incomplete solutions using 3D ED. Our extensive analyses confirmed the superior quality of the SX data regardless of crystal orientations. Additionally, 2D scanning with XFEL pulses gives an overall distribution of the samples on the substrate, which can be useful for evaluating the properties of crystal grains and the quality of layered crystals. Therefore, this study demonstrates that XFEL crystallography has become a powerful tool for conducting structure studies of small crystals of organic compounds.

Dandelion-Like Tailorable Nanoparticles for Tumor Microenvironment Modulation.

Tumor-associated macrophages (TAMs) constitute over 50% of the number of cells within the tumor, playing a major role in tumor progression and invasion. Remodeling the tumor immune microenvironment by modulating TAM polarization has been emerging as a new and promising therapeutic strategy. However, the high interstitial fluid pressure and dense extracellular matrix lead to insufficient penetration of nanosized therapies. To overcome this dilemma, an acid-triggered size-changeable nanoparticle (aptamer/acid sensitive linker crosslinked DGL/zoledronic acid, i.e., Apt@(DGL-ZA) n NPs) with effective tumor distribution, extravasation, and penetration is designed. Dendrigraft poly-L-lysines (DGLs) which can induce tumor autophagy as mimics of natural abnormal proteins are crosslinked via a mild-acid-responsive linker (1,6-bis(4-formylbenzoyloxy) hexane). Long circulation property and tumor penetration are achieved simultaneously by catching DGLs in neutral pH while releasing them in the tumor's pH, like dandelion seeds in midair. The macrophage conditioning agent zoledronic acid (ZA) is loaded on DGLs by the charge attraction. A Tenascin-C targeting aptamer (GBI-10) is modified onto (DGL-ZA) n NPs for a tumor-homing effect. Apt@(DGL-ZA) n NPs show both enhanced penetration in in vitro 3D triple negative breast cancer spheroids and in vivo tumor tissues. Effective macrophage regulation, enhanced tumor autophagy, and excellent in vivo antitumor efficacy are achieved, suggesting this tactic as a significant antitumor strategy.