Identification of Diagnostic Magnetic Resonance Imaging Findings in 47 Shoulders with Subcoracoid Impingement Syndrome by Comparison with 100 Normal Shoulders.

BACKGROUND The aim of this study was to identify the diagnostic magnetic resonance imaging (MRI) findings in 47 shoulders with subcoracoid impingement syndrome by comparison with 100 normal shoulders. MATERIAL AND METHODS The subcoracoid impingement syndrome group consisted of 47 shoulders with subcoracoid impingement syndrome and the normal group consisted of 100 normal shoulders. The MRI parameters - coracoids-humeral distance (CHD), coracoid index (CI), height of the lesser tuberosity (HLT), coracoid obliquity (CO), coracoglenoid angle (CGA), coracohumeral angle (CHA), width of the subscapular tendon (WST), and contact distance between subscapular tendon and coracoid process (CD) - were compared between the subcoracoid impingement syndrome group and the normal group. The areas under the curves (AUCs) from the receiver operating characteristic (ROC) for single MRI parameters were recorded, in which the MRI parameters with AUC exceeding 0.70 were included in the analysis of combined parameters. Comparisons of ROC were made among single parameters and combined parameters. RESULTS For diagnosing subcoracoid impingement syndrome by using single MRI parameters (CHD, CI, HLT, CGA, CHA, WST, and CD), the AUCs were 0.963, 0.806, 0.745, 0.691, 0.613, 0.685, and 0.614, respectively, of which CHD had the largest AUC. CHD, CI, and HLT (AUC exceeding 0.70) were included in the study of the combined parameters. The AUC of combined CHD and HLT showed a significantly larger AUC than that of CHD (0.986 vs 0.963, P=0.036), and showed no significant difference compared with that of combined CHD, CI, and HLT (0.986 vs 0.987, P=0.882). CONCLUSIONS Measurement of the coracoid-humeral distance and height of the lesser tuberosity were key MRI diagnostic findings for subcoracoid impingement syndrome.

Regulating the Distribution and Accumulation of Charged Molecules by Progressive Electroporation for Improved Intracellular Delivery.

The cell membrane separates the intracellular compartment from the extracellular environment, constraining exogenous molecules to enter the cell. Conventional electroporation typically employs high-voltage and short-duration pulses to facilitate the transmembrane transport of molecules impermeable to the membrane under natural conditions by creating temporary hydrophilic pores on the membrane. Electroporation not only enables the entry of exogenous molecules but also directs the intracellular distribution of the electric field. Recent advancements have markedly enhanced the efficiency of intracellular molecule delivery, achieved through the utilization of microstructures, microelectrodes, and surface modifications. However, little attention is paid to regulating the motion of molecules during and after passing through the membrane to improve delivery efficiency, resulting in an unsatisfactory delivery efficiency and high dose demand. Here, we proposed the strategy of regulating the motion of charged molecules during the delivery process by progressive electroporation (PEP), utilizing modulated electric fields. Efficient delivery of charged molecules with an expanded distribution and increased accumulation by PEP was demonstrated through numerical simulations and experimental results. The dose demand can be reduced by 10-40% depending on the size and charge of the molecules. We confirmed the safety of PEP for intracellular delivery in both short and long terms through cytotoxicity assays and transcriptome analysis. Overall, this work not only reveals the mechanism and effectiveness of PEP-enhanced intracellular delivery of charged molecules but also suggests the potential integration of field manipulation of molecular motion with surface modification techniques for biomedical applications such as cell engineering and sensitive cellular monitoring.

Glioblastoma behavior study under different frequency electromagnetic field.

The tumor-treating fields (TTFields) technology has revolutionized the management of recurrent and newly diagnosed glioblastoma (GBM) cases. To ameliorate this treatment modality for GBM and other oncological conditions, it is necessary to understand the biophysical principles of TTFields better. In this study, we further analyzed the mechanism of the electromagnetic exposure with varying frequencies and electric field strengths on cells in mitosis, specifically in telophase. In reference to previous studies, an intuitive finite element model of the mitotic cell was built for electromagnetic simulations, predicting a local increase in the cleavage furrow region, which may help explain TTFields' anti-proliferative effects. Cell experiments confirmed that the reduction in proliferation and migration of glioma cell by TTFields was in a frequency- and field-strength-dependent manner. This work provides unique insights into the selection of frequencies in the anti-proliferative effect of TTFields on tumors, which could improve the application of TTFields.

Neural stem cell transplantation alleviates functional cognitive deficits in a mouse model of tauopathy.

The mechanisms of the transplantation of neural stem cells (NSCs) in the treatment of Alzheimer's disease remain poorly understood. In this study, NSCs were transplanted into the hippocampal CA1 region of the rTg (tau P301L) 4510 mouse model, a tauopathy model that is thought to reflect the tau pathology associated with Alzheimer's disease. The results revealed that NSC transplantation reduced the abnormal aggregation of tau, resulting in significant improvements in the short-term memory of the tauopathy model mice. Compared with wild-type and phosphate-buffered saline (PBS)-treated mice, mice that received NSC transplantations were characterized by changes in the expression of multiple proteins in brain tissue, particularly those related to the regulation of tau aggregation or misfolding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) function analysis revealed that these proteins were primarily enriched in pathways associated with long-term potentiation, neurogenesis, and other neurobiological processes. Changes in the expression levels of key proteins were verified by western blot assays. These data provided clues to improve the understanding of the functional capacity associated with NSC transplantation in Alzheimer's disease treatment. This study was approved by the Beijing Animal Ethics Association and Ethics Committee of Beijing Institute of Technology (approval No. SYXK-BIT-school of life science-2017-M03) in 2017.

Mutations of beta-amyloid precursor protein alter the consequence of Alzheimer's disease pathogenesis.

Alzheimer's disease is pathologically defined by accumulation of extracellular amyloid-ß (Aß). Approximately 25 mutations in ß-amyloid precursor protein (APP) are pathogenic and cause autosomal dominant Alzheimer's disease. To date, the mechanism underlying the effect of APP mutation on Aß generation is unclear. Therefore, investigating the mechanism of APP mutation on Alzheimer's disease may help understanding of disease pathogenesis. Thus, APP mutations (A673T, A673V, E682K, E693G, and E693Q) were transiently co-transfected into human embryonic kidney cells. Western blot assay was used to detect expression levels of APP, beta-secretase 1, and presenilin 1 in cells. Enzyme-linked immunosorbent assay was performed to determine Aß1-40 and Aß1-42 levels. Liquid chromatography-tandem mass chromatography was used to examine VVIAT, FLF, ITL, VIV, IAT, VIT, TVI, and VVIA peptide levels. Immunofluorescence staining was performed to measure APP and early endosome antigen 1 immunoreactivity. Our results show that the protective A673T mutation decreases Aß42/Aß40 rate by downregulating IAT and upregulating VVIA levels. Pathogenic A673V, E682K, and E693Q mutations promote Aß42/Aß40 rate by increasing levels of CTF99, Aß42, Aß40, and IAT, and decreasing VVIA levels. Pathogenic E693G mutation shows no significant change in Aß42/Aß40 ratio because of inhibition of γ-secretase activity. APP mutations can change location from the cell surface to early endosomes. Our findings confirm that certain APP mutations accelerate Aß generation by affecting the long Aß cleavage pathway and increasing Aß42/40 rate, thereby resulting in Alzheimer's disease.