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Background: Nonischemic cardiomyopathy (NISCM) is a clinical challenge with limited therapeutic targets. This study aims to identify promising drug targets for NISCM. Methods: We utilized cis-pQTLs from the deCODE study, which includes data from 35,559 Icelanders, and SNPs from the FinnGen study, which includes data from 1,754 NISCM cases and 340,815 controls of Finnish ancestry. Mendelian randomization (MR) analysis was performed to estimate the causal relationship between circulating plasma protein levels and NISCM risk. Proteins with significant associations underwent false discovery rate (FDR) correction, followed by Bayesian colocalization analysis. The expression of top two proteins, LILRA5 and NELL1, was further analyzed using various NISCM datasets. Descriptions from the Human Protein Atlas (HPA) validated protein expression. The impact of environmental exposures on LILRA5 was assessed using the Comparative Toxicogenomics Database (CTD), and molecular docking identified the potential small molecule interactions. Results: MR analysis identified 255 circulating plasma proteins associated with NISCM, with 16 remaining significant after FDR correction. Bayesian colocalization analysis identified LILRA5 and NELL1 as significant, with PP.H4 > 0.8. LILRA5 has a protective effect (OR = 0.758, 95% CI, 0.670–0.857) while NELL1 displays the risk effect (OR = 1.290, 95% CI, 1.199–1.387) in NISCM. Decreased LILRA5 expression was found in NISCM such as diabetic, hypertrophic, dilated, and inflammatory cardiomyopathy, while NELL1 expression increased in hypertrophic cardiomyopathy. HPA data indicated high LILRA5 expression in neutrophils, macrophages and endothelial cells within normal heart and limited NELL1 expression. Immune infiltration analysis revealed decreased neutrophil in diabetic cardiomyopathy. CTD analysis identified several small molecules that affect LILRA5 mRNA expression. Among these, Estradiol, Estradiol-3-benzoate, Gadodiamide, Topotecan, and Testosterone were found to stably bind to the LILRA5 protein at the conserved VAL-15 or THR-133 residues in the Ig-like C2 domain. Conclusion: Based on European Ancestry Cohort, this study reveals that LILRA5 and NELL1 are potential therapeutic targets for NISCM, with LILRA5 showing particularly promising prospects in diabetic cardiomyopathy. Several small molecules interact with LILRA5, implying potential clinical implication. [ABSTRACT FROM AUTHOR]

Traveling wave rotary ultrasonic motors (TRUSMs) have been applied in optical systems, robotics, biomedical and other fields. However, the disadvantages such as short working life, driving performance degradation, and low energy utilization significantly limit the long-term and stable operation of TRUSMs in advanced fields like aerospace mechanisms. To address the above issues, a novel rotary ultrasonic motor based on multiple Langevin transducers is proposed in this paper. First, the structural design, driving principle and general design criteria are described in detail. Then, the structural parameters are optimized by finite element simulation analysis. Second, a prototype is assembled controllably. Subsequently, the impedance test and vibration measurement are carried out. The results show that the traveling wave is successfully generated on the tooth-ring, and all the Langevin transducers are excited to the first-order longitudinal vibration modes, which strongly verify the correctness of design principle. Finally, the driving performance experiment is carried out. The experimental results show that the no-load speed is 62 r min−1 under the pre-pressure of 10 N. The stalling torque is 0.94 N m at the driving voltage of 500 Vp-p. The response characteristics show that the start/stop time are 4.6/5.5 ms, and the angular displacement resolution of clockwise/counterclockwise driving are 6.7/10.2 μ rad. The motor proposed in this paper not only exhibits relatively high output performance with excellent vibration characteristics, but also maintains compactness of the structure. The sandwiched structure design effectively avoids the problem that the bonded-type piezoceramic rings in conventional TRUSMs are prone to damage or fall-off when vibrating for a long time. Furthermore, the general design criteria provide a new approach to develop high performance rotary ultrasonic motors. The proposed novel ultrasonic motor is expected to meet the demand for long-term and stable operation in aerospace mechanisms. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical value of video-electroencephalography (VEEG) and thermal stimulus on evaluating the prognosis of comatose patients after cardiopulmonary resuscitation. Methods: Twenty eight comatose patients with cardiopulmonary resuscitation were included in the department of ICU of the First Teaching Hospital of Fujian Medical University from February 2013 to March 2016. Of the included 28 patients, 20 cases died (death group) and 8 cases survived (survival group) after cardiopulmonary resuscitation. The VEEG, Glasgow Coma Scale (GCS) and APACHE II score were recorded and compared between the death and survival group. The prediction value of death for VEEG, GCS and APACHE II were evaluated through sensitivity, specificity and area under the receiver operating characteristic (ROC) curve (AUC). Results: GCS and APACHEH II score were statistical different between the death and survival group (P<0.05). With the increase of VEEG grading, the mortality rate of patients increased significantly (P<0.05). Predicting value of mortality for GCS, VEEG and APACHEH II were 57.69%, 61.54% and 71.43% respectively without statistical difference (P>0.05). The death prediction sensitivity and specificity for GCS were 67.0% and 85.0%, for APACHEH II were 95.1% and 85.0%, for VEEG were 100.0% and 85.2%. VEEG has the highest sensitivity, Specificity, coincidence rate and Kappa vale compared to GCS, and APACHEH II. Conclusion: Video-electroencephalography is a useful tool for predicting the death risk for patients who received cardiopulmonary resuscitation. [ABSTRACT FROM AUTHOR]

Introduction: Hydrocephalus is a common pediatric disorder of cerebral spinal fluid physiology resulting in abnormal expansion of the cerebral ventricles. However, the underlying molecular mechanisms remain unknown., Methods: We performed proteomic analyses of cerebrospinal fluid (CSF) from 7 congenital hydrocephalus and 5 arachnoid cyst patients who underwent surgical treatment. Differentially expressed proteins (DEPs) were identified by label-free Mass Spectrometry followed by differential expression analysis. The GO and GSEA enrichment analysis was performed to explore the cancer hallmark pathways and immune-related pathways affected by DEPs. Then, network analysis was applied to reveal the location of DEPs in the human protein-protein interactions (PPIs) network. Potential drugs for hydrocephalus were identified based on drug-target interaction., Results: We identified 148 up-regulated proteins and 82 down-regulated proteins, which are potential biomarkers for clinical diagnosis of hydrocephalus and arachnoid cyst. Functional enrichment analysis revealed that the DEPs were significantly enriched in the cancer hallmark pathways and immunerelated pathways. In addition, network analysis uncovered that DEPs were more likely to be located in the central regions of the human PPIs network, suggesting DEPs may be proteins that play important roles in human PPIs. Finally, we calculated the overlap of drug targets and the DEPs based on drugtarget interaction to identify the potential therapeutic drugs of hydrocephalus., Conclusion: The comprehensive proteomic analyses provided valuable resources for investigating the molecular pathways in hydrocephalus, and uncovered potential biomarkers for clinical diagnosis and therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)