AiroTouch: enhancing telerobotic assembly through naturalistic haptic feedback of tool vibrations.

Teleoperation allows workers to safely control powerful construction machines; however, its primary reliance on visual feedback limits the operator's efficiency in situations with stiff contact or poor visibility, hindering its use for assembly of pre-fabricated building components. Reliable, economical, and easy-to-implement haptic feedback could fill this perception gap and facilitate the broader use of robots in construction and other application areas. Thus, we adapted widely available commercial audio equipment to create AiroTouch, a naturalistic haptic feedback system that measures the vibration experienced by each robot tool and enables the operator to feel a scaled version of this vibration in real time. Accurate haptic transmission was achieved by optimizing the positions of the system's off-the-shelf accelerometers and voice-coil actuators. A study was conducted to evaluate how adding this naturalistic type of vibrotactile feedback affects the operator during telerobotic assembly. Thirty participants used a bimanual dexterous teleoperation system (Intuitive da Vinci Si) to build a small rigid structure under three randomly ordered haptic feedback conditions: no vibrations, one-axis vibrations, and summed three-axis vibrations. The results show that users took advantage of both tested versions of the naturalistic haptic feedback after gaining some experience with the task, causing significantly lower vibrations and forces in the second trial. Subjective responses indicate that haptic feedback increased the realism of the interaction and reduced the perceived task duration, task difficulty, and fatigue. As hypothesized, higher haptic feedback gains were chosen by users with larger hands and for the smaller sensed vibrations in the one-axis condition. These results elucidate important details for effective implementation of naturalistic vibrotactile feedback and demonstrate that our accessible audio-based approach could enhance user performance and experience during telerobotic assembly in construction and other application domains.

Alpha-lipoic acid impedes myocardial ischemia-reperfusion injury, myocardial apoptosis, and oxidative stress by regulating HMGB1 expression.

BACKGROUND: Inflammation, oxidative stress, and apoptosis contribute to myocardial ischemia/reperfusion injury (I/RI). Alpha-lipoic acid (ALA) plays a critical role in I/RI by impeding apoptosis and inflammation. Here, we aimed to explore the underlying mechanisms of ALA after I/RI. METHODS: The left anterior descending coronary artery (LAD) was ligated, and H9c2 cells were exposed to hypoxia/reoxygenation (H/R) to establish an I/RI model. Prior to this, H9c2 cells and rats were treated using an appropriate amount of ALA. The cardiac function, inflammatory factors, and myocardial pathology were assessed in vitro. We detected cell viability, apoptosis, and oxidative stress-related factors in vivo. Moreover, proteins of the HMGB1/TLR4/NF-κB signaling pathway were detected both in vivo and in vitro. RESULTS: We observed that ALA increased cell viability in vitro and decreased apoptosis in vitro and in vivo. ALA inhibited reactive oxygen species production, decreased malondialdehyde, and increased superoxide dismutase activity to resist oxidative stress in vitro. ALA also reduced the expression of inflammatory cytokines (IL-6, IL-1ß, and TNF-α) in vivo. ALA also suppressed the levels of the apoptotic protein, Bax, and increased the expression of the anti-apoptotic protein Bcl-2, in vitro and in vivo. Moreover, we observed that ALA significantly inhibited the cytoplasmic localization of HMGB1, which might attenuate MI/RI or H/R via HMGB1/TLR4/NF-κB pathway. CONCLUSION: ALA regulates HMGB1 translocation and attenuates I/R via the HMGB1/TLR4/NF-κB signaling pathway, thus impeding apoptosis, oxidation, and inflammation, and might be a potential target for myocardial ischemia/reperfusion injury.

Human Plasma Transcriptome Implicates Dysregulated S100A12 Expression: A Strong, Early-Stage Prognostic Factor in ST-Segment Elevated Myocardial Infarction: Bioinformatics Analysis and Experimental Verification.

The ability of blood transcriptome analysis to identify dysregulated pathways and outcome-related genes following myocardial infarction remains unknown. Two gene expression datasets (GSE60993 and GSE61144) were downloaded from Gene Expression Omnibus (GEO) Datasets to identify altered plasma transcriptomes in patients with ST-segment elevated myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. GEO2R, Gene Ontology/Kyoto Encyclopedia of Genes and Genomes annotations, protein-protein interaction analysis, etc., were adopted to determine functional roles and regulatory networks of differentially expressed genes (DEGs). Dysregulated expressomes were verified at transcriptional and translational levels by analyzing the GSE49925 dataset and our own samples, respectively. A total of 91 DEGs were identified in the discovery phase, consisting of 15 downregulated genes and 76 upregulated genes. Two hub modules consisting of 12 hub genes were identified. In the verification phase, six of the 12 hub genes exhibited the same variation patterns at the transcriptional level in the GSE49925 dataset. Among them, S100A12 was shown to have the best discriminative performance for predicting in-hospital mortality and to be the only independent predictor of death during follow-up. Validation of 223 samples from our center showed that S100A12 protein level in plasma was significantly lower among patients who survived to discharge, but it was not an independent predictor of survival to discharge or recurrent major adverse cardiovascular events after discharge. In conclusion, the dysregulated expression of plasma S100A12 at the transcriptional level is a robust early prognostic factor in patients with STEMI, while the discrimination power of the protein level in plasma needs to be further verified by large-scale, prospective, international, multicenter studies.

The Key Genes Underlying Pathophysiology Association between Plaque Instability and Progression of Myocardial Infarction.

Young patients with type 2 diabetes and myocardial infarction (MI) have higher long-term all-cause and cardiovascular mortality. In addition, the observed increased, mildly abnormal baseline lipid levels, but not lipid variability, are associated with an increased risk of atherosclerotic cardiovascular disease events, particularly MI. This study investigated differentially expressed genes (DEGs), which might be potential targets for young patients with MI and a high-fat diet (HFD). GSE114695 and GSE69187 were downloaded and processed using the limma package. A Venn diagram was applied to identify the same DEGs, and further pathway analysis was performed using Metascape. Protein-protein interaction (PPI) network analysis was then applied, and the hub genes were screened out. Pivotal miRNAs were predicted and validated using the miRNA dataset in GSE114695. To investigate the cardiac function of the screened genes, an MI mouse model, echocardiogram, and ELISA of hub genes were applied, and a correlation analysis was also performed. From aged mice fed HFD, 138 DEGs were extracted. From aged mice fed with chow, 227 DEGs were extracted. Pathway enrichment analysis revealed that DEGs in aging mice fed HFD were enriched in lipid transport and lipid biosynthetic process 1 d after MI and in the MAPK signaling pathway at 1 w after MI, suggesting that HFD has less effect on aging with MI. A total of 148 DEGs were extracted from the intersection between plaques fed with HFD and chow in young mice and MI_1d, respectively, which demonstrated increased inflammatory and adaptive immune responses, in addition to myeloid leukocyte activation. A total of 183 DEGs were screened out between plaques fed with HFD vs. chow in young mice and MI_1w, respectively, which were mainly enriched in inflammatory response, cytokine production, and myeloid leukocyte activation. After validation, PAK3, CD44, CD5, SOCS3, VAV1, and PIK3CD were demonstrated to be negatively correlated with LVEF; however, P2RY1 was demonstrated to be positively correlated. This study demonstrated that the screened hub genes may be therapeutic targets for treating STEMI patients and preventing MI recurrence, especially in young MI patients with HFD or diabetes.

X-box binding protein 1-mediated COL4A1s secretion regulates communication between vascular smooth muscle and stem/progenitor cells.

Vascular smooth muscle cells (VSMCs) contribute to the deposition of extracellular matrix proteins (ECMs), including Type IV collagen, in the vessel wall. ECMs coordinate communication among different cell types, but mechanisms underlying this communication remain unclear. Our previous studies have demonstrated that X-box binding protein 1 (XBP1) is activated and contributes to VSMC phenotypic transition in response to vascular injury. In this study, we investigated the participation of XBP1 in the communication between VSMCs and vascular progenitor cells (VPCs). Immunofluorescence and immunohistology staining revealed that Xbp1 gene was essential for type IV collagen alpha 1 (COL4A1) expression during mouse embryonic development and vessel wall ECM deposition and stem cell antigen 1-positive (Sca1+)-VPC recruitment in response to vascular injury. The Western blot analysis elucidated an Xbp1 gene dose-dependent effect on COL4A1 expression and that the spliced XBP1 protein (XBP1s) increased protease-mediated COL4A1 degradation as revealed by Zymography. RT-PCR analysis revealed that XBP1s in VSMCs not only upregulated COL4A1/2 transcription but also induced the occurrence of a novel transcript variant, soluble type IV collagen alpha 1 (COL4A1s), in which the front part of exon 4 is joined with the rear part of exon 42. Chromatin-immunoprecipitation, DNA/protein pulldown and in vitro transcription demonstrated that XBP1s binds to exon 4 and exon 42, directing the transcription from exon 4 to exon 42. This leads to transcription complex bypassing the internal sequences, producing a shortened COL4A1s protein that increased Sca1+-VPC migration. Taken together, these results suggest that activated VSMCs may recruit Sca1+-VPCs via XBP1s-mediated COL4A1s secretion, leading to vascular injury repair or neointima formation.

Zebrafish hhatla is involved in cardiac hypertrophy.

Cardiac hypertrophy is a compensatory response to pathological stimuli, ultimately progresses to cardiomyopathy, heart failure, or sudden death. Although many signaling pathways have been reported to be involved in the hypertrophic process, it is still not fully clear about the underlying molecular mechanisms for cardiac hypertrophy. Hedgehog acyltransferase-like (Hhatl), a sarcoplasmic reticulum-resident protein, exhibits high expression in the heart and muscle. However, the biological role of Hhatl in the heart remains unknown. In this study, we first found that the expression level of Hhatl is markedly decreased in cardiac hypertrophy. We further studied the role of hhatla, homolog of Hhatl with the zebrafish model. The depletion of hhatla in zebrafish leads to cardiac defects, as well as an enhanced level of hypertrophic markers. Besides, we found that calcineurin signaling participates in hhatla depletion-induced cardiac hypertrophy. Together, these results demonstrate a critical role for hhatla in cardiac hypertrophy.

ndufa7 plays a critical role in cardiac hypertrophy.

Cardiac hypertrophy is a common pathological change in patients with progressive cardiac function failure, which can be caused by hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) or arterial hypertension. Despite years of study, there is still limited knowledge about the underlying molecular mechanisms for cardiac hypertrophy. NDUFA7, a subunit of NADH:ubiquinone oxidoreductase (complex I), has been reported to be a novel HCM associated gene. However, the biological role of NDUFA7 in heart remains unknown. In this study, we found that NDUFA7 exhibited high expression in the heart, and its level was significantly decreased in mice model of cardiac hypertrophy. Moreover, we demonstrated that ndufa7 knockdown in developing zebrafish embryos resulted in cardiac development and functional defects, associated with increased expression of pathological hypertrophy biomarkers nppa (ANP) and nppb (BNP). Mechanistic study demonstrated that ndufa7 depletion promoted ROS production and calcineurin signalling activation. Moreover, NDUFA7 depletion contributed to cardiac cell hypertrophy. Together, these results report for the first time that ndufa7 is implicated in pathological cardiac hypertrophy.