Prediction and Interpretability of Melting Points of Ionic Liquids Using Graph Neural Networks.

Ionic liquids (ILs) have wide and promising applications in fields such as chemical engineering, energy, and the environment. However, the melting points (MPs) of ILs are one of the most crucial properties affecting their applications. The MPs of ILs are affected by various factors, and tuning these in a laboratory is time-consuming and costly. Therefore, an accurate and efficient method is required to predict the desired MPs in the design of novel targeted ILs. In this study, three descriptor-based machine learning (DBML) models and eight graph neural network (GNN) models were proposed to predict the MPs of ILs. Fingerprints and molecular graphs were used to represent molecules for the DBML and GNNs, respectively. The GNN models demonstrated performance superior to that of the DBML models. Among all of the examined models, the graph convolutional model exhibited the best performance with high accuracy (root-mean-squared error = 37.06, mean absolute error = 28.79, and correlation coefficient = 0.76). Benefiting from molecular graph representation, we built a GNN-based interpretable model to reveal the atomistic contribution to the MPs of ILs using a data-driven procedure. According to our interpretable model, amino groups, S+, N+, and P+ would increase the MPs of ILs, while the negatively charged halogen atoms, S-, and N- would decrease the MPs of ILs. The results of this study provide new insight into the rapid screening and synthesis of targeted ILs with appropriate MPs.

Multimodal Autonomous Locomotion of Liquid Crystal Elastomer Soft Robot.

Self-oscillation phenomena observed in nature serve as extraordinary inspiration for designing synthetic autonomous moving systems. Converting self-oscillation into designable self-sustained locomotion can lead to a new generation of soft robots that require minimal/no external control. However, such locomotion is typically constrained to a single mode dictated by the constant surrounding environment. In this study, a liquid crystal elastomer (LCE) robot capable of achieving self-sustained multimodal locomotion, with the specific motion mode being controlled via substrate adhesion or remote light stimulation is presented. Specifically, the LCE is mechanically trained to undergo repeated snapping actions to ensure its self-sustained rolling motion in a constant gradient thermal field atop a hotplate. By further fine-tuning the substrate adhesion, the LCE robot exhibits reversible transitions between rolling and jumping modes. In addition, the rolling motion can be manipulated in real time through light stimulation to perform other diverse motions including turning, decelerating, stopping, backing up, and steering around complex obstacles. The principle of introducing an on-demand gate control offers a new venue for designing future autonomous soft robots.

KRT17 from skin cells with high glucose stimulation promotes keratinocytes proliferation and migration.

Impaired diabetic wound healing is an important issue in diabetic complications. Proliferation and migration of keratinocytes are major processes of skin wound repair after injury. However, hyperkeratosis can affect the speed of wound healing. Based on the results of preliminary experiments on increased KRT17 expression after high glucose stimulation of human skin tissue cells, a cell model of human immortalized keratinocyte (HaCaT) stimulation with different concentrations of KRT17 was established in vitro, and the promotion in cell proliferation and migration were discovered. KRT17 silencing promoted diabetic wound healing in the db/db diabetic wound model. Transcriptome sequencing (RNA-seq) was performed on HaCaT cells after KRT17 stimulation, and analysis showed significant enrichment in the PI3K-AKT signaling pathway, in which the regulation of cell c-MYB mRNA, a key molecule regulating cell proliferation and migration, was significantly upregulated. In vitro assays showed increased c-MYB expression and enhanced pAKT activity after HaCaT cell stimulation by KRT17. We speculate that KRT17 is upregulated under high glucose and promotes keratinocyte proliferation and migration caused hyperkeratosis, through the c-MYB/PI3K-AKT pathway, contributing to delayed wound healing.

Programming actuation onset of a liquid crystalline elastomer via isomerization of network topology.

Tuning actuation temperatures of liquid crystalline elastomers (LCEs) achieves control of their actuation onsets, which is generally accomplished in the synthesis step and cannot be altered afterward. Multiple actuation onsets in one LCE can be encoded if the post-synthesis regulation of actuation temperature can be spatiotemporally achieved. This would allow realizing a logical time-evolution of actuation, desired for future soft robots. Nevertheless, this task is challenging given the additional need to ensure mesogen alignment required for actuation. We achieved this goal with a topology isomerizable network (TIN) of LCE containing aromatic and aliphatic esters in the mesogenic and amorphous phases, respectively. These two ester bonds can be distinctly activated for transesterification. The homolytic bond exchange between aliphatic esters allows mechanically induced mesogen alignment without affecting the mesogenic phase. Most importantly, the heterolytic exchange between aromatic and aliphatic esters changes the actuation temperature under different conditions. Spatial control of the two mechanisms via a photo-latent catalyst unleashes the freedom in regulating actuation temperature distribution, yielding unusual controllability in actuation geometries and logical sequence. Our principle is generally applicable to common LCEs containing both aromatic and aliphatic esters.

Silencing circular RNA hsa_circABCC1 inhibits osteosarcoma progression through down-regulating HDAC4 via sponging miR-591.

BACKGROUND: Circular RNA (circRNA) has been shown to play an important regulatory role in the development of various cancers, including osteosarcoma (OS). However, the role of circRNA ABCC1 (circABCC1) in OS was still poorly understood. The aim of our study was to investigate the role of circABCC1 in OS progression and its potential molecular mechanisms. METHODS: The expression of circABCC1, microRNA-591 (miR-591) and histone deacetylase 4 (HDAC4) in OS tissues or cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot (WB) analyses. In vitro experiments, the viability, proliferation, apoptosis, migration, invasion and autophagy of U2OS and HOS cells were assessed in vitro using cell counting kit-8 (CCK-8) assay, 5-ethynyl-29-deoxyuridine (EdU) assay, flow cytometry (FCM) assay, transwell migration and invasion assays (transwell) and WB assay, respectively. Interactions between circABCC1 and miR-591, miR-591 and HDAC4 were confirmed using a dual luciferase reporter gene assay system. The oncogenic role of circABCC1 in OS in vivo was examined by establishing a tumor xenograft model. RESULTS: CircABCC1 was significantly elevated in OS tissues (about 3.1-folds) and cells (U2OS (about 2.1-folds) and HOS (about 2.8-folds)) compared with the control (p < .05). Silencing of circABCC1 significantly reduced the viability and proliferation, promoted apoptosis, impaired migration and invasion, and increased autophagy of U2OS and HOS cells (p < .05). In addition, miR-591 was confirmed to be a target of circABCC1, exerting an opposite effect to circABCC1 (p < .05). MiR-591 attenuation in U2OS and HOS cells was able to reply to the inhibition of cell proliferation, migration and invasion as well as promotion of cell apoptosis and autophagy mediated by silencing circABCC1 (p < .05). HDAC4 was verified to be the target gene of miR-591 in U2OS and HOS cells and was regulated by the circABCC1/miR-591 axis (p < .05), and restoration of HDAC4 levels in U2OS and HOS cells was able to restore the altered cellular function caused by silencing circABCC1 (p < .05). In addition, knockdown of circABCC1 attenuated tumor growth in vivo (p < .05). CONCLUSION: Silencing of circABCC1 inhibits osteosarcoma progression by attenuating HDAC4 expression through sponging miR-591.

Ultrasound Radiomics-Guided Iliac Fascia Block on Postoperative Cognitive Dysfunction in Elderly Patients Undergoing Hip Surgery.

Objective: Elderly patients with hip surgery are prone to postoperative cognitive dysfunction (POCD), leading to health management difficulties. This study is aimed at investigating the effect of ultrasound radiomics-guided iliac fascia block on POCD. Methods: A total of 67 cases of patients who had undergone hip joint surgery were divided into a training set (n = 47) and a validation set (radiomics-guided group, n = 20). The patients were intervened with ultrasound radiomics-guided iliac fascia block, and the maximum relevance minimum redundancy sifts out the image omics features obtained from 2D ultrasound images of patients. Another 20 patients undergone general anesthesia served as control. The incidence of POCD, the total amount of fentanyl, the visual analogue score (VAS) at different time points, and the levels of CRP and NSE in plasma were compared between the two groups. Results: The AUC on the training and validation sets were higher than 0.940. The incidence of POCD in the radiomics-guided and general anesthesia group was 5% and 30%, respectively (P = 0.037). Compared with the general anesthesia group, the dosage of fentanyl in the radiomics-guided was lower, the VAS score at 6 h, 1 d, and 2 d after operation was smaller, and the levels of CRP and NSE were lower (all P < 0.05). Conclusions: For elderly patients with hip surgery, the ultrasound radiomics-guided iliac fascia block can reduce the incidence of POCD and improve the effect of nerve block.

Upcycling of dynamic thiourea thermoset polymers by intrinsic chemical strengthening.

Thermoset polymers are indispensable but their environmental impact has been an ever-increasing concern given their typical intractability. Although concepts enabling their reprocessing have been demonstrated, their practical potential is limited by the deteriorated performance of the reprocessed materials. Here, we report a thiourea based thermoset elastomer that can be reprocessed with enhanced mechanical properties. We reveal that the thiourea bonds are dynamic which leads to the reprocessibility. More importantly, they can undergo selective oxidation during high temperature reprocessing, resulting in significant chemical strengthening within certain reprocessing cycles. This is opposite to most polymers for which reprocessing typically results in material deterioration. The possibility of having materials with inherent reprocessing induced performance enhancement points to a promising direction towards polymer recycling.

An Orthogonal Dynamic Covalent Polymer Network with Distinctive Topology Transformations for Shape- and Molecular Architecture Reconfiguration.

Bond exchange in a typical dynamic covalent polymer network allows access to macroscopic shape reconfigurability, but the network architecture is not altered. An alternative possibility is that the network architecture can be designed to switch to various topological states corresponding to different material properties. Achieving both in one network can expand the material scope, but their intrinsically conflicting mechanisms make it challenging. We design a dynamic covalent network that can undergo two orthogonal topological transformations, namely transesterification on the branched chains and olefin metathesis on the mainframe. This allows independent control of the macroscopic shape and molecular architecture. With this design, we illustrate a bottlebrush network with programmable shape and spatially definable mechanical properties. Our strategy paves a way to on-demand regulation of network polymers.

The bioinformatic approach identifies PARM1 as a new potential prognostic factor in osteosarcoma.

Objective: To explore the key factors affecting the prognosis of osteosarcoma patients. Methods: Based on the GEO dataset and differential expression analysis of normal and osteosarcoma tissues, the gene modules related to the prognosis of osteosarcoma patients were screened by WGCNA, and intersecting genes were taken with differential genes, and the risk prognosis model of osteosarcoma patients was constructed by LASSO regression analysis of intersecting genes, and the prognosis-related factors of osteosarcoma patients were obtained by survival analysis, followed by target for validation, and finally, the expression of prognostic factors and their effects on osteosarcoma cell migration were verified by cellular assays and lentiviral transfection experiments. Results: The prognosis-related gene module of osteosarcoma patients were intersected with differential genes to obtain a total of 9 common genes. PARM1 was found to be a prognostic factor in osteosarcoma patients by LASSO regression analysis, followed by cellular assays to verify that PARM1 was lowly expressed in osteosarcoma cells and that overexpression of PARM1 in osteosarcoma cells inhibited cell migration. Pan-cancer analysis showed that PARM1 was lowly expressed in most cancers and that low expression of PARM1 predicted poor prognosis for patients. Conclusion: The data from this study suggest that PARM1 is closely associated with the prognosis of osteosarcoma patients, and PARM1 may serve as a novel potential prognostic target for osteosarcoma, providing a heartfelt direction for the prevention and treatment of osteosarcoma.

The Identified Hub Gene GlcN in Osteoarthritis Progression and Treatment.

BACKGROUND: As a chronic disease, osteoarthritis has caused great trouble to the health of middle-aged and elderly people. Studies have shown that glucosamine (GlcN) can be used to abate the progression and improve this disease. Based on this point of view, we try to verify the connection between GlcN and osteoarthritis and find more effective biomarkers. METHODS: We downloaded the GSE72575 data set from the GEO database, and used the R language to perform DEG analysis on the gene expression profile of the samples. Next, the GO function and the KEGG signaling pathways were analyzed through the DAVID database, and then, the KEGG pathways enriched in the gene set were analyzed based on GSEA. Then, the PPI network of DEGs was constructed based on the STRING online database, and finally, the hub genes were selected by Cytoscape. RESULTS: Three GlcN-treated MH7A cell treatment groups and 3 control groups in the GSE72575 data set were studied. Through analysis, there were 52 DEGs in these samples. Then, through GO, KEGG, and GSEA, regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway, FoxO signaling pathway, JAK-STAT signaling pathway, PI3K-Akt signaling pathway, TGF-beta signaling pathway, and ECM receptor interaction were involved in the regulatory mechanisms of the osteoarthritis pathogenesis. After that, the hub genes IL6 and DDIT3 were identified through PPI network construction and analysis. And it was found that IL6 was lowly expressed in the group with GlcN-treated MH7A cells, while DDIT3 was highly expressed. CONCLUSION: The above results provide a basis for GlcN to participate in the treatment of osteoarthritis and a possibility for finding effective therapeutic targets.

Segmentation of Prefrontal Lobe Based on Improved Clustering Algorithm in Patients with Diabetes.

Diabetics are prone to postoperative cognitive dysfunction (POCD). The occurrence may be related to the damage of the prefrontal lobe. In this study, the prefrontal lobe was segmented based on an improved clustering algorithm in patients with diabetes, in order to evaluate the relationship between prefrontal lobe volume and COPD. In this study, a total of 48 diabetics who underwent selective noncardiac surgery were selected. Preoperative magnetic resonance imaging (MRI) images of the patients were segmented based on the improved clustering algorithm, and their prefrontal volume was measured. The correlation between the volume of the prefrontal lobe and Z-score or blood glucose was analyzed. Qualitative analysis shows that the gray matter, white matter, and cerebrospinal fluid based on the improved clustering algorithm were easy to distinguish. Quantitative evaluation results show that the proposed segmentation algorithm can obtain the optimal Jaccard coefficient and the least average segmentation time. There was a negative correlation between the volume of the prefrontal lobe and the Z-score. The cut-off value of prefrontal lobe volume for predicting POCD was <179.8, with the high specificity. There was a negative correlation between blood glucose and volume of the prefrontal lobe. From the results, we concluded that the segmentation of the prefrontal lobe based on an improved clustering algorithm before operation may predict the occurrence of POCD in diabetics.

Drug-coated balloon angioplasty versus balloon angioplasty for treating patients with in-stent restenosis in the femoropopliteal artery: A meta-analysis.

BACKGROUND: The introduction of endovascular surgery has led to frequent stent use, although in-stent restenosis (ISR) remains a challenging issue. Drug-coated balloon (DCB) and conventional balloon angioplasty (BA) are common endovascular procedures for addressing ISR in the femoropopliteal artery. However, there is controversy regarding which procedure provides the greatest benefit to patients. METHODS: The PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched for prospective controlled trials that compared DCB and BA for patients with ISR in the femoropopliteal artery. The study has been approved by Ethics Committee of Wuhan Central Hospital. RESULTS: The meta-analysis included 6 prospective trials with 541 patients. We found that DCB use was associated with significant reductions in binary restenosis at 6 months (relative risk [RR]: 0.45, 95% confidence interval [CI]: 0.33-0.63; P < .00001), binary restenosis at 1 year (RR: 0.44, 95% CI: 0.34-0.57; P < .00001), target lesion revascularization (TLR) at 6 months (RR: 0.36, 95% CI: 0.20-0.65; P = .0006), and TLR at 1 year (RR: 0.38, 95% CI: 0.27-0.54; P < .00001). The DCB group also had significantly better clinical improvement (RR: 1.39, 95% CI: 1.13-1.71; P = .002), although we did not detect inter-group differences in terms of death, target vessel thrombosis, or ipsilateral amputation. The brand of DCB may a cause of heterogeneity. CONCLUSION: Relative to BA, DCB use increases the durability of treatment for ISR in the femoropopliteal artery, based on significant reductions in binary restenosis and TLR at 6-12 months after the procedure. Furthermore, DCB use was associated with better clinical improvement. However, additional randomized controlled trials are needed to validate these findings.

MicroRNA-15b shuttled by bone marrow mesenchymal stem cell-derived extracellular vesicles binds to WWP1 and promotes osteogenic differentiation.

BACKGROUND: Osteogenic differentiation is an essential process for bone regeneration involving bone marrow mesenchymal stem cells (BMSCs). BMSC-secreted extracellular vesicles (EVs) enriched with microRNAs (miRs) have vital roles to play in mediating osteogenic differentiation. Therefore, this study aimed to explore the effect of BMSC-derived EVs loaded with miR-15b on osteogenic differentiation. METHODS: Human BMSCs (hBMSCs) were cultured and treated with plasmids overexpressing or knocking down KLF2, WWP1, and miR-15b to define the role of derived EVs in osteogenic differentiation in vitro. The expression of osteogenic differentiation-related marker was measured by Western blot analysis. The interaction among miR-15b, WWP1, and ubiquitination of KLF2 was investigated by dual-luciferase reporter, immunoprecipitation, and GST pull-down assays. Moreover, EVs from hBMSCs transfected with miR-15b inhibitor (EV-miR-15b inhibitor) were injected into ovariectomized rats to verify the effect of miR-15b on bone loss in vivo. RESULTS: WWP1 was downregulated, and KLF2 was upregulated during osteogenic differentiation. After co-culture with EVs, miR-15b expression was elevated and WWP1 expression was reduced in hBMSCs. Upregulation of miR-15b or KLF2 or downregulation of WWP1 or NF-κB increased ALP activity and cell mineralization, as well as osteogenic differentiation-related marker expression in hBMSCs. Mechanistically, miR-15b targeted and inhibited WWP1, thus attenuating KLF2 degradation and inhibiting NF-κB activity. Co-culture of EVs increased the bone volume and trabecular number, but decreased bone loss in ovariectomized rats, which could be reversed after treatment with EV-miR-15b inhibitor. CONCLUSION: Collectively, BMSC-derived EVs loaded with miR-15b promoted osteogenic differentiation by impairing WWP1-mediated KLF2 ubiquitination and inactivating the NF-κB signaling pathway.

Circulating Connective Tissue Growth Factor Is Associated with Diastolic Dysfunction in Patients with Diastolic Heart Failure.

BACKGROUND: Connective tissue growth factor (CTGF) and transforming growth factor ß1 (TGF-ß1) are emerging biomarkers for tissue fibrosis. The aim of this study was to investigate the association between circulating CTGF, TGF-ß1 levels and cardiac diastolic dysfunction in patients with diastolic heart failure (DHF). METHODS: Admitted subjects were screened for heart failure and those with left ventricular (LV) ejection fraction <45% were excluded. Diastolic dysfunction was defined as functional abnormalities that exist during LV relaxation and filling by echocardiographic criteria. Totally 114 patients with DHF and 72 controls were enrolled. Plasma levels of CTGF, TGF-ß1, and B-type natriuretic peptide (BNP) were determined. RESULTS: The plasma CTGF and TGF-ß1 levels increased significantly in patients with DHF. Circulating CTGF and TGF-ß1 levels were correlated with echocardiographic parameter E/e' and diastolic dysfunction grading in DHF patients. In multivariate logistic analysis, CTGF was significantly associated with diastolic dysfunction (odds ratio: 1.027, p < 0.001). Plasma CTGF (AUC: 0.770 ± 0.036, p < 0.001) and CTGF/BNP (AUC: 0.839 ± 0.036, p < 0.001) showed good predictive power to the diagnosis of DHF. CONCLUSIONS: This finding suggested CTGF could be involved in the pathophysiology of diastolic heart failure and CTGF/BNP might have auxiliary diagnostic value on diastolic heart failure.

The association between orthostatic blood pressure changes and subclinical target organ damage in subjects over 60 years old.

BACKGROUND: Although recent studies have indicated that both orthostatic hypotension and orthostatic hypertension independently predict cardiovascular events, the underlying mechanisms are still controversial. The aim of the study was to investigate the relationships between orthostatic changes and organ damage in subjects over 60 years old. METHODS: This is a prospective observational cohort study. One thousand nine hundred and ninety-seven subjects over 60 years old were enrolled. Participants were grouped according to whether they had a drop ≥ 20 mmHg in systolic or ≥ 10 mmHg in diastolic BP (orthostatic hypotension), an increase in mean orthostatic systolic blood pressure ≥ 20 mm Hg (orthostatic hypertension), or normal changes within 3 min of orthostatism. Multiple regression modeling was used to investigate the relationship between orthostatic hypotension, orthostatic hypertension and subclinical organ damage with adjustment for confounders. RESULTS: Orthostatic hypotension and orthostatic hypertension were found in 461 (23.1%) and 189 (9.5%) participants, respectively. Measurement of carotid intima-media thickness (IMT), brachial-ankle pulse wave velocity (baPWV), clearance of creatinine, and microalbuminuria were associated with orthostatic hypotension; measurement of IMT and baPWV were associated with orthostatic hypertension in a cruse model. After adjustment, IMT [odds ratio (OR), 95% confidence interval (CI) per one-SD increment: 1.385, 1.052-1.823; P = 0.02], baPWV (OR = 1.627, 95% CI: 1.041-2.544; P = 0.033) and microalbuminuria (OR = 1.401, 95% CI: 1.002-1.958; P = 0.049) were still associated with orthostatic hypotension, while orthostatic hypertension was only associated with IMT (OR = 1.730, 95% CI: 1.143-2.618; P = 0.009). CONCLUSIONS: Orthostatic hypotension seems to be independently correlated with increased carotid atherosclerosis, arterial stiffness and renal damage in subjects over 60 years old. Orthostatic hypertension correlates with carotid atherosclerosis only.

Misinterpretation of allergic bronchopulmonary aspergillosis/allergic bronchopulmonary mycosis due to diverse characteristics in different clinical stages.

BACKGROUND: Allergic bronchopulmonary mycosis (ABPM) is a complex pulmonary disorder caused by a hyperimmune response to the endobronchial growth of certain fungi. This study aims to aid physicians in better understanding the need for earlier recognition of ABPM. METHODS: Patients with a confirmed diagnosis of ABPM after evaluation were analyzed retrospectively. Clinical features, previous diagnoses and potential diagnostic errors, laboratory findings were reviewed and compiled. RESULTS: Fifty-seven patients were diagnosed with ABPM in which 22 were misdiagnosed. Eosinophilia was observed in 11 patients and an elevated total serum Ig E level greater than 1,000 kU/L was detected in 25 of the 57 patients. All of the patients were tested for specific Ig E in which positive to different fungi. The two most common abnormalities found on chest high-resolution computed tomography (HRCT) exams were central bronchiectasis and mucus plugs. A mild to moderate obstructive pattern of lung function was observed in 32 cases. By bronchofiberscopic observation, bronchial lumen was seen to have significant inflammation in 12 patients. After 3 weeks of treatment, a decreased serum total Ig E value was observed. CONCLUSIONS: This study highlights the importance of increasing awareness and understanding of non-Aspergillus-ABPM among physicians and draws attention to the need for establishing more elaborate diagnostic criteria for non-Aspergillus-ABPM, which is a rare kind of disease.

HOXA5 overexpression promotes osteosarcoma cell apoptosis through the p53 and p38α MAPK pathway.

Osteosarcoma is the most common malignant bone tumor in children and adolescents. Aberrant expression of HOXA5 results in various diseases, including cancers. However, the specific function and molecular mechanism of HOXA5 in osteosarcoma is not fully understood. In the present study, we focused on HOXA5 in U2OS and MG63 cells in vitro. We observed lower expression of HOXA5 in U2OS, MG63, and SaOS2 human osteosarcoma cells, compared with hFOB1.19 human osteoblastic cells. HOXA5 overexpression in U2OS and MG63 cells markedly reduced cell survival and proliferation and elevated cell apoptosis and caspase-3 activity. HOXA5 also activated the p38α MAPK pathway by increasing p53. Treating U2OS and MG63 cells with the p53 inhibitor α-pifithrin or the p38α MAPK inhibitor SB203580 led to higher cell survival and proliferation and lower cell apoptosis, compared with the pcDNA3.1-HOXA5 group. In conclusion, our study showed that the p53 and p38α MAPK signal axis facilitated HOXA5's role in inhibiting growth and stimulating apoptosis of osteosarcoma cells.