Ultra-Low Loading of Ultra-Small Fe3 O4 Nanoparticles on Nonmodified CNTs to Improve Green EMI Shielding Capability of Rubber Composites.

From a material design perspective, the incorporation of Fe3 O4 @carbon nanotube (Fe3 O4 @CNT) hybrids is an effective approach for reconciling the contradictions of high shielding and low reflection coefficients, enabling the fabrication of green shielding materials and reducing the secondary electromagnetic wave pollution. However, the installation of Fe3 O4 nanoparticles on nonmodified and nondestructive CNT walls remains a formidable challenge. Herein, a novel strategy for fabricating the above-mentioned Fe3 O4 @CNTs and subsequently assembling segregated Fe3 O4 @CNT networks in natural rubber (NR) matrices is proposed. The advanced and unique structure, magnetism, and lossless conductivity endow the as-obtained Fe3 O4 @CNT/NR with a shielding effectiveness (SE) of 63.8 dB and a low reflection coefficient of 0.24, which indicates a prominent green-shielding capability that surpasses those of previously reported green-shielding materials. Moreover, the specific SE reaches 531 dB cm-1 , exceeding that of those of previously reported carbon/polymer composites. Meanwhile, the outstanding conductivity enables the composite to reach a saturation temperature of ≈95 °C at a driving voltage of 1.5 V with long-term stability. Therefore, the as-fabricated Fe3 O4 @CNT/rubber composites represent an important development in green-shielding materials that are applied in cold environment.

Bone marrow mesenchymal stem cell exosome-derived lncRNA TUC339 influences the progression of osteoarthritis by regulating synovial macrophage polarization and chondrocyte apoptosis.

Osteoarthritis (OA) is an extremely common type of chronic progressive disease in clinical practice. lncRNA TUC339 has a close association with bone marrow mesenchymal stem cell (BMSC) and an important impact on organismal inflammation. However, the mechanism of BMSC-derived lncRNA TUC339 on OA was poorly understood. In this study, we found that TUC339 was lower in the research group than in the control group and it was negatively correlated with IL-6, IL-8 and TNF-α. Prognosis TUC339 was lower in patients with recurrent OA than in those without recurrence, and ROC analysis manifested that TUC339 had a better predictive value for recurrence of OA. Phenotypic identification revealed elevated expression of CD29 and CD44 in BMSCs and TSG101, CD63 and CD81 in BMSCs-exosome (BMSCs-exo), with a stem cell versus exosome phenotype. Finally, animal experiments improved significantly in joint injury in the BMSCs-exo and TUC339-overexpression vector groups compared with control groups. Similarly, the activity of chondrocytes was enhanced, and apoptosis was reduced in the BMSCs-exo group versus the TUC339-overexpression vector group of rats. Study demonstrated that BMSCs-exo improves OA by elevating the expression of TUC339 to promote M1-type mø to M2-type polarization, suppressing inflammation and promoting chondrocyte activity, which provides a reliable basis for future transplantation therapy of MSCs for OA.

Bivalent Gadolinium Ions Forming Injectable Hydrogels for Simultaneous In Situ Vaccination Therapy and Imaging of Soft Tissue Sarcoma.

Doxorubicin (DOX) is the classic soft tissue sarcomas (STS) first-line treatment drug, while dose-dependent myelosuppression and cardiotoxicity limit its application in clinic. This research intends to apply DOX, which is also an inducer of immunogenic cell death as a part for "in situ vaccination" and conjointly uses PD-1 inhibitors to enhance antitumor efficacy. In order to achieve the sustained vaccination effect and real-time monitoring of distribution in vivo, the in situ forming and injectable hydrogel platform with the function of visualization is established for local delivery. The hydrogel platform is synthesized by hyaluronic acid-dopamine coordinated with gadolinium ions (Gd2+ ). Gd2+ provides the ability of magnetic resonance imaging, meanwhile further cross-linking the hydrogel network. Experiments show excellent ability of sustained release and imaging tracking for the hydrogel platform. In mouse STS models, the "in situ vaccination" hydrogels show the best effect of inhibiting tumor growth. Further analysis of tumor tissues show that "in situ vaccination" group can increase T cell infiltration, promote M1-type macrophage polarization and block elevated PD-1/PD-L1 pathway caused by DOX. These results are expected to prove the potential for synthesized hydrogels to achieve a universal platform for "in situ vaccination" strategies on STS treatments.

LncRNA TSIX aggravates spinal cord injury by regulating the PI3K/AKT pathway via the miR-532-3p/DDOST axis.

Long noncoding RNA (lncRNA)-X-inactive-specific transcript (TSIX) expression is upregulated in spinal cord tissues following spinal cord injury (SCI). However, the role of lncRNA-TSIX in SCI remains elusive. SCI animal model was established using C57BL/6 mice. LncRNA TSIX and miR-532-3p expression were determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Apoptosis, cell proliferation, and migration were evaluated by transferase dUTP nick end labeling staining, CCK-8, and Transwell assays, respectively. The interaction of miR-532-3p with lncRNA TSIX and DDOST was explored via a dual-luciferase reporter system. Hematoxylin-eosin staining and the Basso, Beattie, and Bresnahan locomotor rating (BBB) scale were performed to investigate SCI progression. The expression of the lncRNA TSIX was found to be significantly upregulated in the serum of SCI patients and spinal cord tissues of SCI mice. The overexpression of lncRNA TSIX enhanced spinal cord neural stem cell (SC-NSC) proliferation and migration in vitro while inhibiting apoptosis and inflammatory cell infiltration in vivo. Moreover, lncRNA TSIX acted as a molecular sponge for miR-532-3p, and the knockdown of miR-532-3p promoted proliferation and migration and inhibited apoptosis of SC-NSCs. Moreover, DDOST was found to be the downstream target of miR-532-3p, and DDOST overexpression showed a similar effect as miR-532-3p silencing on the proliferation, migration, and apoptosis of SC-NSCs. Furthermore, we found that lncRNA TSIX overexpression promoted the activation of the PI3K/AKT signaling pathway. LncRNA TSIX aggravates SCI by regulating the PI3K/AKT pathway via the miR-532-3p/DDOST axis, indicating potential applications for targeted therapy of SCI regeneration.

Air pollution and associated health impact and economic loss embodied in inter-provincial electricity transfer in China.

As the largest producer and consumer of coal in the world, China heavily relies on coal resources for thermal power generation. Owing to the unbalanced distribution of energy resources, electricity transfer among regions in China plays a key role in promoting economic growth and ensuring energy safety. However, little is known about air pollution and the related health impacts resulting from electricity transfer. This study assessed PM2.5 pollution and related health and economic losses attributable to the inter-provincial electricity transfer in mainland China in 2016. The results show that a large amount of virtual air pollutant emissions were transferred from energy-abundant northern, western and central China to well-developed and populated eastern coastal regions. Correspondingly, the inter-provincial electricity transfer dramatically reduced the atmospheric levels of PM2.5 and related health and economic losses in eastern and southern China, while increasing those in northern, western and central China. The health benefits attributable to inter-provincial electricity transfer were mainly found in Guangdong, Liaoning, Jiangsu and Shandong, whereas the extra health loss is concentrated in Hebei, Shanxi, Inner Mongolia, and Heilongjiang. Overall, the inter-provincial electricity transfer led to an extra increase of 3600 (95 % CI: 3200-4100) PM2.5-related deaths and 345 (95 % CI: 294-389) million USD of economic loss in China in 2016. The results could assist air pollution mitigation strategies for the thermal power sector in China by strengthening the cooperation between suppliers and consumers of electricity.

A New Time-Window Prediction Model For Traumatic Hemorrhagic Shock Based on Interpretable Machine Learning.

ABSTRACT: Early warning prediction of traumatic hemorrhagic shock (THS) can greatly reduce patient mortality and morbidity. We aimed to develop and validate models with different stepped feature sets to predict THS in advance. From the PLA General Hospital Emergency Rescue Database and Medical Information Mart for Intensive Care III, we identified 604 and 1,614 patients, respectively. Two popular machine learning algorithms (i.e., extreme gradient boosting [XGBoost] and logistic regression) were applied. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the performance of the models. By analyzing the feature importance based on XGBoost, we found that features in vital signs (VS), routine blood (RB), and blood gas analysis (BG) were the most relevant to THS (0.292, 0.249, and 0.225, respectively). Thus, the stepped relationships existing in them were revealed. Furthermore, the three stepped feature sets (i.e., VS, VS + RB, and VS + RB + sBG) were passed to the two machine learning algorithms to predict THS in the subsequent T hours (where T = 3, 2, 1, or 0.5), respectively. Results showed that the XGBoost model performance was significantly better than the logistic regression. The model using vital signs alone achieved good performance at the half-hour time window (AUROC = 0.935), and the performance was increased when laboratory results were added, especially when the time window was 1 h (AUROC = 0.950 and 0.968, respectively). These good-performing interpretable models demonstrated acceptable generalization ability in external validation, which could flexibly and rollingly predict THS T hours (where T = 0.5, 1) prior to clinical recognition. A prospective study is necessary to determine the clinical utility of the proposed THS prediction models.

An interpretable machine learning model based on a quick pre-screening system enables accurate deterioration risk prediction for COVID-19.

A high-performing interpretable model is proposed to predict the risk of deterioration in coronavirus disease 2019 (COVID-19) patients. The model was developed using a cohort of 3028 patients diagnosed with COVID-19 and exhibiting common clinical symptoms that were internally verified (AUC 0.8517, 95% CI 0.8433, 0.8601). A total of 15 high risk factors for deterioration and their approximate warning ranges were identified. This included prothrombin time (PT), prothrombin activity, lactate dehydrogenase, international normalized ratio, heart rate, body-mass index (BMI), D-dimer, creatine kinase, hematocrit, urine specific gravity, magnesium, globulin, activated partial thromboplastin time, lymphocyte count (L%), and platelet count. Four of these indicators (PT, heart rate, BMI, HCT) and comorbidities were selected for a streamlined combination of indicators to produce faster results. The resulting model showed good predictive performance (AUC 0.7941 95% CI 0.7926, 0.8151). A website for quick pre-screening online was also developed as part of the study.

GSK-3 mediates nuclear translocation of p62/SQSTM1 in MPTP-induced mouse model of Parkinson's disease.

p62/SQSTM1 is a multifunctional, cytoplasmic protein with fundamental roles in autophagy and antioxidant responses. Here we showed that p62 translocated from the cytoplasm to the nucleus in nigral dopaminergic neurons in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrid (MPTP)-induced mouse model of Parkinson's disease (PD). We found that p62 was physically associated with glycogen synthase kinase (GSK)-3ß, a serine/threonine protein kinase implicated in dopaminergic neurodegeneration in PD, and that MPTP treatment promoted dissociation of the complex in mice. Conditional knockout of GSK-3 prevented nuclear translocation of p62, suggesting that this translocation was detrimental to dopaminergic neurons. p62 knockout mice were used to investigate the role of p62 in MPTP-induced neuronal death. Knockout of p62 aggravated neuronal injury induced by MPTP intoxication, suggesting that p62 plays an important role in dopaminergic cell survival in stress conditions. Together, our data demonstrate that GSK-3 mediates nuclear translocation of p62 during MPTP-induced parkinsonian neurodegeneration. These findings shed new light on the role of the cytoplasmic-nuclear shuttling of p62 and the mechanism underlying GSK-3-depedent neuronal death in PD pathogenesis.

Long noncoding RNA ZFAS1 aggravates spinal cord injury by binding with miR-1953 and regulating the PTEN/PI3K/AKT pathway.

Multiple evidence has shown that long non-coding RNAs (lncRNAs) are novel modulators in the development of many neurological diseases, including spinal cord injury (SCI). Recently, a novel lncRNA zinc finger antisense 1 (ZFAS1) has been found to facilitate the development of many human diseases. However, the effect of ZFAS1 in SCI has not been explored. In the present study, we used the SCI mouse models and LPS-treated BV-2 cellular models to explore the role of ZFAS1 in SCI. Basso Mouse Scale score was applied to reveal locomotor function. Cresyl violet staining was used to reveal volume of spared myelin around the lesion in the injured cord. RIP and luciferase reporter assay were applied to detect binding capacity among RNAs. Next, ZFAS1 was identified to be upregulated in spinal cord tissues of SCI mice. ZFAS1 knockdown promoted functional recovery and inhibited cell apoptosis and the inflammatory response in SCI mice. ZFAS1 bound with microRNA 1953 (miR-1953), and miR-1953 was downregulated in spinal cord tissues of SCI mice. Furthermore, we confirmed that ZFAS1 promoted SCI progression via binding with miR-1953. In addition, phosphatase and tensin homolog (PTEN) was verified to be a downstream target for miR-1953 in vitro, and PTEN was upregulated in spinal cord tissues of SCI mice. Finally, we illustrated that ZFAS1 inactivated the PI3K/AKT pathway through upregulation of PTEN. In conclusion, our study revealed that ZFAS1 facilitated SCI by binding with miR-1953 and regulating the PTEN/PI3K/AKT pathway, which may provide a potential novel insight for treatment of SCI.

MiR-122-5p Mitigates Inflammation, Reactive Oxygen Species and SH-SY5Y Apoptosis by Targeting CPEB1 After Spinal Cord Injury Via the PI3K/AKT Signaling Pathway.

Spinal cord injury (SCI) is a threatening disease that lead to severe motor and sensory deficits. Previous research has revealed that miRNAs are involved in the pathogenesis of a variety of diseases. However, whether miR-122-5p was involved in SCI was rarely investigated. In our study, we intended to probe role of miR-122-5p in the regulation of inflammatory response, reactive oxygen species (ROS) and SH-SY5Y apoptosis. We found miR-122-5p was downregulated in SCI mouse model and LPS-induced SH-SY5Y cells. Moreover, miR-122-5p overexpression alleviated inflammatory response, ROS and SH-SY5Y apoptosis in SCI mice. In addition, miR-122-5p elevation also mitigated SCI in LPS-induced SH-SY5Y cells. Additionally, cytoplasmic polyadenylation element binding protein 1 (CPEB1) was verified to be a target of miR-122-5p. CPEB1 expression was upregulated in SCI mouse model and LPS-induced SH-SY5Y cells. CPEB1 expression was negatively related to miR-122-5p expression. Moreover, CPEB1 activated the PI3K/AKT signaling pathway in SH-SY5Y cells. Finally, CPEB1 elevation recovered the suppressive effect on inflammatory response, ROS and SH-SY5Y apoptosis in LPS-treated SH-SY5Y cells mediated by miR-122-5p upregulation and through the PI3K/AKT signaling pathway.

Alleviation of Cartilage Destruction by Sinapic Acid in Experimental Osteoarthritis.

Sinapic acid (SA) modulates the nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway in chondrocytes. In order to test the hypothesis that SA is protective against the development of osteoarthritis (OA), primary mouse chondrocytes were treated in vitro with SA and the promoter transactivation activity of heme oxygenase 1 (HO-1), nuclear translocation of Nrf2, and protein expression of HO-1 were assayed. To test the hypothesis in vivo, a destabilization of the medial meniscus (DMM) model was used to induce OA in the knees of mice and SA was delivered orally to the experimental group. The chondrocytes were harvested for further analysis. The expression of HO-1 was similarly upregulated in cartilage from both the experimental mice and human chondrocytes from osteoarthritic knees. SA was found to enhance the promoter transactivation activity of heme oxygenase 1 (HO-1) and increase the expression of Nrf2 and HO-1 in primary chondrocytes. Histopathologic scores showed that the damage induced by the DMM model was significantly lower in the SA treatment group. The addition of a HO-1 inhibitor with SA did not show additional benefit over SA alone in terms of cartilage degradation or histopathologic scores. The expression of TNF-α, IL-1ß, IL-6, MMP-1, MMP-3, MMP-13, ADAMTS4, and ADAMTS5 was significantly reduced both in vitro and in vivo by the presence of SA. Protein expressions of HO-1 and Nrf2 were substantially increased in knee cartilage of mice that received oral SA. Our results suggest that SA should be further explored as a preventative treatment for OA.

[Prediction and feature selection for fatal gastrointestinal bleeding recurrence in hospital via machine learning].

OBJECTIVE: To propose a method of prediction for fatal gastrointestinal bleeding recurrence in hospital and a method of feature selection via machine learning models. METHODS: 728 digestive tract hemorrhage samples were extracted from the first aid database of PLA General Hospital, and 343 patients among them were diagnosed as fatal gastrointestinal bleeding recurrence in hospital. A total of 64 physiological or laboratory indicators were extracted and screened. Based on the ten-fold cross-validation, Logistic regression, AdaBoost and XGBoost were used for classification prediction and comparison. XGBoost was used to search sequence features, and the key indicators for predicting fatal gastrointestinal bleeding recurrence in hospital were screened out according to the importance of the indicators during training. RESULTS: Logistic regression, AdaBoost and XGBoost all get better F1.5 score under each feature input dimension, among which XGBoost had the best effect and the highest score, which was able to identify as many patients as possible who might have fatal gastrointestinal bleeding recurrence in hospital. Through XGBoost iteration results, the Top 30 indicators with high importance for predicting fatal gastrointestinal bleeding recurrence in hospital were ranked. The F1.5 scores of the first 12 key indicators peaked at iteration (0.893), including hemoglobin (Hb), calcium (CA), red blood cell count (RBC), mean platelet volume (MPV), mean erythrocyte hemoglobin concentration (MCH), systolic blood pressure (SBP), platelet count (PLT), magnesium (MG), lymphocyte (LYM), glucose (GLU, blood gas analysis), glucose (GLU, blood biochemistry) and diastolic blood pressure (DBP). CONCLUSIONS: Logistic regression, AdaBoost and XGBoost could achieve the purpose of early warning for predicting fatal gastrointestinal bleeding recurrence in hospital, and XGBoost is the most suitable. The 12 most important indicators were screened out by sequential forward selection.

Combining Bone Marrow Stromal Cells with Green Tea Polyphenols Attenuates the Blood-Spinal Cord Barrier Permeability in Rats with Compression Spinal Cord Injury.

This study was performed to investigate the effect of bone marrow stromal cells (BMSCs) combined with green tea polyphenols (GTPs) on the blood-spinal cord barrier (BSCB) permeability after spinal cord injury (SCI) in the rat model. In the model of SCI rats, we found that the water content and the BSCB permeability were decreased by BMSCs and GTPs treatment, and their combination had a synergistic effect. Further, the motor function of rats was also greatly improved by BMSCs and GTPs administration. After treated by the combination of BMSCs and GTPs, SCI rats showed the up-regulated expression of tight junction (TJ) associated proteins claudin-5, occludin and ZO-1 by Western blot, which was more remarkable than that in the single treatment. The increased expression levels of claudin-5, occludin, and ZO-1 were the most obvious in the spinal cord microvessels using immunohistochemistry assay. This led to the conclusion that the combination of BMSCs and GTPs could decrease the BSCB permeability by up-regulating protein expression levels of claudin-5, occludin, and ZO-1. In addition, after BMSCs and GTPs administration, the results of Western blot and enzyme-linked immunosorbent assay (ELISA) revealed a significant decrease in protein expression level and the activation of nuclear factor-кB (NF-кB) p65. Our results indicated that combination of BMSCs and GTPs could improve motor function after SCI, which might be correlated with improvements in BSCB integrity, and that NF-кB might be involved in the modulating process.

A disintegrin and metalloprotease 17 promotes microglial cell survival via epidermal growth factor receptor signalling following spinal cord injury.

Tumour necrosis factor-α (TNF-α) converting enzyme (TACE), also termed a disintegrin and metalloprotease 17 (ADAM17), is involved in multiple cell signalling pathways. Through the secretion of epidermal growth factor receptor (EGFR) ligands, ADAM17 can activate the EGFR and is involved in various downstream signalling pathways. The present study aimed to investigate whether ADAM17­induced EGFR transactivation is involved in microglial cell survival following spinal cord injury (SCI). Reverse transcription quantitative polymerase chain reaction and western blot analysis revealed that ADAM17 was overexpressed in a mouse model following SCI. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay demonstrated that the viability of human microglia and oligodendrocytes were significantly reduced in a time- and dose-dependent manner following treatment with the ADAM17 antagonist, TNF protease inhibitor 2. Hoechst 33258 staining and flow cytometric analysis revealed that inhibiting ADAM17 increased the rate of cellular apoptosis in neuronal and glial cell cultures, which was accompanied by increased cleavage of caspase-3. Western blot analysis demonstrated that inhibiting ADAM17 resulted in a reduction in the phosphorylation of the EGFR signalling pathway components and thereby impaired functional recovery, inhibited cell viability and prompted microglial apoptosis following SCI. Pre-treatment with the EGFR inhibitor, AG1478, rescued the ADAM17­mediated proliferation of microglial cells. These data demonstrated that ADAM17 contributed to microglial cell survival, predominantly by EGFR signalling, following SCI.