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Background: Complete lymph node dissection (CLND) for patients with melanoma remains controversial. This meta-analysis aimed to compare the prognoses and complications between the CLND and control groups (patients who receive adjuvant treatment or observation only) in patients with sentinel lymph node (SLN)-positive melanoma. Methods: The PubMed, Embase, Cochrane, and Web of Science databases were searched for cohort studies and randomized clinical trials (RCTs) conducted between 1964 and 2022, and the quality of the studies was assessed using the Cochrane risk-of-bias tool and Newcastle-Ottawa Scale. Hazard ratios (HR) or risk ratios (RR) with 95% confidence intervals (CIs) were calculated for each outcome. Heterogeneity and sensitivity tests were also conducted, and publication bias tests were performed when the pooled number of studies was >10. Results: Fifteen studies, including 11 cohort studies and 4 RCTs, were enrolled and assessed for quality. Analysis of overall survival showed no significant difference between the CLND and control groups (HR=1.02, 95% CI: 0.69–1.51, P=0.922). Similarly, recurrence-free survival (HR=0.84, 95% CI: 0.6–1.16, P=0.287), disease-free survival (HR=1.06, 95% CI: 0.65–1.72, P=0.82), and disease-specific survival (HR=0.84, 95% CI: 0.59–1.21, P=0.355) showed no difference between the two groups. CLND did not reduce the risk of recurrence (RR=0.98, 95% CI: 0.8–1.2, P=0.851). Conclusion: Remarkably, patients who underwent CLND were more likely to have complications such as flap necrosis and lymphedema than the controls. CLND does not improve patient prognosis and may increase the incidence of complications.

Abstract Acral melanoma (AM) is a rare subtype of melanoma characterized by a high incidence of lymph node (LN) metastasis, a critical factor in tumor dissemination and therapeutic decision-making. Here, we employ single-cell and spatial transcriptomic analyses to investigate the dynamic evolution of early AM dissemination. Our findings reveal substantial inter- and intra-tumor heterogeneity in AM, alongside a highly immunosuppressive tumor microenvironment and complex intercellular communication networks, particularly in patients with LN metastasis. Notably, we identify a strong association between MYC + Melanoma (MYC +MEL) and FGFBP2 +NKT cells with LN metastasis. Furthermore, we demonstrate that LN metastasis requires a metabolic shift towards fatty acid oxidation (FAO) induced by MITF in MYC +MEL cells. Etomoxir, a clinically approved FAO inhibitor, can effectively suppress MITF-mediated LN metastasis. This comprehensive dataset enhances our understanding of LN metastasis in AM, and provides insights into the potential therapeutic targeting for the management of early AM dissemination.

Refractory heart failure (RHF), or end-stage heart failure, has a poor prognosis and high case fatality rate, making it one of the therapeutic difficulties in the cardiovascular field. Despite the continuous abundance of methods and means for treating RHF in modern medicine, it still cannot meet the clinical needs of patients with RHF. How to further reduce the mortality rate and readmission rate of patients with RHF and improve their quality of life is still a difficult point in current research. In China, traditional Chinese medicine (TCM) has been widely used and has accumulated rich experience in the treatment of RHF due to its unique efficacy and safety advantages. Based on this, we comprehensively summarized and analyzed the clinical evidence and mechanism of action of TCM in the treatment of RHF and proposed urgent scientific issues and future research strategies for the treatment of RHF with TCM, to provide reference for the treatment of RHF.

Abstract Radiotherapy (RT) can induce tumor regression outside the irradiation field, known as the abscopal effect. However, the detailed underlying mechanisms remain largely unknown. A tumor‐bearing mouse model is successfully constructed by inducing both subcutaneous tumors and lung metastases. Single‐cell RNA sequencing, immunofluorescence, and flow cytometry are performed to explore the regulation of tumor microenvironment (TME) by RT. A series of in vitro assays, including luciferase reporter, RNA Pulldown, and fluorescent in situ hybridization (FISH) assays, are performed to evaluate the detailed mechanism of the abscopal effect. In addition, in vivo assays are performed to investigate combination therapy strategies for enhancing the abscopal effect. The results showed that RT significantly inhibited localized tumor and lung metastasis progression and improved the TME. Mechanistically, RT promoted the release of tumor‐derived exosomes carrying circPIK3R3, which is taken up by macrophages. circPIK3R3 promoted Type I interferon (I‐IFN) secretion and M1 polarization via the miR‐872‐3p/IRF7 axis. Secreted I‐IFN activated the JAK/STAT signaling pathway in CD8+ T cells, and promoted IFN‐γ and GZMB secretion. Together, the study shows that tumor‐derived exosomes promote I‐IFN secretion via the circPIK3R3/miR‐872‐3p/IRF7 axis in macrophages and enhance the anti‐tumor immune response of CD8+ T cells.

Abstract Post-COVID-19 pulmonary sequalae are well-recognized early in the pandemic. Survivorship clinics are crucial for managing at-risk patients. However, it is unclear who requires pulmonary function test (PFT) and when PFTs should be performed. We aim to investigate for whom and how these interval PFTs should be performed. We performed a single-centre, prospective cohort study on COVID-19 survivors between 1st May 2020 and 31st April 2022. These patients were followed up at 6, 9 and 12 months with interval PFT and Short Form-36 (SF-36) Health Survey. Those with PFT defects were offered a computed tomography scan of the thorax. Of the 46 patients recruited, 17 (37%) had severe/critical illness. Compared to those with mild/moderate disease, these patients were more likely to experience DLCO defects (59% versus 17%, p = 0.005) and had lower SF-36 scores (mean physical component summary score of 45 ± 12 versus 52 ± 8, p = 0.046). These differences were most notable at 6 months, compared to the 9- and 12-months intervals. DLCO defects were also associated with older age, raised inflammatory markers and extensive CXR infiltrates. Besides interstitial-like abnormalities, obesity and undiagnosed lung conditions accounted for 39% of the PFT abnormalities. Interval PFTs can be performed earliest 6 months post-COVID-19. Patients with normal tests were unlikely to develop new abnormalities and would not require repeat PFTs. Abnormal PFTs can be followed-up with repeat PFTs 6 monthly until resolution. Non-COVID-19 differentials should be considered for persistent PFT abnormalities.

Highlights The dual-ion co-regulation system shortens ion migration pathways, which endow the yarn muscle with high contractile stroke (34.7%) and contractile rate (9.4% s−1), more than twice that of the “rocking-chair” -type ion migration yarn muscles. The yarn muscle shows high isometric stress of 18.4 MPa (61 times that of skeletal muscles) and 8 times the isometric stress of the “rocking-chair” -type yarn muscles at a higher frequency. The intercalation reaction between $${\text{PF}}_{6}^{ - }$$ PF 6 - and collapsed carbon nanotubes allows the yarn muscle to achieve an energy-free high-tension catch state

Background: Continuous light exposure increases sympathetic excitation in rats, leading to hypertension, left ventricular hypertrophy, and fibrosis. This study was aimed to investigate whether continuous light exposure causes destabilization of vital signs and gut microbiota (GM) in Sprague Dawley (SD) rats and whether clonidine hydrochloride (CH), a central sympathetic depressant drug, could prevent these changes. Methods: Eight-week-old male SD rats were divided into three groups with different interventions for 14 weeks: control group (CG), 2-mL pure water gavaged daily while on a normal 12-h light/dark cycle; continuous illumination group (CI), 2-mL pure water gavaged daily while receiving continuous exposure to light (300 lx); and drug administration group (DA), CH (10 μg/kg) gavaged daily while receiving continuous exposure to light (300 lx). Results: The results showed that blood pressure, heart rate, and body weight were significantly higher in the CI group than in the CG and DA groups (P Prevotella (genus level) > Prevotellaceae_bacterium (species level) were enriched in the CI group. The Muribaculaceae family was more abundant in the CG group than in the CI group. Conclusion: Sympathetic nerve inhibition restored the abnormal vital signs and GM changes under continuous light exposure.

ABSTRACTArtificial muscle fibers driven electrothermally with excellent properties of response, stroke, and work capacity are expected to serve in some intelligent structures and systems. However, muscle fibers that operate in subzero environments are highly needed in industrial production and aerospace applications but remain challenging. Herein, we reported a coaxial artificial muscle fiber by electrospinning a sheath of polycaprolactone (PCL) nanofibers on the surface of a carbon nanotube (CNT) fiber core, achieving the actuation in response to thermal at subzero temperatures. The CNT@PCL coaxial muscle fiber under 0.3 MPa achieved a maximum contractile stroke of ~18% as the temperature changed from −130°C to 45°C. The actuation mechanism at subzero temperatures of this muscle fiber was analyzed in combination with the temperature-deformation schematic curve of different polymers. Furthermore, a temperature sensor based on this muscle fiber was developed, due to the excellent linear relationship between the contraction and temperature. A 3D-printed prosthetic arm was designed to further exhibit the application demonstrations of this muscle fiber in subzero environments. This work provides new insights into artificial muscle fibers for serving in extreme environments with ultralow temperatures.

Ischemia-reperfusion injury (IRI) is a complex phenomenon. Although researchers have long been aware of IRI, its complex signaling events and potential therapeutic targets are still an active research area. The role of reactive oxygen species in IRI has garnered great interest among scientists. Recent studies have found that reactive oxygen species produced by IRI can activate redox-sensitive transient receptor potential channels (redox TRPs). The discovery of redox TRPs provides a new perspective for understanding the mechanism of IRI.

BackgroundThe causal link between Type 2 diabetes (T2D) and coronary atherosclerosis has been established through wet lab experiments; however, its analysis with Genome-wide association studies (GWAS) data remains unexplored. This study aims to validate this relationship using Mendelian randomization analysis and explore the potential mediation of VLDL in this mechanism.MethodsEmploying Mendelian randomization analysis, we investigated the causal connection between T2D and coronary atherosclerosis. We utilized GWAS summary statistics from European ancestry cohorts, comprising 23,363 coronary atherosclerosis patients and 195,429 controls, along with 32,469 T2D patients and 183,185 controls. VLDL levels, linked to SNPs, were considered as a potential mediating causal factor that might contribute to coronary atherosclerosis in the presence of T2D. We employed the inverse variance weighted (IVW), Egger regression (MR-Egger), weighted median, and weighted model methods for causal effect estimation. A leave-one-out sensitivity analysis was conducted to ensure robustness.ResultsOur Mendelian randomization analysis demonstrated a genetic association between T2D and an increased coronary atherosclerosis risk, with the IVW estimate at 1.13 [95% confidence interval (CI): 1.07–1.20]. Additionally, we observed a suggestive causal link between T2D and VLDL levels, as evidenced by the IVW estimate of 1.02 (95% CI: 0.98–1.07). Further supporting lipid involvement in coronary atherosclerosis pathogenesis, the IVW-Egger estimate was 1.30 (95% CI: 1.06–1.58).ConclusionIn conclusion, this study highlights the autonomous contributions of T2D and VLDL levels to coronary atherosclerosis development. T2D is linked to a 13.35% elevated risk of coronary atherosclerosis, and within T2D patients, VLDL concentration rises by 2.49%. Notably, each standard deviation increase in VLDL raises the likelihood of heart disease by 29.6%. This underscores the significant role of lipid regulation, particularly VLDL, as a mediating pathway in coronary atherosclerosis progression.

Ship detection in synthetic aperture radar (SAR) images has gained great attention in civil and military fields. Anchor-based detection algorithms usually rely on preset candidate boxes, and a large amount of anchor boxes with different sizes will result in a large amount of computing resources being consumed. Recently, anchor-free algorithms have found wide applications in ship detection from SAR images. However, there are still some problems which limit the ship detection performance to a certain extent, such as how to effectively fuse salient features and unbalanced distribution of positive samples. In order to tackle the above problems, we propose a novel anchor-free model named salient feature fusion (SFF)–YOLOX with SFF mechanism. First, we redesign the network of YOLOX to obtain the best balance between detection accuracy and running speed. Second, a saliency region extraction module is introduced to generate the corresponding salient guide map of the input image. Besides, the SFF mechanism is proposed by fusing deep features and salient features to better enhance the discrimination of the multiscale targets. Finally, we improve the SimOTA mechanism by combining the predicted intersection over union (IoUs) and the anchor IoUs to the ground truth bounding boxes to instruct label assignment. We evaluate the detection accuracy and running speed of SFF–YOLOX on the public dataset single shot detector and test the generalization ability on HRSID and two complex large-scale SAR images, and the experimental results prove the model's effectiveness for ship detection task in SAR images.

Abstract Background Studies of aberrantly expressed circular RNAs (circRNAs) can provide insights into the molecular mechanisms of osteosarcoma (OS). However, the role of circ_0001174 in OS progression remains unknown. This study is aimed to identify differentially expressed circRNAs and messenger RNAs (mRNAs) in patients with OS and to investigate potential regulatory ways of circ_0001174. Methods High-throughput sequencing was performed to screen aberrantly expressed circRNAs and mRNAs between tumor and paracancerous tissues from patients with OS. Several bioinformatics tools were used to analyze the functions and pathways of the differentially expressed genes between the tissues. Cell counting kit-8, cell migration and invasion assays were performed to evaluate the functions of the critical circRNAs. RNA interference experiments, quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting were used to explore the relationship between miR-186-5p and circ_0001174 or metastasis-associated in colon cancer 1 (MACC1). Results Compared with the paracancerous tissues, 109 circRNAs and 1264 mRNAs were differentially expressed in the OS tissues, including 88 circRNAs and 707 mRNAs that were upregulated and 21 circRNAs and 557 mRNAs that were downregulated. The expression of four upregulated and four downregulated circRNAs was validated using RT-qPCR; the results were consistent with the sequencing data, and circ_0001174 was found to be significantly upregulated in 16 pairs of OS tissues and OS cell lines (fold change > 2.0, P value

Calcium (Ca2+) plays a critical role in podocyte function. The Ca2+-sensitive receptors on the cell surface can sense changes in Ca2+ concentration, and Ca2+ flow into podocytes, after activation of Ca2+ channels (such as transient receptor potential canonical (TRPC) channels and N-type calcium channels) by different stimuli. In addition, the type 2 ryanodine receptor (RyR2) and the voltage-dependent anion channel 1 (VDAC1) on mitochondrial store-operated calcium channels (SOCs) on the endoplasmic reticulum maintain the Ca2+ homeostasis of the organelle. Ca2+ signaling is transmitted through multiple downstream signaling pathways and participates in the morphogenesis, structural maintenance, and survival of podocytes. When Ca2+ is dysregulated, it leads to the occurrence and progression of various diseases, such as focal segmental glomerulosclerosis, diabetic kidney disease, lupus nephritis, transplant glomerulopathy, and hypertensive renal injury. Ca2+ signaling is a promising therapeutic target for podocyte-related diseases. This review first summarizes the role of Ca2+ sensing, Ca2+ channels, and different Ca2+-signaling pathways in the biological functions of podocytes, then, explores the status of Ca2+ signaling in different podocyte-related diseases and its advances as a therapeutic target.

Ship detection in synthetic aperture radar (SAR) images is an important and challenging work in the field of image processing. Traditional detection algorithms usually rely on handmade features or predefined thresholds, the different performance is obtained with varying degrees of prior knowledge, and it is difficult to take advantage of big data. Recently, deep learning algorithms have found wide applications in ship detection from SAR images. However, due to the complex backgrounds and multiscale ships, it is hard for deep networks to extract representative target features, which limits the ship detection performance to a certain extent. In order to tackle the above problems, we propose an improved YOLOv4 (ImYOLOv4) based on attention mechanism. Firstly, to achieve the best trade-off between detection accuracy and speed, we adopt the off-the-shelf YOLOv4 as our basic framework because of its fast detection speed. Secondly, a thresholding attention module (TAM) is introduced to suppress the adverse effect of complex backgrounds and noises. Besides, we embed channel attention module (CAM) into improved BiFPN as the feature pyramid network (FPN) to better enhance the discrimination of the multiscale target features. Finally, the decoupled head with two parallel branches improves the performance of classification and regression. The proposed method is evaluated on public SAR dataset and the experimental results demonstrate that it has higher efficiency and feasibility than other mainstream methods, yielding the accuracy of 94.16% at intersection over union of 0.5 and 58.19% at intersection over union of 0.75.

Abstract The prevalence of coronary artery disease (CAD) in Tibetan Highlanders is lower than that in plain-living individuals, but the mechanism still unclear. Gut microbiota (GM) disorder is considered one of the potential factors involved in the pathogenesis of CAD, but the GM characteristics of Tibetan Highlanders suffering from CAD are unknown. We sequenced the V3-V4 region of the 16S ribosomal RNA of gut bacteria from fecal samples from Tibetan and Han CAD patients and healthy individuals inhabiting the Qinghai-Tibet Plateau, as well as from Han CAD patients and healthy individuals living at sea level, and we analyzed the GM characteristics of these subjects by bioinformatics analysis. The results showed that Tibetan Highlanders suffering from CAD had higher GM α-diversity, with differently distributed cluster compared with healthy Tibetan Highlanders and Han CAD patients living at high and low altitudes. Genera Catenibacterium, Clostridium_sensu_stricto, Holdemanella, and Ruminococcus 2 were enriched in Tibetan Highlanders suffering from CAD compared with healthy Tibetan Highlanders and Han CAD patients living at high- and low-altitudes. Prevotella was enriched in Tibetan Highlanders suffering from CAD compared with Han CAD patients living at high- and low-altitudes. Moreover, Catenibacterium was positively correlated with Prevotella. Additionally, Catenibacterium, Holdemanella, and Prevotella were positively correlated with fermented dairy product, carbohydrate and fiber intake by the subjects, while Clostridium_sensu_stricto was negatively correlated with protein intake by the subjects. In conclusion, our study indicated that Tibetan Highlanders suffering from CAD showed distinct GM, which was linked to their unique dietary characteristics and might associated with CAD.

BackgroundAs a novel immune checkpoint, CD73 has been reported to play prominent roles in several malignancies. However, the significance of CD73 in melanoma remains ambiguous. This study sought to reveal the impact of CD73 on the tumor microenvironment (TME) and patients’ prognosis, and to investigate whether CD73 could be a therapeutic target in Chinese melanomas, which were dominated by acral and mucosal subtypes.MethodsTwo independent Chinese cohorts of 194 patients with melanoma were enrolled. CD73 and PD-L1 expression as well as CD8+ and CD56+ cell infiltrations were evaluated by immunohistochemistry in 194 resected melanoma samples. Clinical outcomes of patients were assessed utilizing the Kaplan-Meier plotter and Cox proportional hazard analysis. RNA-seq data was obtained from TCGA database. Gene set functional annotations were performed based on GO, KEGG and GSEA analysis. CIBERSORT, ssGSEA and TIMER were used to explore the association between CD73 and immune infiltration. These findings were validated by establishing tumor xenograft model, and functions of tumor-infiltrating immune cells were examined by flow cytometry and immunofluorescence.ResultsHigh CD73 expression showed poorer clinical outcomes and was identified as an independent prognostic indicator for survival in two cohorts. Expression of CD73 was more prevalent than PD-L1 in Chinese melanoma cohorts (54.6% vs 23.2%). Co-expression of both immune checkpoints was infrequent (12.9%) in melanoma, and 54.4% of PD-L1 negative cases showed elevated expression of CD73. CD73high tumors showed a microenvironment with fewer CD8+ T cells and CD56+ NK cells infiltration, which displayed a dysfunctional phenotype. With the treatment of CD73 inhibitor APCP, the amount of CD8+ T cells and CD56+ NK cells infiltrated in tumors was elevated and the immunosuppressive effect of CD73 was eliminated.ConclusionsHigh CD73 expression was associated with an inhibitory TME and adverse clinical outcomes of melanoma. In comparison to PD-L1, CD73 was more prevalent and possessed more definite prognostic significance. Therefore, it may serve as a prognostic indicator and immunotherapeutic target next to PD-L1 in melanoma for Chinese population.

Abstract As a non‐contact temperature distribution measurement method, infrared thermography (IRT) has emerged as an indispensable tool in condition monitoring and fault diagnosis of electrical equipment based on the absolute and relative temperature values. Manual fault inspection, as an expert‐experiences based evaluation method, has formed a mature technical scheme with a large number of application cases. However, the efficiency and accuracy of manual fault inspection are being challenged by the rapid growth in the number of equipment in power grid. The situation is improving with the advanced of image processing technique. Machine‐assisted fault diagnosis provides a novel method to assist human beings to complete fault diagnosis under the intervention of human prior knowledge. However, the limitations of infrared images bring challenges to image analysis processing especially target detection. In pursuit of automatic fault diagnosis, deep learning algorithms are introduced to achieve target detection in the complex environment. This study reviews the development of IRT‐based diagnostics beginning with the general procedures, objects, and limitations of IRT‐based fault inspection, and then gives an insight into the popular machine‐assisted fault diagnosis as well as image‐based intelligent fault identification. In addition, the future recommendations of IRT are also provided from construction of intelligent infrared detection system, establishment of an open and shared infrared image database and comprehensive utilization of joint visualization diagnosis technology.

Background: Xin-Su-Ning Capsules (XSNC) is an effective prescription for the treatment of arrhythmia composed of eleven Chinese herbs. With the wide application of XSNC in clinic, its quality control issues have also received increasing attention. Based on the multi-components characteristics of Chinese herbal compound, there is an urgent need to establish a quality evaluation system. Methods: Gas chromatography-mass spectrometry (GC-MS) and ultra high-performance liquid chromatography quadrupole electrostatic orbitrap high resolution mass spectrometry (UHPLC-Q-Exactive-Orbitrap-MS) were performed to identify the preliminary chemical profile of XSNC. Subsequently, a rapid ultra high-performance liquid chromatography coupled with electrospray ionization triple-quadrupole mass spectrometry (UHPLC-QQQ-MS/MS) method was developed to evaluate the quality of XSNC through a simultaneous determination of 16 components. Results: A total of 21 volatile components and 59 non-volatile compounds were tentatively identified from the XSNC, each identified compound is marked on the corresponding chromatogram. Moreover, sixteen chemical constituents (sophocarpine, matrine, febrifugine, berberine, palmatine, Tangeratin, nobiletin, liensinine, neferine, scopoletin, isoliquiritigenin, liquiritigenin, naringenin, naringin, hesperidin and glycyrrhizic acid) were quantified by the developed UHPLC-QQQ-MS/MS method. The method validation of the sixteen compounds was performed with acceptable linearity (R2, 0.9990-1.0000), precision (RSD, 0.25-2.06%), repeatability (RSD, 0.93-2.90%) and recovery (99.65%-104.03%, RSD≤4.35%). Conclusions: This qualitative analysis method sensitive and reliable for searching the volatile and non-volatile compounds from XSNC. The linearity, accuracy and precision of the quantitative analysis method were satisfactory. It is proposed that the methods described here can be applied for rapid evaluation, quality control and authenticity establishment of XSNC.

ABSTRACT: Objective: To identify novel biomarkers and therapeutic targets for primary melanoma using network-based microarray data analysis. Methods: Eligible microarray datasets from the Gene Expression Omnibus (GEO) database were used to identify differentially expressed genes (DEGs). The protein-protein interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to identify hub genes and pathways that might affect the survival of melanoma patients. Immunohistochemistry results obtained from the Human Protein Atlas (HPA) database confirmed the protein expression levels of hub genes. The Cancer Genome Atlas (TCGA) database was used to further verify the gene expression levels and conduct survival analysis. Results: Three microarray datasets (GSE3189, GSE15605, and GSE46517) containing 122 melanoma and 30 normal skin tissue samples were included. A total of 262 common differentially expressed genes (cDEGs) were identified based on three statistical approaches (Fisher's method, the random effects model (REM), and vote counting) with strict criteria. Of these, two upregulated genes, centromere protein F (CENPF) and pituitary tumor-transforming gene 1 (PTTG1), were selected as hub genes. HPA and TCGA database analyses confirmed that CENPF and PTTG1 were overexpressed in melanoma. Survival analysis showed that high expression levels of CENPF were significantly correlated with decreased overall survival (OS) (P=0.028). Conclusion: The expression level of CENPF was significantly upregulated in melanoma and correlated with decreased OS. Thus, CENPF may represent a novel biomarker and therapeutic target for melanoma patients.

Osteoporosis-derived bone marrow mesenchymal stem cells (OP-BMSCs) have impaired cell function, low osteogenic activity, and potential osteoclast inducibility, resulting in insufficient osseointegration and increased risk of catastrophic postoperative complications after arthroplasty. The low autophagy activity of OP-BMSCs contributed to poor osseointegration, which could be regulated by the classical autophagic activator, rapamycin. Hence, it is of great significance to regulate autophagy by rapamycin to promote osseointegration at the three-dimensional (3D) printed prosthetic interfaces under osteoporotic environment. In this study, 3D printed porous titanium alloy prosthetic interfaces with bionic pore size and porosity were prepared and implanted into the distal femur of osteoporosis rabbits. Subsequently, a transdermal drug delivery device was used to deliver rapamycin to the interfaces implantation sites. Ultrasound-mediated rapamycin delivery could restore the declined cellular activities (including cell viability, proliferation, migration, and osteogenesis), as well as inhibit potential osteoclast-inducing capacity and adipogenic differentiation by upregulating the autophagy level of OP-BMSCs. Moreover, percutaneous ultrasound-mediated rapamycin delivery significantly improved bone ingrowth and osseointegration of prosthetic interfaces in osteoporotic environment. To conclude, this novel therapy combining 3D printed bionic prosthesis and percutaneous ultrasound-mediated rapamycin delivery can effectively promote prosthetic interfaces osseointegration by regulating autophagy after arthroplasty for patients with osteoporosis.

Abstract In this paper, we apply a reliable combination of maximum modulus method with respect to the Schrödinger operator and Phragmén–Lindelöf method to investigate nonlinear conservation laws for the Schrödinger boundary value problems of second order. As an application, we prove the global existence to the solution for the Cauchy problem of the semilinear Schrödinger equation. The results reveal that this method is effective and simple.

Background and purposeCaV1.2 channels contribute to action potential upstroke in pacemaker cells, plateau potential in working myocytes, and initiate excitation-contraction coupling. Understanding drug action on CaV1.2 channels may inform potential impact on cardiac function. However, literature shows large degrees of variability between CaV1.2 pharmacology generated by different laboratories, casting doubt regarding the utility of these data to predict or interpret clinical outcomes. This study examined experimental factors that may impact CaV1.2 pharmacology.Experimental approachWhole cell recordings were made on CaV1.2 overexpression cells. Current was evoked using a "step-step-ramp" waveform that elicited a step and a ramp current. Experimental factors examined were: 1) near physiological vs. room temperature for recording, 2) drug inhibition of the step vs. the ramp current, and 3) Ca2+ vs. Ba2+ as the charge carrier. Eight drugs were studied.Key resultsCaV1.2 current exhibited prominent rundown, exquisite temperature sensitivity, and required a high degree of series resistance compensation to optimize voltage control. Temperature-dependent effects were examined for verapamil and methadone. Verapamil's block potency shifted by up to 4X between room to near physiological temperature. Methadone exhibited facilitatory and inhibitory effects at near physiological temperature, and only inhibitory effect at room temperature. Most drugs inhibited the ramp current more potently than the step current-a preference enhanced when Ba2+ was the charge carrier. The slopes of the concentration-inhibition relationships for many drugs were shallow, temperature-dependent, and differed between the step and the ramp current.Conclusions and implicationsAll experimental factors examined affected CaV1.2 pharmacology. In addition, whole cell CaV1.2 current characteristics-rundown, temperature sensitivity, and impact of series resistance-are also factors that can impact pharmacology. Drug effects on CaV1.2 channels appear more complex than simple pore block mechanism. Normalizing laboratory-specific approaches is key to improve inter-laboratory data reproducibility. Releasing original electrophysiology records is essential to promote transparency and enable the independent evaluation of data quality.

In this paper, the statistical characteristics of the multi-cascade κ-μ shadowed fading channels are investigated and analyzed under the classic Wyner’s eavesdropping model. In particular, the general accurate expressions of the probability density function and the cumulative distribution function for amplitude and signal-to-noise ratio (SNR) are derived for the first time. Moreover, we further utilize the two performance evaluation metrics including outage probability and intercept probability to investigate the impacts of cascade number and channel parameters on reliability and security. Finally, the theoretical results are consistent with the simulations, proving the correctness of the derivation. The interesting conclusion is that when the average SNR is greater than 2 dB, the reliability of the multi-cascade model will decrease as the number of cascade increases; on the contrary, more cascading can lead to stronger anti-eavesdropping ability.

Although there have been remarkable advances in cartilage tissue engineering, construction of irregularly shaped cartilage, including auricular, nasal, tracheal, and meniscus cartilages, remains challenging because of the difficulty in reproducing its precise structure and specific function. Among the advanced fabrication methods, three-dimensional (3D) printing technology offers great potential for achieving shape imitation and bionic performance in cartilage tissue engineering. This review discusses requirements for 3D printing of various irregularly shaped cartilage tissues, as well as selection of appropriate printing materials and seed cells. Current advances in 3D printing of irregularly shaped cartilage are also highlighted. Finally, developments in various types of cartilage tissue are described. This review is intended to provide guidance for future research in tissue engineering of irregularly shaped cartilage.

The healing of diabetic foot ulcers (DFUs) is a major challenge for clinical treatment because of the hyperglycemic and acidic microenvironment in the wound area. In this study, a self-healing, injectable, and pH-responsive hydrogel was synthesized by N-carboxyethyl chitosan (N-chitosan), hyaluronic acid–aldehyde (HA-ALD), adipic acid dihydrazide (ADH) through the formation of the reversible dynamic bonds, acylhydrazone and imine bonds. The presence of the acylhydrazone bond characterizes the hydrogel pH-responsive property. In this study, the insulin glargine was successfully incorporated into the hydrogel, allowing its sustained and pH-responsive releasing from the hydrogel for up to 14 days. The hydrogel presented good compatibility and pore structure, and the insulin released from the hydrogel maintained its original bioactivity. Full thickness wounds were established on the feet of diabetic rats to evaluate the therapeutic effect of the dressing. The results revealed that the bioactive insulin-loaded hydrogel dressing shortened the inflammatory phase, enhanced granulation tissue formation, promoted collagen deposition, accelerated re-epithelialization and neovascularization, and postponed or even improved peripheral neuropathy, thus, significantly accelerated DFUs healing. Our findings showed that the insulin-loaded hydrogels had promising potential as a multifunctional bioactive wound dressing for enhancing DFUs healing.

Osteoporosis is an age-related metabolic disease that results in limited bone regeneration capacity and excessive osteoclast activity. After arthroplasty in patients with osteoporosis, poor interface osseointegration resulting from insufficient bone regeneration ability often leads to catastrophic complications such as prosthesis displacement and loosening and periprosthetic fractures. In this study, we prepared a thermosensitive hydrogel loaded with bone morphogenetic protein-2 (BMP-2) to promote osteogenesis and osteoprotegerin (OPG) to inhibit excessive osteoclast activity. To construct three-dimensional (3D)-printed composite scaffolds for implantation, a hydrogel loaded with drugs was injected into porous Ti6Al4V scaffolds. The 3D-printed composite scaffolds showed good biocompatibility and sustained release of BMP-2 and OPG for more than 20 days. In vitro experiments indicated that composite scaffolds promoted osteogenic differentiation and reduced the osteoclastic activation simultaneously. Remarkably, immunofluorescence staining, micro-CT, histological, and biomechanical tests demonstrated that the sustained release of both BMP-2 and OPG from composite scaffolds significantly improved bone ingrowth and osseointegration in osteoporotic defects. In conclusion, this study demonstrated that the BMP-2- and OPG-loaded 3D-printed composite scaffolds can potentially promote osseointegration for osteoporotic patients after joint replacement.

Abstract Background Alzheimer's disease (AD) is the most common degenerative disease characterized by cognitive impairment, memory decline, and language disorder for which there is no effective treatment. Neurogenesis has been indicated in AD and may play an important role in the pathogenesis of AD. Targeting this pathway is a new idea for the treatment of the disease. A recent study reveals that the cellular prion protein (PrP), a receptor for Aβ oligomers, regulates neurogenesis, and its elevated expression is related to cell differentiation. The aim of the present study was to investigate the neuroprotective effects of 6D11 (PrP monoclonal antibody) via neurogenesis promotion in APP/PS1 transgenic mice and Aβ‐induced cell model of AD. Methods In the present study, 9‐month‐old male APP/PS1 mice were injected with 6D11. Then, the Morris water maze was used to examine the spatial learning and memory abilities of the mice in both groups, and immunostained was used to assess the level of Aβ, neurogenesis, and neural stem cells (NSCs) differentiation. Results 6D11 attenuated cognitive deficits in APP/PS1 transgenic mice, which was accompanied by a decrease of the deposition of Aβ. In addition, 6D11 treatment promoted differentiation of the existing hippocampal cells to neurons. Conclusions Our findings confirmed that 6D11 has a therapeutic effect in APP/PS1 transgenic AD mouse model and Aβ‐induced AD cell model, and the effect exerted via increase of neurogenesis and cell differentiation by transduction of Aβ peptide signal.

Background: Parasellar chondrosarcomas are extremely rare. This study describes the characteristics of parasellar chondrosarcoma and analyzes the risk factors and prognosis based on the resection degree. Methods: Fifteen patients with pathologically diagnosed parasellar chondrosarcoma were retrospectively analyzed for the clinical data, surgical methods, and prognosis to identify relationships between the surgical resection degree, tumor recurrence, and imaging characteristics. Results: Twelve patients had eye dysfunction and ptosis. Differentiation from other parasellar tumors by imaging is difficult. The preoperative Karnofsky Performance Scale (KPS) score positively correlated with the tumor resection degree (p = 0.026) and negatively correlated with the maximum tumor diameter (p = 0.001). Tumor recurrence negatively correlated with the resection degree (p = 0.009). The postoperative KPS score positively correlated with the preoperative KPS score (p < 0.001) and tumor resection degree (p = 0.026), and negatively correlated with the maximum tumor diameter (p = 0.016) and age (p = 0.047). An improved KPS score positively correlated with the tumor resection degree (p = 0.039). Patients who underwent total resection of the chondrosarcoma had longer progression-free survival than those who underwent partial resection (p = 0.0322). Conclusion: Parasellar chondrosarcomas are difficult to resect completely. Preoperative KPS score is an important factor for the degree of resection. KPS score, age, maximum tumor diameter, and resection degree may be important prognostic factors.

The growth plate (GP) is a cartilaginous region situated between the epiphysis and metaphysis at the end of the immature long bone, which is susceptible to mechanical damage because of its vulnerable structure. Due to the limited regeneration ability of the GP, current clinical treatment strategies (e.g., bone bridge resection and fat engraftment) always result in bone bridge formation, which will cause length discrepancy and angular deformity, thus making satisfactory outcomes difficult to achieve. The introduction of cartilage repair theory and cartilage tissue engineering technology may encourage novel therapeutic approaches for GP repair using tissue engineered GPs, including biocompatible scaffolds incorporated with appropriate seed cells and growth factors. In this review, we summarize the physiological structure of GPs, the pathological process, and repair phases of GP injuries, placing greater emphasis on advanced tissue engineering strategies for GP repair. Furthermore, we also propose that three-dimensional printing technology will play a significant role in this field in the future given its advantage of bionic replication of complex structures. We predict that tissue engineering strategies will offer a significant alternative to the management of GP injuries.

Combinations of biomaterials and cells can effectively target delivery of cells or other therapeutic factors to the brain to rebuild damaged nerve pathways after brain injury. Porous collagen-chitosan scaffolds were prepared by a freeze-drying method based on brain tissue engineering. The scaffolds were impregnated with rat bone marrow mesenchymal stem cells. A traumatic brain injury rat model was established using the 300 g weight free fall impact method. Bone marrow mesenchymal stem cells/collagen-chitosan scaffolds were implanted into the injured brain. Modified neurological severity scores were used to assess the recovery of neurological function. The Morris water maze was employed to determine spatial learning and memory abilities. Hematoxylin-eosin staining was performed to measure pathological changes in brain tissue. Immunohistochemistry was performed for vascular endothelial growth factor and for 5-bromo-2-deoxyuridine (BrdU)/neuron specific enolase and BrdU/glial fibrillary acidic protein. Our results demonstrated that the transplantation of bone marrow mesenchymal stem cells and collagen-chitosan scaffolds to traumatic brain injury rats remarkably reduced modified neurological severity scores, shortened the average latency of the Morris water maze, increased the number of platform crossings, diminished the degeneration of damaged brain tissue, and increased the positive reaction of vascular endothelial growth factor in the transplantation and surrounding areas. At 14 days after transplantation, increased BrdU/glial fibrillary acidic protein expression and decreased BrdU/neuron specific enolase expression were observed in bone marrow mesenchymal stem cells in the injured area. The therapeutic effect of bone marrow mesenchymal stem cells and collagen-chitosan scaffolds was superior to stereotactic injection of bone marrow mesenchymal stem cells alone. To test the biocompatibility and immunogenicity of bone marrow mesenchymal stem cells and collagen-chitosan scaffolds, immunosuppressive cyclosporine was intravenously injected 12 hours before transplantation and 1–5 days after transplantation. The above indicators were similar to those of rats treated with bone marrow mesenchymal stem cells and collagen-chitosan scaffolds only. These findings indicate that transplantation of bone marrow mesenchymal stem cells in a collagen-chitosan scaffold can promote the recovery of neuropathological injury in rats with traumatic brain injury. This approach has the potential to be developed as a treatment for traumatic brain injury in humans. All experimental procedures were approved by the Institutional Animal Investigation Committee of Capital Medical University, China (approval No. AEEI-2015-035) in December 2015.

Data-driven approaches to urban flooding management require a comprehensive understanding of how heterogenous data are leveraged in tackling this problem. In this paper, we conduct an integrative review of related studies, and this is structured based on two angles: tasks and data. From the selected 69 articles on this topic, diverse tasks in tackling urban flooding are identified and categorized into eight categories, and heterogeneous data are summarized by their content type and source into eight categories. The links between tasks and data are identified by synthesizing what data are used to support the tasks in the studies. The task–data links are a many-to-many relationship in the sense that one particular data category supports multiple tasks, and one particular task uses data from multiple categories. The future research opportunities are also discussed based on our observations. This paper serves a signpost for researchers who wish to gain an overview of the heterogenous data and their use in this field and lays a foundation for studies that aim to develop a data-driven approach to tackle urban flooding.

PurposeA substantial proportion of patients with major depressive disorder (MDD) does not respond or cannot tolerate to currently available treatments. This study was to assess the safety and tolerability of Remote Limb Ischemic Preconditioning (RLIPC) as an adjunctive therapy in patients with MDD.Patients and MethodsEnrolled patients underwent RLIPC, five cycles of simultaneous bilateral arm ischemia, 5 min and followed by reperfusion of each cycle, and once daily for eight consecutive weeks. Depression and anxiety severity, and quality of life were assessed every 2 weeks. Descriptive analysis was used for safety and tolerability data.ResultsThirty-seven participants completed at least one RLIPC. Twenty-four of them (64.9%) completed the study. Twelve patients prematurely discontinued the study due to poor adherence, and one due to a mild side effect. The changes in HRSD-17, GAD-7 and QOL-6 total scores from baseline to the endpoint were significant from the end of second week treatment onwards. The responder and remission rates were 59.46% (22/37) and 54.05% (20/37) at the endpoint, respectively.ConclusionRLIPC was safe and well tolerated, and may be effective in reducing depressive symptoms in patients with MDD. Large studies are warranted to test its efficacy and safety as monotherapy or adjunctive therapy in the treatment of MDD.

Buprenorphine is a μ-opioid receptor (MOR) partial agonist used to manage pain and addiction. QTC prolongation that crosses the 10 msec threshold of regulatory concern was observed at a supratherapeutic dose in two thorough QT studies for the transdermal buprenorphine product BUTRANS®. Because QTC prolongation can be associated with Torsades de Pointes (TdP), a rare but potentially fatal ventricular arrhythmia, these results have led to further investigation of the electrophysiological effects of buprenorphine. Drug-induced QTC prolongation and TdP are most commonly caused by acute inhibition of hERG current (IhERG) that contribute to the repolarizing phase of the ventricular action potentials (APs). Concomitant inhibition of inward late Na+ (INaL) and/or L-type Ca2+ (ICaL) current can offer some protection against proarrhythmia. Therefore, we characterized the effects of buprenorphine and its major metabolite norbuprenorphine on cardiac hERG, Ca2+, and Na+ ion channels, as well as cardiac APs. For comparison, methadone, a MOR agonist associated with QTC prolongation and high TdP risk, and naltrexone and naloxone, two opioid receptor antagonists, were also studied. Whole cell recordings were performed at 37°C on cells stably expressing hERG, CaV1.2, and NaV1.5 proteins. Microelectrode array (MEA) recordings were made on human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). The results showed that buprenorphine, norbuprenorphine, naltrexone, and naloxone had no effect on IhERG, ICaL, INaL, and peak Na+ current (INaP) at clinically relevant concentrations. In contrast, methadone inhibited IhERG, ICaL, and INaL. Experiments on iPSC-CMs showed a lack of effect for buprenorphine, norbuprenorphine, naltrexone, and naloxone, and delayed repolarization for methadone at clinically relevant concentrations. The mechanism of QTC prolongation is opioid moiety-specific. This remains undefined for buprenorphine, while for methadone it involves direct hERG channel block. There is no evidence that buprenorphine use is associated with TdP. Whether this lack of TdP risk can be generalized to other drugs with QTC prolongation not mediated by acute hERG channel block warrants further study.

Indigenous animals show unique gut microbiota (GM) in the Tibetan plateau. However, it is unknown whether the hypertensive indigenous people in plateau also have the distinct gut bacteria, different from those living in plains. We sequenced the V3-V4 region of the gut bacteria 16S ribosomal RNA (rRNA) gene of feces samples among hypertensive patients (HPs) and healthy individuals (HIs) from 3 distinct altitudes: Tibetans from high altitude (3600–4500 m, n = 38 and 34), Hans from middle altitude (2260 m, n = 49 and 35), and Hans from low altitude (13 m, n = 34 and 35) and then analyzed the GM composition among hypertensive and healthy subgroups using the bioinformatics analysis, respectively. The GM of high-altitude Tibetan and middle-altitude Han HPs presented greater α- and β-diversities, lower ratio of Firmicutes/Bacteroidetes (F/B), and higher abundance of beneficial Verrucomicrobia and Akkermansia than the low-altitudes HPs did. The GM of high-altitude Tibetan and middle-altitude HIs showed greater α-diversity and lower ratio of F/B than the low-altitudes HIs did. But, β-diversity and abundance of Verrucomicrobia and Akkermansia among different subgroups of HIs did not show any differences. Conclusively, the high-altitude Tibetan and middle-altitude Han HPs have a distinct feature of GM, which may be important in their adaptation to hypertension in the plateau environments.

Exosomes can pass through the blood-brain barrier and are present in the cerebrospinal fluid (CSF). The components in exosomes, such as DNA, RNA, protein, and lipids, change greatly and are closely related to disease progression. Circular RNA (circRNA) is stable in structure and has a long half-life in exosomes without degradation. Therefore, circRNA is considered an ideal biomarker and can be used to monitor a variety of central nervous system diseases. This study aimed to investigate the expression profiles of exosomal circRNA (exo-circRNA) in CSF from patients with immune-mediated demyelinating diseases to identify suitable biomarkers for the early diagnosis of immune-mediated demyelinating diseases. circRNA expression levels in exosomes obtained from five CSF samples from immune-mediated demyelinating disease patients and five paired CSF control samples were analyzed using a hybridization array. Hierarchical clustering analysis showed that 5,095 exo-circRNAs were differentially expressed between patients with immune-mediated demyelinating diseases and paired control samples. Of these exo-circRNAs, 26 were identified as significantly differentially expressed in CSF exosomes from patients with immune-mediated demyelinating diseases (FC ≥1.5 and p ≤ 0.05). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that the upregulation or activation of protein tyrosine phosphatase receptor type F (PTPRF) and RAD23 homolog B, nucleotide excision repair protein (RAD23B) may be associated with the occurrence and development of immune-mediated demyelinating diseases. Then, a competing endogenous RNA network was constructed and centered on the most upregulated/downregulated exo-circRNAs to predict their function in immune-mediated demyelinating diseases. In addition, reverse transcription quantitative polymerase chain reaction results stating that hsa_circ_0087862 and hsa_circ_0012077 were validated in an independent cohort of subjects. Canonical correlation analysis results indicated a potential connection between exosomal hsa_circ_0012077 expression level and immunoglobulin G levels in CSF. Finally, the receiver operating characteristic (ROC) curve showed that when hsa_circ_0087862 or hsa_circ_0012077 was employed alone for diagnosing immune-mediated demyelinating diseases, the diagnostic accuracy was 100%. In conclusion, based on this study, exosomal hsa_circ_0087862 and hsa_circ_0012077 in CSF could be used as suitable biomarkers for the diagnosis of immune-mediated demyelinating disease based on their expression levels. Moreover, the upregulation or activation of PTPRF and RAD23B was potentially associated with the occurrence and development of immune-mediated demyelinating diseases.

Objective Gastrointestinal cancer is the leading cause of cancer-related death worldwide. The aim of this study was to verify whether the genotype of six short tandem repeat (STR) loci including AR, Bat-25, D5S346, ER1, ER2, and FGA is associated with the risk of gastric cancer (GC) and colorectal cancer (CRC) and to develop a model that allows early diagnosis and prediction of inherited genomic susceptibility to GC and CRC. Methods Alleles of six STR loci were determined using the peripheral blood of six colon cancer patients, five rectal cancer patients, eight GC patients, and 30 healthy controls. Fisher linear discriminant analysis (FDA) was used to establish the discriminant formula to distinguish GC and CRC patients from healthy controls. Leave-one-out cross validation and receiver operating characteristic (ROC) curves were used to validate the accuracy of the formula. The relationship between the STR status and immunohistochemical (IHC) and tumor markers was analyzed using multiple correspondence analysis. Results D5S346 was confirmed as a GC- and CRC-related STR locus. For the first time, we established a discriminant formula on the basis of the six STR loci, which was used to estimate the risk coefficient of suffering from GC and CRC. The model was statistically significant (Wilks’ lambda = 0.471, χ2 = 30.488, df = 13, and p = 0.004). The results of leave-one-out cross validation showed that the sensitivity of the formula was 73.7% and the specificity was 76.7%. The area under the ROC curve (AUC) was 0.926, with a sensitivity of 73.7% and a specificity of 93.3%. The STR status was shown to have a certain relationship with the expression of some IHC markers and the level of some tumor markers. Conclusions The results of this study complement clinical diagnostic criteria and present markers for early prediction of GC and CRC. This approach will aid in improving risk awareness of susceptible individuals and contribute to reducing the incidence of GC and CRC by prevention and early detection.

Trimethylamine N-oxide (TMAO), as a gut-derived metabolite, has been found to be associated with enhanced risk for atherosclerosis and cardiovascular disease. We presented a method for targeted profiling of TMAO and betaine in serum and food samples based on a combination of one-step sample pretreatment and proton nuclear magnetic resonance spectroscopy. The key step included a processing of sample preparation using a selective solid-phase extraction column for retention of basic metabolites. Proton signals at δ 3.29 and δ 3.28 were employed to quantify TMAO and betaine, respectively. The developed method was examined with acceptable linear relationship, precision, stability, repeatability, and accuracy. It was successfully applied to detect serum levels of TMAO and betaine in TMAO-fed mice and high-fructose-fed rats and also used to determine the contents of TMAO and betaine in several kinds of food, such as fish, pork, milk, and egg yolk.

Epoxy resin is one of the most common polymers used as part of the insulation system in key electrical assets such as power transformers and hydrogenerators. Thus, it is necessary to know their main characteristics and to evaluate their condition when subjected to High Voltage (HV). A brief review of epoxy resins’ applications as insulating materials is made, their main characteristics as insulating media are given, the improvements with nano-fillers are summarized and the main electric properties required for Partial Discharges (PD) modelling are listed. In addition, the theoretical background and state-of-the-art of the three-capacitance and analytical models for simulating PD in solid dielectrics, such as epoxy resins, are reviewed in detail. Besides, their main advantages and disadvantages are presented, some critical arguments to the modelling procedure and assumptions are made and some improvements are proposed, taking into account conclusions made from other authors using models related to the PD development process. Finally, a case study was simulated using a modified three-capacitance model and the analytical model. The PD rate, q-φ-n diagrams and the minimum, mean and maximum PD electric charge are compared with measurements reported in the literature. Simulation results are in reasonable agreement with measured values. Capacitance models can be implemented in general purpose electric circuit simulation packages; however, its simulation is computationally expensive. Additional to this, although the modified three-capacitance model is not as accurate as finite elements or analytical models, results are also in agreement with real data.

A three-dimensional computational model of two CRH2 trains passing by each other in a tunnel was developed using finite volume method with moving mesh, to investigate the characteristics of air wave and flow field around high-speed trains. Two meeting scenarios (i.e. meeting at the same train speeds and at different train speeds) and five train speeds (i.e. 200, 250, 300, 350, and 400 km/h) were examined. The computational model is demonstrated to be qualified to investigate the characteristics of air wave for two trains meeting in a tunnel. The pressure distribution and velocity vectors of two trains meeting in a tunnel were revealed, and the typical features of the corresponding air wave curve were discussed. Furthermore, the variation regularity of pressure amplitudes and the relationship between pressure wave amplitude and train speed were also analyzed. The results indicate that two trains with a large speed difference should be avoided when they pass by each other in a tunnel. These findings are helpful to guide the design of trains and tunnel structures and the dispatching management of rail transit.

BACKGROUND:Osteosarcoma (OS) is a primary malignant bone tumor with a high fatality rate. Many circRNAs have been proved to play important roles in the pathogenesis of some diseases. However, the occurrence of circRNAs in OS remains little known. METHODS:The circular RNA (circRNA) expression file GSE96964 dataset, which included seven osteosarcoma cell lines and one control sample (osteoblast cell line), was downloaded from the Gene Expression Omnibus (GEO) database to explore the potential function of circRNAs in osteosarcoma by competing endogenous RNA (ceRNA) analysis. Three gene expression profiles of OS were downloaded from GEO database and then used for the pathway enrichment analysis, Venn analysis and protein-protein interaction (PPI) network analysis. Real-time qPCR validation and RNA interference were conducted to verify our prediction. RESULTS:Differentially expressed circRNAs between OS and control, including 8 up-regulated and 102 down-regulated circRNAs, were generated and ceRNA analysis for 5 most up-regulated or 5 most down-regulated circRNAs in OS were then performed. The pathway enrichment analysis of gene expression profiles indicated differentially expressed genes (DEGs) of three gene profiles significantly enriched in cell cycle pathway, cell adhesion molecules (CAMs) pathway, oxidative phosphorylation pathway, cytokine-cytokine receptor interaction pathway, p53 signaling pathway and proteoglycans in cancer pathway, which were critical important pathways in the pathogenesis of OS. The Venn analysis showed that 2 (one is a pseudogene) up-regulated and 39 down-regulated DEGs were co-expressed in all three gene profiles. Then PPI networks of 41 co-expressed DEGs (up- and down-regulated DEGs) were constructed to predict their functions using the GeneMANIA. The expression levels of these related RNAs also matched our predictions really well. CONCLUSION:Ultimately, we found cell adhesion molecule 1 (CADM1) gene was not only a co-expression mRNA of the three mRNA expression profiles of OS, but also are predicted to be regulated by hsa_circ_0032462, hsa_circ_0028173, hsa_circ_0005909 by functioning as miRNAs 'Sponge' in human osteosarcoma. These over-expressed circRNAs may result in the over expression of CADM1 which promote the development of OS. We envision this discovery of these important moleculars, incuding hsa_circ_0032462, hsa_circ_0028173, hsa_circ_0005909 and CADM1 may lead to further development of new concepts, thus allowing for more opportunities in diagnosis and therapy of OS.

The oil-based nanofluids with greater dielectric strength have attracted much attention as a crucial insulating materials in high-voltage oil-immersed power equipment. In fact, the different microstructures of the transformer oil-based nanofluids (TNFs) would result in different dielectric properties. In this work, the broadband dielectric spectroscopy measurement was used to establish the linkage between the electric double layer (EDL) and dielectric response properties of TNFs which was performed at 298K temperature and with frequency range from 10-2Hz∼106Hz. The modified Havriliak-Negami (HN) model function was used to analyze the measured results. The results demonstrate that both the real and imaginary parts of dielectric spectra of two kinds of oil are composed of the conductivity and polarization process. Compared with pure oil, two polarization process could be observed for the TNFs, explained by the EDL structure reasonably. The introduction of the EDL structure provides an idea to account for the insulating strength improvement of TNFs for the first time.

Objective: To investigate whether number of doses per day and number of medications are significantly associated with the number of readmissions and to study the association of readmission frequency with other medical and socio-demographic variables. Methods: Retrospective cross-sectional study involving 432 patients who were readmitted within 15 days of previous hospital discharge between January 1, 2013 and March 31, 2013. Relevant medical records were collected from the national electronic databases of every public tertiary hospital in Singapore. Significant variables (p

Background The aim of this study was to determine the expression stabilities of 12 common internal reference genes for the relative quantitation analysis of target gene expression performed by reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) in human laryngeal cancer. Methods Hep-2 cells and 14 laryngeal cancer tissue samples were investigated. The expression characteristics of 12 internal reference gene candidates (18S rRNA, GAPDH, ACTB, HPRT1, RPL29, HMBS, PPIA, ALAS1, TBP, PUM1, GUSB, and B2M) were assessed by RT-qPCR. The data were analyzed by three commonly used software programs: geNorm, NormFinder, and BestKeeper. Results The use of the combination of four internal reference genes was more appropriate than the use of a single internal reference gene. The optimal combination was PPIA + GUSB + RPL29 + HPRT1 for both the cell line and tissues; while the most appropriate combination was GUSB + RPL29 + HPRT1 + HMBS for the tissues. Conclusions Our recommended internal reference genes may improve the accuracy of relative quantitation analysis of target gene expression performed by the RT-qPCR method in further gene expression research on laryngeal tumors.

To evaluate the degradation behavior of theophylline/chitosan/β-cyclo-dextrin microspheres, we performed both in vitro study by putting the microspheres in phosphate buffered saline or in phosphate buffer saline with enzyme and in vivo study by implanting the microspheres into the back of male Sprague-Dawley rats. The results showed that microspheres were degraded in enzymatic hydrolysis and phosphate buffer saline, which were degraded faster in 0.2 mg/mL lysozyme than in phosphate buffer saline. The morphology of microspheres in phosphate buffer saline and enzyme solution developed rough surfaces, and showed irregular shape and pores after 8 weeks. The microspheres were degraded in vivo within 8 weeks with irregular, sheet, porous morphology, and the diameters were smaller than 5 μm. These results indicated that the theophylline/chitosan/β-cyclodextrin microspheres had a good degradation both in vitro and in vivo which can be used as a pulmonary drug delivery carrier.

Metal-enclosed switchgear, which are widely used in the distribution of electrical energy, play an important role in power distribution networks. Their safe operation is directly related to the reliability of power system as well as the power quality on the consumer side. Partial discharge detection is an effective way to identify potential faults and can be utilized for insulation diagnosis of metal-enclosed switchgear. The transient earth voltage method, an effective non-intrusive method, has substantial engineering application value for estimating the insulation condition of switchgear. However, the practical application effectiveness of TEV detection is not satisfactory because of the lack of a TEV detection application method, i.e., a method with sufficient technical cognition and analysis. This paper proposes an innovative online PD detection system and a corresponding application strategy based on an intelligent feedback distributed TEV wireless sensor network, consisting of sensing, communication, and diagnosis layers. In the proposed system, the TEV signal or status data are wirelessly transmitted to the terminal following low-energy signal preprocessing and acquisition by TEV sensors. Then, a central server analyzes the correlation of the uploaded data and gives a fault warning level according to the quantity, trend, parallel analysis, and phase resolved partial discharge pattern recognition. In this way, a TEV detection system and strategy with distributed acquisition, unitized fault warning, and centralized diagnosis is realized. The proposed system has positive significance for reducing the fault rate of medium voltage switchgear and improving its operation and maintenance level.

In this paper, a comparison of positive streamer diffusion propagation is carried out in three configurations of oil transformers: mineral transformer oil, mineral oil with solid dielectric barriers, and a nanofluid. The results have been solved using a finite-element method with a two-dimensional (2D) axi-symmetric space dimension selected. Additionally, previous results from other research has been reviewed to compare the results obtained. As expected, it is confirmed that the nanoparticles improve the dielectric properties of the mineral oil. In addition, it is observed that the dielectric solid blocks the propagation of the streamer when it is submerged with a horizontal orientation, thus perpendicular to the applied electric field. The computer used, with four cores (each 3.4 GHz) and 16 GB of RAM, was not sufficient for performing the simulations of the models with great precision. However, with these first models, the tendency of the dielectric behavior of the oil was obtained for the three cases in which the streamer was acting through the transformer oil. The simulation of these models, in the future, in a supercomputer with a high performance in terms of RAM memory may allow us to predict, as an example, the best concentration of nanoparticles to retard the streamer inception. Finally, other dielectric issues will be predicted using these models, such as to analyze the advantages and drawbacks of the presence of dielectrics inside the oil transformer.

Corona discharge could be a serious hazard to the outdoor insulation of a high-voltage (HV) system and also is an important detection issue for insulation status diagnosis. In this study, a double-helix-ultrasonic-array (DHUA) sensor was developed for corona positioning, which showed a good sensitivity to the ultrasonic signal originating from corona discharge and a satisfied directional response in static beam patterns. Based on the matting-based image fusion method, the acoustic intensity matrix was fused to a visual scene in real-time. This ultrasonic visualization technology was then evaluated with a simulation test and performed in a real air insulated substation (AIS), and showed a satisfied performance in terms of sensitivity and spatial location resolution.

Optical detection is reliable in intrinsically characterizing partial discharges (PDs). Because of the great volume and high-level power supply of the optical devices that can satisfy the requirements in photosensitivity, optical PD detection can merely be used in laboratory studies. To promote the practical application of the optical approach in an actual power apparatus, a silicon photomultiplier (SiPM)-based PD sensor is introduced in this paper, and its basic properties, which include the sensitivity, pulse resolution, correlation with PD severity, and electromagnetic (EM) interference immunity, are experimentally evaluated. The stochastic phase-resolved PD pattern (PRPD) for three typical insulation defects are obtained by SiPM PD detector and are compared with those obtained using a high-frequency current transformer (HFCT) and a vacuum photomultiplier tube (PMT). Because of its good performances in the above aspects and its additional advantages, such as the small size, low power supply, and low cost, SiPM offers great potential in practical optical PD monitoring.

Sulfur hexafluoride (SF6) gas-insulated electrical equipment is widely used in high-voltage (HV) and extra-high-voltage (EHV) power systems. Partial discharge (PD) and local heating can occur in the electrical equipment because of insulation faults, which results in SF6 decomposition and ultimately generates several types of decomposition products. These SF6 decomposition products can be qualitatively and quantitatively detected with relevant detection methods, and such detection contributes to diagnosing the internal faults and evaluating the security risks of the equipment. At present, multiple detection methods exist for analyzing the SF6 decomposition products, and electrochemical sensing (ES) and infrared (IR) spectroscopy are well suited for application in online detection. In this study, the combination of ES with IR spectroscopy is used to detect SF6 gas decomposition. First, the characteristics of these two detection methods are studied, and the data analysis matrix is established. Then, a qualitative and quantitative analysis ES-IR model is established by adopting a two-step approach. A SF6 decomposition detector is designed and manufactured by combining an electrochemical sensor and IR spectroscopy technology. The detector is used to detect SF6 gas decomposition and is verified to reliably and accurately detect the gas components and concentrations.