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Clearly delineating the tumor foci based on multimodal imaging techniques and precisely guiding the minimally invasive therapy are pivotal to completely remove tumors, especially for early micro-tumor lesions. Nevertheless, single-mode imaging techniques are difficult to accurately visualize the tumor region, and the mono-therapeutic strategy is hardly a complete removal of the tumor. In this study, we prepare a biodegradable amphiphilic polymer containing poly­(aspartic acid). It is further self-assembled with Bi3+ and ultrasmall Fe3O4 to form a multifunctional nanocomplex (Bi/Fe3O4@P3), which served as a CT/MRI dual-imaging contrast agent and enhanced the photothermal/chemodynamic synergistic therapy. In addition, to enhance the photothermal efficiency, the thermal stress also elevated the level of intracellular H2O2, which would facilitate the Fenton reaction between Bi3+/Fe2+ and H2O2 and improve the chemodynamic therapy (CDT) efficacy. Particularly, Bi/Fe3O4@P3 would concurrently deplete the abundant intracellular GSH through the coordination of Bi3+ with GSH to further potentiate the PTT/CDT synergistic tumoricidal efficacy. Therefore, our study was expected to provide a promising theranostic nano-agent and potential comprehensive therapeutic strategy for microtumors.

Abstract Hepatocellular carcinoma (HCC) is a malignancy with poor prognosis. Abnormal expression of H3–H4 histone chaperones has been identified in many cancers and holds promise as a biomarker for diagnosis and prognosis. However, systemic analysis of H3–H4 histone chaperones in HCC is still lacking. Here, we investigated the expression of 19 known H3–H4 histone chaperones in HCC. Integrated analysis of multiple public databases indicated that these chaperones are highly expressed in HCC tumor tissues, which was further verified by immunohistochemistry (IHC) staining in offline samples. Additionally, survival analysis suggested that HCC patients with upregulated H3–H4 histone chaperones have poor prognosis. Using LASSO and Cox regression, we constructed a two-gene model (ASF1A, HJURP) that accurately predicts prognosis in ICGC-LIRI and GEO HCC data, which was further validated in HCC tissue microarrays with follow-up information. GSEA revealed that HCCs in the high-risk group were associated with enhanced cell cycle progression and DNA replication. Intriguingly, HCCs in the high-risk group exhibited increased immune infiltration and sensitivity to immune checkpoint therapy (ICT). In summary, H3–H4 histone chaperones play a critical role in HCC progression, and the two-gene (ASF1A, HJURP) risk model is effective for predicting survival outcomes and sensitivity to immunotherapy for HCC patients.

A powder-metallurgy MoNbTaTiV refractory high-entropy alloy synthesized by mechanical alloying (MA) and spark plasma sintering was subjected to hot deformations at different temperatures and strain rates. The microstructural morphologies were characterized, and component element segregation was elucidated. With grain refinement and lattice strain increase, the large inhomogeneous milled powder became refined and homogeneous after the MA. Component element segregation was observed at relatively low deformation temperatures and high strain rates. As the deformation temperature increased and the strain rate decreased, the segregation gradually disappeared, which was attributed to dislocation movement.

Medical extended reality (MXR) applications are rapidly evolving with innovative use cases in medical training and surgical planning, among others. MXR benefits from seamless connectivity, like that promised by 5G, to facilitate its functionality where users can interact with virtual content, share views, and collaborate. In this paper, we identify practical implementation approaches for MXR connectivity and characterize the traffic models of selected example MXR applications. The traffic models were obtained through a data-oriented workflow to showcase general procedures and considerations in modeling traffic patterns for diverse MXR applications. The proposed models correlate the network traffic with specific MXR deployments (e.g., remote rendering, display mirroring) and events like head rotation, hand movements, and image download. Accordingly, they can be used to formulate the traffic models for other MXR applications to support an application-specific approach to the evaluation of relevant MXR connectivity risks.

Laser interstitial thermal therapy (LITT), which ablates diseased brain tissues via hyperthermia, has offered novel treatment approach for epilepsy; however, the current LITT protocols still lack ablation selectivity and disease‐modifying efficacy. A second near‐infrared (NIR‐II) activatable nitric oxide (NO) releasing nanoactuator is reported here for photothermal combinational modulation of epileptogenic focus. The nanoactuator is prepared by conjugating NO donor S‐nitrosoglutathione (GSNO) onto polydopamine‐coated gold (Au) nanoparticles (NPs), which shows excellent photothermal conversion capability and controlled NO‐releasing property upon illumination in the NIR‐II window. Both in vitro and in vivo study demonstrate that the nanoactuator could exert stronger cell killing effects as compared to its counterpart. Furthermore, the NIR‐II‐activated NO release could inhibit P‐gp expression by regulating NF‐κb pathway, resulting in reprogramming of epileptogenic microenvironment. This study thus offers a novel regulating strategy for the treatment of drug‐resistant epilepsy.

Abstract Background Jaundice occurs in some pancreatic disease. However, its occurrences and role in pancreatic neuroendocrine neoplasms (PNENs) has not been well studied. In this study we showed the association between jaundice and the risk of high grade and poorly differentiated PNENs. Methods Ninety-three patients with head-neck PNENs were included. Poorly differentiated pancreatic neuroendocrine neoplasms were defined by a ki67 index > 55.0%. Logistic regression was used to show the association between demographic information, clinical signs and symptoms and the risk of poorly differentiated tumors. A nomogram model was developed to predict poorly differentiated tumor. Results Eight of 93 PNEN patients (8.6%) had jaundice. The age and ki67 index in patients with jaundice were significantly higher than those patients without jaundice. All jaundice occurred in patients with grade 3 PNENs. Mutivariable regression analysis showed that age (odds ratio(OR) = 1.10, 95% confidence interval (CI):1.02–1.19), tumor size (OR = 1.42, 95%CI:1.01-2.00) and jaundice (OR = 14.98, 95%CI: 1.22-184.09) were associated with the risk of poorly differentiated PNENs. The age and size combination showed a good performance in predicting poorly differentiated PNENs (area under the curve (AUC) = 0.81, 95% CI: 0.71–0.90). The addition of jaundice further improved the age- and size-based model (AUC = 0.86, 95% CI: 0.78–0.91). A nomogram was developed based on age, tumor size and jaundice. Conclusion Our data showed that jaundice was associated with the risk of high grade PNENs and poorly differentiated PNENs.

This study involved the preparation of natural rubber-based composites incorporating varying proportions of heavy metals and rare earth oxides (Sm2O3, Ta2O5, and Bi2O3). The investigation analyzed several parameters of the samples, including mass attenuation coefficients (general, photoelectric absorption, and scattering), linear attenuation coefficients (μ), half-value layers (HVLs), tenth-value layers (TVLs), mean free paths (MFPs), and radiation protection efficiencies (RPEs), utilizing the Monte Carlo simulation software Geant4 and the WinXCom database across a gamma-ray energy spectrum of 40–150 keV. The study also compared the computational discrepancies among these measurements. Compared to rubber composites doped with single-component fillers, multi-component mixed shielding materials significantly mitigate the shielding deficiencies observed with single-component materials, thereby broadening the γ-ray energy spectrum for which the composites provide effective shielding. Subsequently, the simulation outcomes were juxtaposed with experimental data derived from a 133Ba (80 keV) γ-source. The findings reveal that the simulated results align closely with the experimental observations. When compared to the WinXCom database, the Geant4 software demonstrates superior accuracy in deriving radiation shielding parameters and notably enhances experimental efficiency.

PurposeTo develop and validate a deep learning radiomics (DLR) model that uses X-ray images to predict the classification of osteoporotic vertebral fractures (OVFs).Material and methodsThe study encompassed a cohort of 942 patients, involving examinations of 1076 vertebrae through X-ray, CT, and MRI across three distinct hospitals. The OVFs were categorized as class 0, 1, or 2 based on the Assessment System of Thoracolumbar Osteoporotic Fracture. The dataset was divided randomly into four distinct subsets: a training set comprising 712 samples, an internal validation set with 178 samples, an external validation set containing 111 samples, and a prospective validation set consisting of 75 samples. The ResNet-50 architectural model was used to implement deep transfer learning (DTL), undergoing -pre-training separately on the RadImageNet and ImageNet datasets. Features from DTL and radiomics were extracted and integrated using X-ray images. The optimal fusion feature model was identified through least absolute shrinkage and selection operator logistic regression. Evaluation of the predictive capabilities for OVFs classification involved eight machine learning models, assessed through receiver operating characteristic curves employing the “One-vs-Rest” strategy. The Delong test was applied to compare the predictive performance of the superior RadImageNet model against the ImageNet model.ResultsFollowing pre-training separately on RadImageNet and ImageNet datasets, feature selection and fusion yielded 17 and 12 fusion features, respectively. Logistic regression emerged as the optimal machine learning algorithm for both DLR models. Across the training set, internal validation set, external validation set, and prospective validation set, the macro-average Area Under the Curve (AUC) based on the RadImageNet dataset surpassed those based on the ImageNet dataset, with statistically significant differences observed (P

Ischemic stroke (IS) refers to local brain tissue necrosis which is caused by impaired blood supply to the carotid artery or vertebrobasilar artery system. As the second leading cause of death in the world, IS has a high incidence and brings a heavy economic burden to all countries and regions because of its high disability rate. In order to effectively treat IS, a large number of drugs have been designed and developed. However, most drugs with good therapeutic effects confirmed in preclinical experiments have not been successfully applied to clinical treatment due to the low accumulation efficiency of drugs in IS areas after systematic administration. As an emerging strategy for the treatment of IS, stimuli-responsive nanomedicines have made great progress by precisely delivering drugs to the local site of IS. By response to the specific signals, stimuli-responsive nanomedicines change their particle size, shape, surface charge or structural integrity, which enables the enhanced drug delivery and controlled drug release within the IS tissue. This breakthrough approach not only enhances therapeutic efficiency but also mitigates the side effects commonly associated with thrombolytic and neuroprotective drugs. This review aims to comprehensively summarize the recent progress of stimuli-responsive nanomedicines for the treatment of IS. Furthermore, prospect is provided to look forward for the better development of this field.

The potential of Ferrimagnetic vortex iron oxide nanoring-mediated mild magnetic hyperthermia (FVIO-MHT) in solid tumor therapy has been demonstrated. However, the impact of FVIO-MHT on the tumor microenvironment (TME) remains unclear. This study utilized single-cell transcriptome sequencing to examine the alterations in the TME in response to FVIO-MHT in breast cancer. The results revealed the cellular composition within the tumor microenvironment (TME) was primarily modified due to a decrease in tumor cells and an increased infiltration of myeloid cells. Subsequently, an enhancement in active oxygen (ROS) metabolism was observed, indicating oxidative damage to tumor cells. Interestingly, FVIO-MHT reprogrammed the macrophages’ phenotypes, as evidenced by alterations in the transcriptome characteristics associated with both classic and alternative activated phenotypes. And an elevated level of ROS generation and oxidative phosphorylation suggested that activated phagocytosis and inflammation occurred in macrophages. Additionally, cell–cell communication analysis revealed that FVIO-MHT attenuated the suppression between tumor cells and macrophages by inhibiting phagocytic checkpoint and macrophage migration inhibitory factor signaling pathways. Inhibition of B2m, an anti-phagocytosis checkpoint, could promote macrophage-mediated phagocytosis and significantly inhibit tumor growth. These data emphasize FVIO-MHT may promote the antitumor capabilities of macrophages by alleviating the suppression between tumor cells and macrophages.

In the present work, low-current-density electropulsing was applied to study the recrystallization behavior of a hot-rolled TiBw/TA15 composite. To highlight the athermal effect of electropulsing, traditional heat treatment experiments on composite materials were conducted under the same conditions. Test results indicated that recrystallization behavior can be improved compared with that in traditional heat treatment. The potential mechanism by which electropulsing promotes recrystallization was investigated, and the influence of the reinforcement phase on recrystallization was discussed. This work will provide freedom for the composite's process design and microstructure control.

Electrically-assisted diffusion bonding (EADB) of a TiBw/TA15 composite with a novel network architecture was studied under a vacuum degree of 3 × 10−3 Pa in this work. Traditional diffusion bonding (TDB) was also investigated to verify the electroplasticity effect. Characterization of the bonding interface revealed that the interface bonding ratio and shear strength increased with bonding time, and the maximum shear strength of the EADB sample could reach 786 MPa when bonded at 4.23 A/mm2 and 2 MPa for 60 min. However, when bonded in the same condition, the EADB sample achieved higher bonding quality than the TDB sample did. Moreover, the potential mechanism through which electropulsing promoted diffusion bonding was studied in detail. The findings provide ideas for EADB of titanium matrix composites.

Abstract Background Two trials in Chinese population showed that endovascular treatment (EVT) alone was noninferior to alteplase follow by EVT at 90 days. However, results of long-term clinical outcomes remain unknown. We reported the results of prespecified 18-month analysis of the DEVT trail. Materials and methods We assessed clinical outcomes 18 months after patients were randomly assigned to receive EVT alone or bridging therapy for acute ischemic stroke (AIS). The primary outcome was the proportion of functional independence [modified Rankin scale (mRS), 0–2] at 18 months. Secondary outcomes included all-cause mortality and the quality of life at 18 months as measured by means of a health utility index according to the European Quality of Life 5-Dimension 5-level scale (EQ-5D-5L). Kaplan-Meier event curves were used to investigate the risk of mortality in participants with EVT alone or bridging therapy. Results Among 234 patients (EVT alone, n = 116; bridging therapy, n = 118) in the DEVT trial, only 231 (98.7%) patients were extended follow-up to 18 months. A total of 60 (51.7%) patients in the EVT alone achieved functional independence vs 56 (47.5%) patients in the bridging therapy (difference, 4.3%; 1-sided 97.5% CI, − 8.4% to ∞, P for noninferiority =0.014). No significant between-group difference was detected in EQ-5D-5L score (0.81 vs 0.73; difference, 0; 95% CI, 0 to 0.005). The cumulative mortality was 27.6% in the EVT alone and 28.8% in the bridging therapy. Conclusion At 18 months follow-up, EVT alone was noninferior to bridging therapy regarding favorable functional outcome in patients with AIS. Trial registration Trial was registered on Chinese Clinical Trial Registry (ChiCTR-IOR-17013568) on 27/11/2017.

To precisely identify high voltage transmission line fittings and guide a line patrol robot in executing obstacle-crossing maneuvers tailored to diverse fittings, a real-time detection network based on deep learning DeblurGANv2 and YOLOv5 target detection algorithm was proposed. Addressing challenges inherent in the YOLOv5 algorithm, characterized by a substantial network model, high computational overhead, and diminished operational efficiency, a judicious lightweight refinement is undertaken to enhance the algorithm’s detection speed. The original network was improved by replacing CSPDarknet-53 with Shufflenetv2 and integrating an ECA module into Shufflenetv2, thereby enhancing the model’s focus on relevant features. Simultaneously, the DeblurGANv2 super-resolution reconstruction algorithm is employed to rectify the blurriness of the fittings’ images, resulting in the production of high-quality images and enhancing the accuracy of recognition. Experimental results obtained from self-created datasets demonstrate that the proposed method exhibits a reduction of 50.2% in parameter quantity and a decrease of 62.7% in weight file size when compared to the original YOLOv5 model. Additionally, the proposed method achieves a 1.3% increase in mAP@(0.5). The proposed method demonstrates successful detection of high voltage transmission line fittings, thereby ensuring the accuracy of fuzzy target detection.

The fifth-generation (5G) cellular communication technology introduces technical advances that can expand medical device access to connectivity services. However, assessing the safety and effectiveness of emerging 5G-enabled medical devices is challenging as relevant evaluation methods have not yet been established. In this paper, we propose a design model for 5G testbed as a regulatory science tool (TRUST) for assessing 5G connectivity enablers of medical device functions. Specifically, we first identify application specific testing needs and general testing protocols. Next, we outline the selection and customization of key system components to create a 5G testbed. A TRUST demonstration is documented through a realistic 5G testbed implementation along with the deployment of a custom-built example use-case for 5G-enabled medical extended reality (MXR). Detailed configurations, example collected data, and implementation challenges are presented. The openness of the TRUST design model allows a TRUST testbed to be easily extended and customized to incorporate available resources and address the evaluation needs of different stakeholders.

Here the authors find that the mRNA of GYS2, the liver-specific glycogen synthase, is a substrate of METTL3 and IGF2BP2 and that m6A-mediated regulation of Gys2 mRNA is critical for the maintenance of liver glycogenesis in mammals during growth, such as mice and rats.

Nucleation is a basic issue in film science and technology, and it plays a vital role in the field of functional devices characterized in ultra-thin and continuous thin films. In this paper, Au clusters were deposited on three different substrates (BOPP, Si (100) and carton support film) by means of magnetron sputtering with or without air plasma pretreatment. The results show that plasma treatment conducted on BOPP substrate decreased the water contact angle significantly, indicating an enhanced surface energy of BOPP substrate. The introduction of polar groups (C–O/C–N, C=O/N–C=O and O–C=O) as well as a modified topology were responsible for the improvement of hydrophilicity. Au nanoparticles prepared on untreated substrates exhibited a non-uniform topology independent of substrate type. After plasma treatment, Au nucleation densities were increased greatly, and the nucleus sizes were much smaller. Based on the thermodynamics theory of heterogeneous nucleation, by means of plasma treatment, the substrate surface energy was enhanced and the film-substrate interfacial energy was decreased simultaneously, and both of them contributed to the higher nucleation density and smaller cluster size.

Abstract Background The role of serum high-density lipoprotein cholesterol (HDL-c) in tumorigenesis are observed in several endocrine-related cancers. However, its role in pancreatic neuroendocrine neoplasms (PNENs) has not been understood. In the current study, the relationship between HDL-c levels and malignant behavior in PNENs was explored. Methods One hundred ninety-seven patients with histopathology confirmed PNENs were included. PNENs were divided into three grades (G1, G2 and G3) as 2017 WHO classification based on ki67 index and mitosis count. The demographic data, clinical information, tumor morphological and pathological features (organs invasion, lymph node metastasis, vascular invasion and perineural invasion), and serum tumor biomarkers were collected. The relationships between HDL-c levels and malignant behaviors in PNENs were analyzed using logistic regression analysis. Models were also developed for the identification of high grade PNENs. Results The levels of serum HDL-c in G2/G3 tumor were significantly lower than that in G1 tumor (P = 0.031). However, no such difference was found between G3 and G1/G2. The proportions of low HDL-c (≤ 0.9 mmol/L) were higher in high-grade PNENs (G2/G3 or G3) than those in low-grade (G1 or G1/G2) (29.0 vs 15.2%, P = 0.032; 37.0 vs 20.5%, P = 0.023). The risk of G2/G3 tumors in patients with high serum HDL-c levels was decreased (odds ratio (OR) = 0.35, 95% confidence interval (CI): 0.12–0.99). Similarly, the risk of G3 PNENs increased in patients with low HDL-c levels (OR = 2.51, 95%CI:1.12–5.60). HDL-c level was also associated with a high ki67 index (> 55%) (OR = 0.10, 95%CI: 0.02–0.51) and neuroendocrine carcinoma G3 (OR = 0.21, 95%CI: 0.06–0.80). The area under the curve (AUC) of HDL-c + tumor size + age was 0.85 (95% CI: 0.79–0.91) in identifying G2/G3 PNENs, and HDL-c (> 0.9 mmol/L) + tumor size + age had an AUC of 0.77 (95% CI: 0.70–0.84) in identifying G3 PNENs. HDL-c level was associated with lymph node metastasis (OR = 0.24, 95%CI:0.08–0.99). Conclusion Serum HDL-c levels were significantly associated with malignant behaviors in PNENs, in particular to tumor grade and lymph node metastasis.

This study investigates the mechanical properties of exceptionally high-strength steel produced by wire and arc additive manufacturing (WAAM), using the 304 stainless steel wire and the low carbon wire (LCS). The study found that annealing treatment can enhance the steel’s mechanical properties. The microstructure in the LCS layer changed from ferrite to bainite and then to a mixture of austenite, pearlite, and bainite with increasing annealing temperature. In contrast, the SS layer retained its martensitic structure, albeit with altered lath sizes. The annealing treatment also improved the orientation of the grains in the steel. The optimal annealing temperature observed for the steel was 900 ℃, which resulted in a maximum tensile strength of 1176 MPa along the Y direction and 1255 MPa along the Z direction. Despite the superior mechanical properties, the LCS layer still exhibited failure during tensile testing due to its lower hardness. The study suggests that annealing treatment can be a useful technique for enhancing the mechanical properties of high-strength steel in WAAM applications.

Secondary spinal cord injury (SSCI) is the second stage of spinal cord injury (SCI) and involves vasculature derangement, immune response, inflammatory response, and glial scar formation. Bioactive additives, such as drugs and cells, have been widely used to inhibit the progression of secondary spinal cord injury. However, the delivery and long-term retention of these additives remain a problem to be solved. In recent years, hydrogels have attracted much attention as a popular delivery system for loading cells and drugs for secondary spinal cord injury therapy. After implantation into the site of spinal cord injury, hydrogels can deliver bioactive additives in situ and induce the unidirectional growth of nerve cells as scaffolds. In addition, physical and chemical methods can endow hydrogels with new functions. In this review, we summarize the current state of various hydrogel delivery systems for secondary spinal cord injury treatment. Moreover, functional modifications of these hydrogels for better therapeutic effects are also discussed to provide a comprehensive insight into the application of hydrogels in the treatment of secondary spinal cord injury.

Hollyhock (Alcea rosea (Linn). Cavan) is an herbaceous flowering plant with significant applications in urban greening, soil remediation, and traditional medicine. However, its genetic diversity and molecular characteristics at the population level have not been explored yet. Here, the phenotypic and genetic diversity of 162 hollyhock accessions from China revealed extensive variation among 11 traits and strong correlations between several quantitative traits. Whole-genome re-sequencing of 32 randomly chosen accessions identified 10,468,760 core single-nucleotide polymorphisms (SNPs) distributed evenly across the genome, except for on chromosome 21, and the average nucleotide diversity (π) was calculated to be 0.00397. Principal component analysis showed that these 32 accessions could be divided into four subpopulations, which was in agreement with the population structure analysis, and the subpopulations were strongly correlated with geographic location. A neighbor-joining dendrogram displayed similar clusters, except for accessions HuB25 and HLJ28, which formed two separate clusters. Our findings illuminate the genetic diversity in hollyhock and provide valuable information for hollyhock breeding.

Iridoid glycoside is the important secondary metabolite and the main active component in Rehmannia glutinosa. However, the mechanisms that underlie the regulation of iridoid glycoside biosynthesis remain poorly understood in R. glutinosa. Herein, the analysis of RNA-seq data revealed that 3,394 unigenes related to the biosynthesis of secondary metabolites were identified in R. glutinosa. A total of 357 unigenes were involved in iridoid glycoside synthesis, in which the highly conservative genes, such as DXS, DXR, GPPS, G10H, and 10HGO, in organisms were overexpressed. The analysis of the above genes confirmed that the co-occurrence ratio of DXS, DXR, and GPPS was high in plants. Further, our results showed that under normal and 5-azacytidine (5-azaC) treatment, the expression levels of DXS, DXR, GPPS, G10H, and 10HGO were consistent with the iridoid glycoside accumulation in R. glutinosa, in which the application of the different concentrations of 5-azaC, especially 50 μM 5-azaC, could significantly upregulate the expression of five genes above and iridoid glycoside content. In addition, the changes in the spatiotemporal specificity of degree and levels of DNA methylation were observed in R. glutinosa, in which the hemi-methylation was the main reason for the change in DNA methylation levels. Similar to the changes in 5-methyl cytosine (5mC) content, the DNA demethylation could be induced by 5-azaC and responded in a dose-dependent manner to 15, 50, and 100 μM 5-azaC. Taken together, the expression of iridoid glycoside synthesis gene was upregulated by the demethylation in R. glutinosa, followed by triggering the iridoid glycoside accumulation. These findings not only identify the key genes of iridoid glycoside synthesis from R. glutinosa, but also expand our current knowledge of the function of methylation in iridoid glycoside accumulation.

ObjectivesTo investigate the association between the perivascular adipose tissue (PVAT) fat attenuation index (FAI) derived from coronary computed tomography angiography (CCTA) and the prevalence of in-stent restenosis (ISR) in patients with coronary stent implantation.MethodsA total of 117 patients with previous coronary stenting referred for invasive coronary angiography (ICA) were enrolled in this retrospective observational analysis. All patients underwent CCTA between July 2016 and November 2021. The deep learning-based (DL-based) method was used to analyze and measure the peri-stent FAI value. Additionally, the relationship between hematological and biochemical parameters collected from all the patients was also explored. The least absolute shrinkage and selection operator (LASSO) method was applied to the most useful feature selection, and binary logistic regression was used to test the association between the selected features and ISR. The predictive performance for ISR of the identified subgroups was evaluated by calculating the area under the curve (AUC) of receiver operator curves plotted for each model. The Pearson correlation coefficient was used to assess the correlation of peri-stent FAI values with degrees of ISR.ResultsThe peri-stent FAI values in the ISR group were significantly higher than those in the non-ISR group (−78.1 ± 6.2 HU vs. −87.2 ± 7.3 HU, p < 0.001). The predictive ISR features based on the LASSO analysis were peri-stent FAI, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (ApoA1), and high-sensitivity c-reactive protein (hs-CRP), with an AUC of 0.849, 0.632, 0.620, and 0.569, respectively. Binary logistic regression analysis determined that peri-stent FAI was uniquely and independently associated with ISR after adjusting for other risk factors (odds ratio [OR] 1.403; 95% CI: 1.211 to 1.625; p < 0.001). In the subgroup analysis, the AUCs of the left anterior descending coronary artery (LAD), left circumflex coronary artery (LCx), and right coronary artery (RCA) stents groups were 0.80, 0.87, and 0.96, respectively. The Pearson's correlation coefficient indicated a term moderately correlation between ISR severity and peri-stent FAI values (r = 0.579, P < 0.001).ConclusionsThe peri-stent FAI can be used as an independently non-invasive biomarker to predict ISR risk and severity after stent implantation.

Intelligent vehicles and Advanced Driver Assistance Systems (ADAS) are being developed rapidly over the past few years. Many applications such as vehicle localization, environment perception, and path planning have shown promising potentialities. While there is great interest in migrating from complete human-controlled vehicles towards fully autonomous vehicles, it is natural that researchers spending more effort trying to understand the interaction between vehicles with various levels of automation in large-scale traffic scenarios. Next-generation vehicles are expected to have the capacity of evaluating driver conditions, vehicle capabilities, surrounding traffic contexts, and take advantage of such knowledge to ensure safe and efficient driving. Three general research questions are raised to achieve this goal, which are (i) how can we acquire sufficient data, (ii) how to evaluate and understand driving behavior, and (iii) how to deliver information effectively to drivers. In this article, we present a review of previous studies from the UTDrive project attempts to answer above questions.

The process of diffusion bonding in air was successfully used to join 5A90 Al–Mg–Li alloy, which can greatly reduce the welding cycle and equipment requirements. Before diffusion bonding, the Cu nano-coating prepared on the surface of Al–Mg–Li alloy by ultrasonic electrodeposition was used as interlayer to hinder the formation of oxide film and increase the atomic diffusion. The effects of coating thickness, diffusion temperature and interlayer types on the microstructure and performance of joints were investigated. When the diffusion temperature was 530 °C and the coating thickness was 5.12 μm, the optimal shear strength of the joint with 1 μm-thick diffusing interface was 187.9 MPa, which was 90.6% of that in base metal. As the decomposition of unstable Li20Mg6Cu13Al42, Cu atoms diffused into the Al matrix to precipitate Al6CuMg4, and enhanced nano-MgO phase was formed in situ. In addition, the element diffusion behavior and formation mechanisms of the joints were discussed in detail.

Shikonin, a botanical drug extracted from Lithospermum erythrorhizon, exhibits anti-cancer effects in various cancer cell lines. However, the mechanisms underlying these effects have not been completely elucidated yet. Here, we showed that Shikonin induces apoptosis and autophagy in A375 cells and inhibits their proliferation. Shikonin caused G2/M phase arrest through upregulation of p21 and downregulation of cyclin B1. Shikonin significantly triggered ER stress-mediated apoptosis by upregulating the expression of p-eIF2α, CHOP, and cleaved caspase-3. It also induced protective autophagy by activating the p38 pathway, followed by an increase in the levels of p-p38, LC3B-II, and Beclin 1. Upon suppression of autophagy by 3-methyladenine, Shikonin-induced apoptosis was enhanced in A375 cells. Moreover, after pretreatment with N-acetyl-cysteine, Shikonin increased the production of reactive oxygen species that are involved in regulating ER stress-mediated apoptosis and p38-activated autophagy, as evidenced by the reversion of cell viability and apoptosis and a decrease in p-eIF2α, CHOP, p-p38, LC3B-II, and Beclin 1 levels. Thus, we demonstrated that Shikonin induced apoptosis and autophagy in A375 cells via the activation of ROS-mediated ER stress and p38 pathways, indicating that Shikonin can serve as a potential agent for human melanoma therapy.

Background/Aims: Cancer stem cells (CSCs) are largely responsible for tumor relapse and metastatic behavior. Doublecortin-like kinase 1 (DCLK1) was recently reported to be a biomarker for gastrointestinal CSCs and involved in the epithelial-mesenchymal transition (EMT) and tumor progression. B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi-1) is a crucial regulator of CSC self-renewal, malignant transformation and EMT, and a previous study from our group showed that Bmi-1 is upregulated in pancreatic cancer progression and participates in EMT. However, it remains unclear whether DCLK1 is involved in pancreatic cancer or whether DCLK1 is associated with the altered level of Bmi-1 expression. Methods: The correlation of DCLK1 expression and clinical features of pancreatic cancer was analyzed in 210 paraffin-embedded archived pancreatic cancer specimens by immunohistochemical analysis. The biological effects of DCLK1 siRNA on cells were investigated by examining cell proliferation using a cell counting kit and cell colony assays, cell migration by wound healing assay and cell invasion by Transwell invasion assay. We further investigated the effect of therapeutic siRNA targeting DCLK1 on pancreatic cancer cell growth in vivo. Moreover, the molecular mechanism by which DCLK1 upregulates Bmi-1 expression was explored using real-time PCR, western blotting and Co-immunoprecipitation assay. Results: DCLK1 is overexpressed in pancreatic cancer and is related to metastasis and prognosis. Knockdown of DCLK1 markedly suppressed cell growth in vitro and in vivo and also inhibited the migration and invasion of pancreatic cancer cells. Furthermore, we found that DCLK1 silencing could inhibit EMT in cancer cells via downregulation of Bmi-1 and the mesenchymal markers Snail and Vimentin and upregulation of the epithelial marker E-cadherin. Moreover, high DCLK1 expression in human pancreatic cancer samples was associated with a mesenchymal phenotype and increased cell proliferation. Further co-immunoprecipitation indicated that DCLK1 did not interact with Bmi-1 directly. Conclusion: Our data suggest that upregulation of DCLK1 may contribute to pancreatic cancer metastasis and poor prognosis by increasing Bmi-1 expression indirectly. The findings indicate that inhibiting DCLK1 expression might be a novel strategy for pancreatic cancer therapy.

Transmission mechanisms of the servo drive system are not a pure rigid body, and the existence of the elastic transmission mechanisms will make the system generate mechanical resonance. Aiming at mechanical resonance of the servo drive system, the resonance generation mechanism is analyzed, the four-mass model considering the time-varying meshing stiffness of the gear is established, and the influence of different stiffness parameters on the mechanical resonance of the system is researched in this paper. The composite controller of Model Predictive Control (MPC) with Notch Filter is used to simulate the mechanical resonance suppression of the four-mass servo system considering time-varying meshing stiffness, and it is compared with the mechanical resonance suppression method based on Model Predictive Control. The simulation results show that when the step speed is 200 r/min, the overshoot is reduced from 11.6 r/min to 1.1 r/min, which is reduced by 90.5%. Under the impact load condition, from 10 Nm to 30 Nm, overshoot is reduced from 34.3 r/min to 12.8 r/min, reduced by 62%, and torque oscillation is reduced by 81.5%. Therefore, the composite controller of Model Predictive Control with Notch Filter can suppress the mechanical resonance problem effectively, caused by elastic transmission, and improve the robustness of servo drive system.

Acupuncture is a traditional Chinese medicine treatment that has widely been used to modulate gastrointestinal dysfunction caused by irritable bowel syndrome (IBS) and to alleviate the resulting pain. Recent studies have shown that gastrointestinal dysfunction caused by IBS is associated with dysregulation of the brain's central and peripheral nervous system, while functional magnetic resonance imaging (fMRI) helps explore functional abnormality of the brain. However, previous studies rarely used fMRI to study the correlations between brain functional connection, interaction, or segregation (e.g., network degree and clustering coefficient) and acupuncture stimulation in IBS. To bridge this knowledge gap, we study the changed brain functional connection, interaction, and segregation before and after acupuncture stimulation for diarrhea-dominant IBS (IBS-D) with the help of complex network methods based on fMRI. Our results indicate that the abnormal functional connections (FCs) in the right hippocampus, right superior occipital gyrus, left lingual gyrus, left middle occipital gyrus, and the cerebellum, and abnormal network degree in right middle occipital gyrus, where normal controls are significantly different from IBS-D patients, are improved after acupuncture stimulation. These changed FCs and the network degree before and after acupuncture stimulation have significant correlations with the changed clinical information including IBS symptom severity score (r = −0.54, p = 0.0065) and IBS quality of life (r = 0.426, p = 0.038). We conclude that the changes of the brain functional connection, interaction, and segregation in the hippocampus, middle and superior occipital gyrus, cerebellum, and the lingual gyrus may be related to acupuncture stimulation. The abnormal functional connection, interaction, and segregation in IBS-D may be improved after acupuncture stimulation.

Fifth generation (5G) mobile communication technology can enable novel healthcare applications and augment existing ones. However, 5G-enabled healthcare applications demand diverse technical requirements for radio communication. Knowledge of these requirements is important for developers, network providers, and regulatory authorities in the healthcare sector to facilitate safe and effective healthcare. In this paper, we review, identify, describe, and compare the requirements for communication key performance indicators in relevant healthcare use cases, including remote robotic-assisted surgery, connected ambulance, wearable and implantable devices, and service robotics for assisted living, with a focus on quantitative requirements. We also compare 5G-healthcare requirements with the current state of 5G capabilities. Finally, we identify gaps in the existing literature and highlight considerations for this space.

Titanium alloys used to be welded to gain good joint strength at 920 °C through diffusion bonding. However, due to the heat preservation at high temperatures for a long time, we obtain joints with great bond strength while the mechanical properties of the sheet are lost. In this paper, taking Ti6Al4V alloy as an example, we studied the microstructure of the surface under the different times of surface mechanical attrition treatment (SMAT). In addition, the microstructure and mechanical properties after diffusion bonding at 800 °C-5 MPa-1 h were also conducted. The results show that the shear strength of TC4 alloy welded joint after SMAT treatment is improved, and the maximum shear strength can reach 797.7 MPa, up about 32.4%

The aim of this study was to screen synergistic substances included in existing artificial feeds in order to improve the fertility and survival rate of Harmonia axyridis (Pallas) (Coleoptera: Coccinellidae), an efficient pest predator. To this end, we analyzed the potential effects of glucose and trehalose on the growth, development, and reproduction of H. axyridis and evaluated the effect of three different artificial feeds on the energy stress of H. axyridis. The artificial diets contained fresh pork liver, honey, sucrose, vitamin C, and royal jelly, which was marked it as Diet1. The glucose was added to diet1, which was marked it as diet2, while adding trehalose to diet1 was marked as diet3. The pre-oviposition period of H. axyridis on Diet 1 was slower than that of Diet 2 and Diet 3. Additionally, the spawning quantity and incubation rate of insects on Diet 2 and Diet 3 were significantly higher than that of those on Diet 1. Finally, the larval developmental time on Diet 1 was significantly slower than that of Diet 2 and Diet 3. These results indicate that the addition of an appropriate amount of glucose or trehalose may affect positively the growth, development, and reproduction of H. axyridis. In addition, further studies showed that ATP, amino acids and fatty acids content in the H. axyridis also increased after the addition of the synergistic substance. All these results show that proper adjustment of stored energy anabolic and catabolism is important to maintain the metabolic balance of the insect’s entire life cycle and the addition of glucose or trehalose has a certain effect on the life indicators of H. axyridis.

Objectives: The specific intrinsic network coupling abnormalities in mild traumatic brain injury (mTBI) patients are poorly understood. Our objective is to compare the correlations among the default mode, salience, and central executive networks in patients with mTBI and healthy controls.Methods: This 2-year prospective study included 32 acute mTBI patients and 37 healthy comparisons. We calculated the functional connectivity scores among the default mode, salience, and central executive networks. Then we conducted multilevel correlation analysis to investigate component correlations, global graph, and local functional connectivity changes.Results: Patients with mTBI showed significant increased functional connectivity between the anterior part of the default mode network and the salience network compared with controls (p = 0.013, false discovery rate correction). Hyper-connectivity between the default mode and salience network was significantly positively correlated with the dimensional change card sort score in patients with mTBI (r = 0.40, p = 0.037). The average path length of mTBI patients was significantly higher than that of controls (p = 0.028).Conclusions: Aberrant functional coupling between the default mode and salience networks were identified in acute mTBI patients. Our finding has great potential to improve our understanding of the network architecture of mTBI.

Background: Biomarker-targeted molecular imaging holds promise for early detection of pancreatic cancer. The aim of this study was to design and evaluate a plectin-1 targeted multi-functional nanoparticle probe for pancreatic cancer imaging. Methods: 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-amino(polyethylene glycol) (DSPE-PEG-NH2)-modified superparamagnetic iron oxide (Fe3O4) nanoparticles (SPION) were conjugated with plectin-1 antibody and/or Cy7 to create the multi-functional targeted nanoparticle targeted probe (Plectin-SPION-Cy7) or non-targeted probe (SPION-Cy7). Pancreatic carcinoma cell lines expressing plectin-1 were cultured with the targeted or control probes and then were imaged using confocal laser scanning microscopy and magnetic resonance imaging (MRI). Accumulations of the nanoparticles in pancreatic tumor xenografted mice were determined by MRI and fluorescence imaging. Results: In vitro optical imaging and MRI showed that the targeted nanoparticles were highly accumulated in MIAPaCa2 and XPA-1 carcinoma cells but not in non-carcinoma MIN6 cells, which was further confirmed by Prussian blue staining. In vivo MRI showed a significant T2 signal reduction. Prussian blue staining further confirmed that the plectin-1 targeted nanoparticles were highly accumulated in the tumor mass but not in normal pancreatic tissues, or in the liver and kidney, and few nanoparticles were observed in the tumors of mice injected with SPION-Cy7. Conclusions: Our data demonstrate that plectin-1 targeted fluorescence and MR dual-functional nanoparticle can visualize pancreatic cancer, and it has great potential to be used with various imaging devices for pancreatic cancer detection. Keywords: Pancreatic cancer, Plectin-1, Magnetic resonance imaging, Optical imaging, Nanoparticle

Abstract Background Low-grade fibromyxoid sarcoma (LGFMS) is a distinctive slow growing soft tissue neoplasm, mostly affecting young individuals with no gender difference. It usually arises in deep soft tissue of the lower limbs and trunk, but few cases of LGFMS located in pelvis have been reported. Case presentation We describe the magnetic resonance imaging(MRI) features of LGFMS located in the anterior pelvic wall of a 21-year-old female and correlate them with clinicopathological features. The tumor was completely resected and there is no recidivism during the follow-up one year. Conclusions We report on the radiological findings of LGFMS with histological correlation. Awareness of the imaging features may be useful for the diagnosis of LGFMS and helpful to distinguish among mimics.

A five-zone describing model for extrusion of aluminum/copper clad composite was established. Stress and strain were also analyzed by finite element method. The distribution rules of grain size were researched by critical shear strain theory, and zoning phenomenon of grain size was discovered. The grain size of deformed aluminum material becomes gradually finer from center to the interface. The grain size is much fine and the critical shear strain reaches the maximum value in the interface. The grain size of copper material reduces gradually from center to both the interface and exterior surface, which is caused by the higher value of critical shear strain in the interface and exterior surface. The analysis results were verified by microstructure observation and mechanical properties test, indicating that the distribution of grain size for cold extrusion forming can be interpreted by critical shear strain theory.

BACKGROUND AND PURPOSE:Imaging studies of traumatic brain injury demonstrate that the cerebellum is often affected. We aim to examine fractional anisotropy alteration in acute-phase mild traumatic brain injury patients in cerebellum-related white matter tracts. MATERIALS AND METHODS:This prospective study included 47 mild traumatic brain injury patients in the acute stage and 37 controls. MR imaging and neurocognitive tests were performed in patients within 7 days of injury. White matter integrity was examined by using diffusion tensor imaging. We used three approaches, tract-based spatial statistics, graphical-model-based multivariate analysis, and region-of-interest analysis, to detect altered cerebellar white matter integrity in mild traumatic brain injury patients. RESULTS:Results from three analysis methods were in accordance with each other, and suggested fractional anisotropy in the middle cerebellar peduncle and the pontine crossing tract was changed in the acute-phase mild traumatic brain injury patients, relative to controls (adjusted p-value < 0.05). Higher fractional anisotropy in the middle cerebellar peduncle was associated with worse performance in the fluid cognition composite (r = -0.289, p-value = 0.037). CONCLUSION:Altered cerebellar fractional anisotropy in acute-phase mild traumatic brain injury patients is localized in specific regions and statistically associated with cognitive deficits detectable on neurocognitive testing.