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Aims: Acute myocardial infarction (MI), caused by acute coronary artery obstruction, is a common cardiovascular event leading to mortality. Nuclear dot protein 52 (NDP52) is an essential selective ...

Monolayer transition metal dichalcogenides (TMDs) have drawn significant attention for their potential applications in electronics and optoelectronics. To achieve consistent electronic properties and high device yield, uniform large monolayer crystals are crucial. In this report, we describe the growth of high-quality and uniform monolayer WSe2 film using chemical vapor deposition on polycrystalline Au substrates. This method allows for the fabrication of continuous large-area WSe2 film with large-size domains. Additionally, a novel transfer-free method is used to fabricate field-effect transistors (FETs) based on the as-grown WSe2. The exceptional metal/semiconductor interfaces achieved through this fabrication method result in monolayer WSe2 FETs with extraordinary electrical performance comparable to those with thermal deposition electrodes, with a high mobility of up to ≈62.95 cm2 V-1 s-1 at room temperature. In addition, the as-fabricated transfer-free devices can maintain their original performance after weeks without obvious device decay. The transfer-free WSe2-based photodetectors exhibit prominent photoresponse with a high photoresponsivity of ~1.7 × 104 A W-1 at Vds = 1 V and Vg = -60 V and a maximum detectivity value of ~1.2 × 1013 Jones. Our study presents a robust pathway for the growth of high-quality monolayer TMDs thin films and large-scale device fabrication.

Introduction: Ubiquitination is involved in many biological processes and its predictive value for prognosis in cervical cancer is still unclear.Methods: To further explore the predictive value of the ubiquitination-related genes we obtained URGs from the Ubiquitin and Ubiquitin-like Conjugation Database, analyzed datasets from The Cancer Genome Atlas and Gene Expression Omnibus databases, and then selected differentially expressed ubiquitination-related genes between normal and cancer tissues. Then, DURGs significantly associated with overall survival were selected through univariate Cox regression. Machine learning was further used to select the DURGs. Then, we constructed and validated a reliable prognostic gene signature by multivariate analysis. In addition, we predicted the substrate proteins of the signature genes and did a functional analysis to further understand the molecular biology mechanisms. The study provided new guidelines for evaluating cervical cancer prognosis and also suggested new directions for drug development.Results: By analyzing 1,390 URGs in GEO and TCGA databases, we obtained 175 DURGs. Our results showed 19 DURGs were related to prognosis. Finally, eight DURGs were identified via machine learning to construct the first ubiquitination prognostic gene signature. Patients were stratified into high-risk and low-risk groups and the prognosis was worse in the high-risk group. In addition, these gene protein levels were mostly consistent with their transcript level. According to the functional analysis of substrate proteins, the signature genes may be involved in cancer development through the transcription factor activity and the classical P53 pathway ubiquitination-related signaling pathways. Additionally, 71 small molecular compounds were identified as potential drugs.Conclusion: We systematically studied the influence of ubiquitination-related genes on prognosis in cervical cancer, established a prognostic model through a machine learning algorithm, and verified it. Also, our study provides a new treatment strategy for cervical cancer.

By considering dynamic operational conditions in high-speed railway, this paper focuses on the on-line generation problem of train speed profile with energy-saving. This problem is formulated via the model predictive control framework in a moving-horizon manner, such that the real-time running conditions (e.g., temporary speed restrictions) can be involved in the on-line scheduling process of the train. At each control step, a hybrid scheme combining the energy-efficient and time-optimal train control strategies is proposed to ensure the feasibility of the optimal train control problem within the prediction horizon. The optimal control problem in the horizon is transformed into a multi-phase optimal control problem, which is then solved efficiently on-line using the pseudospectral method. By repeatedly solving the train control problem at each step, the energy-efficient train speed trajectory for the whole trip involving dynamic operational conditions can be obtained on-line. In addition, a delay recovery process is designed to re-schedule the train operation if the delay time during the trip exceeds a given threshold value. Finally, numerical examples using data for a real high-speed railway line are given to demonstrate the effectiveness and robustness of the proposed approach.

BackgroundCopper (Cu) is essential for the functioning of various enzymes involved in important cellular and physiological processes. Although critical for normal cardiac function, excessive accumulation, or deficiency of Cu in the myocardium is detrimental to the heart. Fluctuations in cardiac Cu content have been shown to cause cardiac pathologies and imbalance in systemic Cu metabolism. However, the genetic basis underlying cardiac Cu levels and their effects on heart traits remain to be understood. Representing the largest murine genetic reference population, BXD strains have been widely used to explore genotype-phenotype associations and identify quantitative trait loci (QTL) and candidate genes.MethodsCardiac Cu concentration and heart function in BXD strains were measured, followed by QTL mapping. The candidate genes modulating Cu homeostasis in mice hearts were identified using a multi-criteria scoring/filtering approach.ResultsSignificant correlations were identified between cardiac Cu concentration and left ventricular (LV) internal diameter and volumes at end-diastole and end-systole, demonstrating that the BXDs with higher cardiac Cu levels have larger LV chamber. Conversely, cardiac Cu levels negatively correlated with LV posterior wall thickness, suggesting that lower Cu concentration in the heart is associated with LV hypertrophy. Genetic mapping identified six QTLs containing a total of 217 genes, which were further narrowed down to 21 genes that showed a significant association with cardiac Cu content in mice. Among those, Prex1 and Irx3 are the strongest candidates involved in cardiac Cu modulation.ConclusionCardiac Cu level is significantly correlated with heart chamber size and hypertrophy phenotypes in BXD mice, while being regulated by multiple genes in several QTLs. Prex1 and Irx3 may be involved in modulating Cu metabolism and its downstream effects and warrant further experimental and functional validations.

Additional file 1. The experimental protocols of prevention model and treatment model were presented in Fig. 1A and Fig. 4A, separately.

In this paper, a semantic communication framework for image transmission is developed. In the investigated framework, a set of servers cooperatively transmit images to a set of users utilizing semantic communication techniques. To evaluate the performance of studied semantic communication system, a multimodal metric is proposed to measure the correlation between the extracted semantic information and the original image. To meet the ISS requirement of each user, each server must jointly determine the semantic information to be transmitted and the resource blocks (RBs) used for semantic information transmission. We formulate this problem as an optimization problem aiming to minimize each server's transmission latency while reaching the ISS requirement. To solve this problem, a value decomposition based entropy-maximized multi-agent reinforcement learning (RL) is proposed, which enables servers to coordinate for training and execute RB allocation in a distributed manner to approach to a globally optimal performance with less training iterations. Compared to traditional multi-agent RL, the proposed RL improves the valuable action exploration of servers and the probability of finding a globally optimal RB allocation policy based on local observation. Simulation results show that the proposed algorithm can reduce the transmission delay by up to 16.1% compared to traditional multi-agent RL., Comment: 29 pages, 10 figures

Additional file 2: Fig. S1. The original and unprocessed amplification patterns of PmCG15-009-linked markers YTU103–101 in genotyping resistant parent ShiCG15–009, susceptible parent Yannong 21, and randomly selected F2:3 families of ShiCG15–009 × Yannong 21. Fig. S2. The original and unprocessed amplification patterns of PmCG15–009-linked markers CIT02g–17 in genotyping resistant parent ShiCG15–009, susceptible parent Yannong 21, and randomly selected F2:3 families of ShiCG15–009 × Yannong 21. Fig. S3. The original and unprocessed amplification patterns of PmCG15–009-linked markers CISSR02g-6 in ShiCG15–009, Yannong 21 and 15 wheat cultivars/lines susceptible to powdery mildew. Fig. S4. The original and unprocessed amplification patterns of PmCG15–009-linked markers CIT02g-17 in ShiCG15–009, Yannong 21 and 15 wheat cultivars/lines susceptible to powdery mildew.

BackgroundThe left atrial low-voltage areas (LVAs) are associated with atrial fibrosis; however, it is not clear how the left atrial LVAs affect the recurrence of arrhythmias after catheter ablation, and the efficacy and safety of the left atrial substrate modification based on LVAs as a strategy for catheter ablation of atrial fibrillation (AF) are not evident for AF patients with LVAs.MethodsWe performed a systematic search to compare the arrhythmia recurrence in AF patients with and without LVAs after conventional ablation and arrhythmia recurrence in LVAs patients after conventional ablation with and without substrate modification based on LVAs.ResultA total of 6 studies were included, involving 1,175 patients. The arrhythmia recurrence was higher in LVA patients after conventional ablation (OR: 5.14, 95% CI: [3.11, 8.49]; P < 0.00001). Additional LVAs substrate modification could improve the freedom of arrhythmia in LVAs patients after the first procedure (OR: 0.30, 95% CI: [0.15, 0.62]; P = 0.0009). However, there was no significant difference after multiple procedures (P = 0.19). The procedure time (MD: 26.61, 95% CI [15.79, 37.42]; P < 0.00001) and fluoroscopy time (MD: 6.90, 95% CI [4.34, 9.47]; P < 0.00001) in LVAs patients with additional LVAs substrate modification were significantly increased compared to LVAs patients’ without substrate modification. Nevertheless, there were no higher LVAs substrate modification-related complications (P = 0.93) between LVAs patients with and without additional LVAs substrate modification. In the subgroup analysis, the additional LVAs substrate modification reduced the risk of arrhythmia recurrence in LVAs patients during the follow-up time, which was 12 months (OR: 0.32, 95% CI (0.17, 0.58); P = 0.002), and box isolation (OR: 0.37, 95% CI (0.20, 0.69); P = 0.002) subgroups, but the type of AF, follow up >12 months and homogenization subgroups were not statistically significant. Trial sequential analysis shows conclusive evidence for the LVAs ablation.ConclusionThis study has shown that LVAs could improve the risk of arrhythmia recurrence in AF patients after conventional ablation. And additional LVAs substrate modification after conventional ablation could increase the freedom of arrhythmia recurrence in LVAs patients. Interestingly, the box isolation approach appeared more promising.Systematic review registration[http://www.crd.york.ac.uk/prospero], identifier [CRD42021239277].

Modern electronics demand transistors with extremely high performance and energy efficiency. Charge-based transistors with conventional semiconductors experience substantial heat dissipation because of carrier scattering. Here, we demonstrate low-loss topological phase change transistors (TPCTs) based on tellurium, a Weyl semiconductor. By modulating the energy separation between the Fermi level and the Weyl point of tellurium through electrostatic gate modulation, the device exhibits topological phase change between Weyl (Chern number ≠ 0) and conventional (Chern number = 0) semiconductors. In the Weyl ON state, the device has low-loss transport characteristics due to the global topology of gauge fields against external perturbations; the OFF state exhibits trivial charge transport in the conventional phase by moving the Fermi level into the bandgap. The TPCTs show a high ON/OFF ratio (10 8 ) at low operation voltage (≤2 volts) and high ON-state conductance (39 mS/μm). Our studies provide alternative strategies for realizing ultralow power electronics.

Epilepsy is a common pediatric disease that often leads to cognitive and intellectual impairments. Here, we explore the reorganized functional networks in children and adolescents with focal epilepsy (CAFE) and analyze the relationship between network reorganization and intellectual deficits to reveal the underlying link between them.Fifty-four CAFE (6-16 years old; right-handed) and 42 well-matched healthy controls were recruited. Subjects underwent resting-state functional magnetic resonance imaging, and functional networks were analyzed by graph analysis. Intelligence testing (Wechsler Intelligence Scale for Children-Chinese revision) included measures for verbal IQ (VIQ), performance IQ, and full-scale IQ.(1) In the CAFE compared with the healthy controls, (a) the local efficiency, clustering coefficient and standardized clustering coefficient were significantly decreased (p0.05); (b) the degree centrality and nodal efficiency of the left precentral gyrus (LPG) were significantly increased (p0.05, Bonferroni correction), and the nodal shortest path length was significantly decreased (p0.05, Bonferroni correction); and (c) functional connectivity of the LPG with the bilateral inferior frontal ventral gyrus, right lateral superior occipital gyrus, left middle occipital gyrus, bilateral superior parietal lobule, right anterior prefrontal cortex, and bilateral cerebellum was enhanced (p0.05,GRF correction), while functional connectivity with the bilateral superior temporal gyrus was decreased (p0.05, GRF correction). (2) The nodal shortest path length of the LPG in CAFE was associated with full-scale IQ, performance IQ, and VIQ, and local efficiency was associated with VIQ.Our results showed that the middle LPG in CAFE undergoes network reorganization that positively influences intelligence. Differences in local efficiency of functional networks in children and early adolescents have a significant effect on intelligence.

In recent years, the Yushu Museum has conducted a systematic investigation on the rock art of the Tongtian River Basin in its prefecture and newly discovered 1230 panels’ rock art (more than 1700 images). This paper is a statistical and comparative analysis of the newly discovered rock art. According to content and production techniques, we divided the rock art of the Tongtian River Basin into two big areas. The West Area is the upper part of the river basin, which is the area above the confluence of Tongtian River and Chumar River (Qumalai River); the East Area is the lower part of the river basin, which is from the confluence to the Batang estuary of Yushu. This area can be subdivided into three subareas. The majority of the Tongtian River Basin’s rock art is categorized as animal type. Yak and deer are respectively the main themes of the West Area and the East Area. In addition, there are other rock art types like symbol, character, pagoda, carriage and so on. The two areas have both commonalities and their own characteristics. Through the typological analysis of production techniques, in the cases of carriage rock art, and deer rock art, we think that the rock art mainly used the whole-image chiseling technique. This technique can be traced back to the Shang Dynasty; the rock art mainly chiseled linearly is dated to the early Zhou Dynasty to the Warring States Period; the rock art that was creates with the line carving technique is dated to the Warring States Period to the Western Han Dynasty; the rock art that was creates with the grind carving technique can be dated back to the Qin and Han dynasties; and the rock art mainly used scratching technique can be traced back to the Ancient Tibetan Empire Period (618-842 AD)

BackgroundEntrustable professional activities (EPAs) were first introduced by Olle ten Cate in 2005. Since then, hundreds of applications in medical research have been reported worldwide. However, few studies discuss the use of EPAs for residency training in pediatric intensive care medicine. We conducted a pilot study of EPA for pediatric intensive care medicine to evaluate the use of EPAs in this subspecialty.Materials and MethodsA cross-sectional study was implemented in pediatric intensive care medicine standardized residency training at the Qilu Hospital of Shandong University. An electronic survey assessing EPA performance using eight scales composed of 15 categories were distributed among residents and directors.ResultsA total of 217 director-assessment and 44 residents’ self-assessment questionnaires were collected, both demonstrating a rising trend in scores across postgraduate years. There were significant differences in PGY1-vs.-PGY2 and PGY1-vs.-PGY3 director-assessment scores, while there were no differences in PGY2-vs.-PGY3 scores. PGY had a significant effect on the score of each EPA, while position significantly affected the scores of all EPAs except for EPA1 (Admit a patient) and EPA2 (Select and interpret auxiliary examinations). Gender only significantly affected the scores of EPA6 (Report a case), EPA12 (Perform health education), and EPA13 (Inform bad news).ConclusionThis study indicates that EPA assessments have a certain discriminating capability among different PGYs in Chinese standardized residency training in pediatric intensive care medicine. Postgraduate year, gender, and resident position affected EPA scores to a certain extent. Given the inconsistency between resident-assessed and director-assessed scores, an improved feedback program is needed in the future.

PurposeLong noncoding RNAs (LncRNAs) play complex but important roles in the progression of various tumors. This study aimed to elucidate the functional mechanisms of the HLA complex group 11 (HCG11) in nasopharyngeal carcinoma (NPC).Patients and MethodsHCG11 levels in NPC specimens were determined by fluorescence in situ hybridization (FISH) and qPCR. Proliferation, apoptosis, and metastasis of NPC cells were determined using CCK8, colony formation, annexin V-PI, and transwell assays. A murine tumor xenograft model was used to investigate the regulatory function of HCG11 in NPC in vivo, and immunohistochemical staining was used to determine the Ki-67 level in tumors. The target relationships between HCG11, microRNA miR-490-3p, and MAPK kinase kinase 9 (MAP3K9) were detected using bioinformatics, qPCR, western blotting, and luciferase reporter assays.ResultsHCG11 was highly expressed in NPC tissues and was positively associated with tumor stage, lymphatic metastasis, and poor prognosis. Functionally, HCG11 knockdown inhibited proliferation and migration and induced apoptosis of NPC cells. Mechanistically, miR-490-3p is a direct target of HCG11, oncogenic functions of HCG11 in NPC cell proliferation and migration can be partially reversed by the miR-490-3p inhibitor. HCG11 significantly increased mitogen-activated protein kinase MAPK kinase 9 (MAP3K9) levels by inhibiting miR-490-3p.ConclusionHCG11 facilitates NPC progression via MAP3K9 signaling by sponging miRNA-490-3p, which may contribute to new prognostic markers and promising therapeutic targets.

Second-hand smoking evokes inflammation and cardiovascular diseases. Recent evidence has revealed a pivotal role for deranged autophagy in smoke exposure-induced cardiac anomalies. This study evaluated the impact of haploinsufficiency of the mTOR-independent autophagy protein Beclin1 on side-stream smoke exposure-induced cardiac anomalies and mechanism(s) involved. Adult WT and Beclin1 haploinsufficiency (Becn+/−) mice were exposed to cigarette smoke for 1 h daily for 90 days. Echocardiographic, cardiomyocyte function, intracellular Ca2+, autophagy, mitophagy, apoptosis and inflammation were examined. DHE staining was employed to evaluate O2− level. Our data revealed that Beclin1 deficiency exacerbated smoke exposure-induced myocardial anomalies in geometry, fractional shortening, cardiomyocyte function, intracellular Ca2+ handling, TEM ultrastructure, and inflammation along with pronounced apoptosis and O2− production. Side-stream smoke provoked excessive autophagy/mitophagy, mtDNA release, and activation of innate immune response signals cyclic GMP-AMP synthase (cGAS) and its effector – stimulator of interferon genes (STING), the effect was abolished or unaffected by Becn haploinsufficiency. STING phosphorylation was overtly promoted by smoke exposure in Becn+/− mice. Smoke exposure also suppressed phosphorylation of mTOR although it facilitated that of ULK1 in both groups. In vitro data revealed that inhibition of cGAS or STING failed to affect smoke extract-induced mitophagy although they abrogated smoke extract-induced cardiomyocyte dysfunction except cGAS inhibition in Becn+/− mice. These data suggest that Beclin1 is integral in the maintenance of cardiac homeostasis under side-stream smoke exposure via a STING-mediated mechanism.

Supplemental Document

Additional file 4: Table S2. The cis-acting elements of PvHsfs.

Additional file 3: Table S1. Identification of PvHsf members in P. vulgaris.

Additional file 1.

Additional file 6.

Additional file 6: Table S4. The database and software websites.

This paper proposes a new method that fuses acoustic measurements in the reverberation field and low-accuracy inertial measurement unit (IMU) motion reports for simultaneous localization and mapping (SLAM). Different from existing studies that only use acoustic data for direction-of-arrival (DoA) estimates, the source's distance from sensors is calculated with the direct-to-reverberant energy ratio (DRR) and applied as a new constraint to eliminate the nonlinear noise from motion reports. A particle filter is applied to estimate the critical distance, which is key for associating the source's distance with the DRR. A keyframe method is used to eliminate the deviation of the source position estimation toward the robot. The proposed DoA-DRR acoustic SLAM (D-D SLAM) is designed for three-dimensional motion and is suitable for most robots. The method is the first acoustic SLAM algorithm that has been validated on a real-world indoor scene dataset that contains only acoustic data and IMU measurements. Compared with previous methods, D-D SLAM has acceptable performance in locating the robot and building a source map from a real-world indoor dataset. The average location accuracy is 0.48 m, while the source position error converges to less than 0.25 m within 2.8 s. These results prove the effectiveness of D-D SLAM in real-world indoor scenes, which may be especially useful in search and rescue missions after disasters where the environment is foggy, i.e., unsuitable for light or laser irradiation.

Additional file 1: Figure S1. SNAP25 expression was associated with tumor purity as well as several immune cell types within different tumors. These included CD8+ T cells, CD4+ T cells, macrophages, B cells, neutrophils, and dendritic cells.

Additional file 7: Table S5. QRT-PCR primer of PvHsfs designed by Primer premier 5.0 software.

Additional file 6.

Xin He,1 Jiping Sun,2 Chao Liu,2 Xiaoyang Yu,2 Huixian Li,2 Wenjing Zhang,2 Yan Li,2 Yingzhou Geng,2 Zhigang Wang2 1Dialysis Department of Nephrology Hospital, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China; 2Department of Nephrology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of ChinaCorrespondence: Zhigang Wang, First Affiliated Hospital of Xi’an Jiaotong University, West Yanta Road 277, Xi’an, 710061, People’s Republic of China, Email wangzhigang2017@xjtu.edu.cnPurpose: Emerging evidence has revealed that gut microbiota plays a pivotal role in the pathogenesis of type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD). However, few studies have used metagenomic sequencing to analyze the alterations of gut microbiota community in patients with early-stage DKD.Methods: We carried out metagenomic sequencing in fecal samples of 10 DKD patients (DKD group) and 10 T2DM patients who appeared to be less prone to DKD (non-DKD group), aiming to compare the composition and function of gut microbiota between the DKD and non-DKD groups.Results: The gut microbial community of the DKD group was significantly different from that of the non-DKD group, characterized by a marked increase in phylum Proteobacteria, genus Selenomonadales, Neosynechococcus, Shigella, Bilophila, Acidaminococcus, species, Escherichia coli, Bacteroides plebeius, Megasphaera elsdenii, Acidaminococcus unclassified, and Bilophila wadsworthia. The amounts of species Citrobacter farmeri and Syntrophaceticus schinkii were significantly and positively correlated with the urinary albumin creatinine ratio in the DKD group. Furthermore, functional analysis based on dbCAN and KEGG databases showed aberrant lipopolysaccharide (LPS) biosynthesis and carbohydrate metabolism in the gut microbiome of the DKD group.Conclusion: Our findings provided evidence for alterations in the composition and function of gut microbiota in patients with DKD versus the non-DKD group. These data may contribute to a more comprehensive understanding of the pathological mechanisms of DKD.Keywords: diabetic kidney disease, gut microbiota, metagenomics, type 2 diabetes mellitus

This paper develops a hybrid Copula–Bayesian-based approach to model the structural health of an operational metro tunnel in a dependent system, where risk factors interact with each other. Aiming to rectify drawbacks of discrete Bayesian networks, the Gaussian copula and different marginal distributions are involved to build up complicated interactions among possible risk factors and structural health state more precisely and rationally. To achieve systematic and real-time decision support for safety insurance during the entire life cycle of risk-prone systems, model analytics is conducted to perform correlation analysis, forward reasoning, and backward reasoning. For demonstrating the effectiveness of the method, it is applied to a realistic cross-river tunnel, the Wuhan Yangtze Metro Tunnel in China, where all the concerning risk factors are water-related rooting in water leakage, poor construction quality, exterior load, and others. Due to the availability of vault displacement by sensors, it can herein represent the structural health to explore the impacts of risk factors. Larger vault displacement implies higher risk in the overall safety condition of the tunnel structure. This research contributes to (a) the state of knowledge by integrating Bayesian networks with copula, contributing to a more robust risk assessment by accurately modeling the complex dependence structure of risk factors; (b) the state of practice by providing guidelines of the whole-life-cycle safety control for complex systems under uncertainty and randomness, which not only prevent structural failure in advance but also control risk after accident occurrence.

The tensile properties and microstructure evolution of Cu–0.2Cr–0.08Zr alloy during high temperature tensile process were investigated. The results showed that with the test temperature increasing, both strength and elongation decreases slowly, the addition of Zr can improve the high temperature properties due to the small precipitates in the matrix. The high temperature fracture mechanism of this alloy was ductile fracture. With the test temperature increasing, the reduction of area decreased, less shallow dimples and more large voids can be observed on the fracture surface of sample.

Additional file 4: Table S4. Risk factor associated disease progression in COVID-19 patients in univariate Cox regression analysis.

Additional file 5: Table S5. Collinearity diagnosticsof variables in multivariate analysis.

Additional file 1: Table S1. Upper and lower limits of kidney function laboratory parameters in male and female patients with COVID-19.

Additional file 6: Table S6.Associations of kidney function indexes with disease progression in COVID-19 patients by multivariate cox regression analyses.

Additional file 2: Table S2. Risk factors associated with disease progression in COVID-19 patients in univariate Cox regression analysis.

Additional file 1: Figure S1. Biocompatibility of electroactive hydrogel. Scale bar = 200 μm.

Additional file 3: Table S3. Summary and comparison of recent studies on kidney damage from COVID-19 patients.

Purpose Growing evidence indicates that aberrant expression of microRNAs contributes to tumor development. However, the biological role of microRNA-4490 (miR-4490) in gastric cancer (GC) remains to be clarified. Methods To explore the function of miR-4490 in GC, we performed colony formation, EdU incorporation, qRT-PCR, Western blotting, in situ hybridization (ISH), immunohistochemistry (IHC), flow cytometry, ChIP and dual-luciferase reporter assays. In addition, the growth, migration and invasion capacities of GC cells were evaluated. Results We found that miR-4490 was significantly downregulated in primary GC samples and in GC-derived cell lines compared with normal controls, and that this expression level was negatively correlated with GC malignancy. Exogenous miR-4490 expression not only reduced cell cycle progression and proliferation, but also significantly inhibited GC cell migration, invasion and epithelial-mesenchymal transition (EMT) in vitro. Mechanistically, we found that miR-4490 directly targets USP22, which mediates inhibition of GC cell proliferation and EMT-induced metastasis in vitro and in vivo. Moreover, we found through luciferase and ChIP assays that transcription factor POU2F1 can directly bind to POU2F1 binding sites within the miR-4490 and USP22 promoters and, by doing so, modulate their transcription. Spearman’s correlation analysis revealed a positive correlation between USP22 and POU2F1 expression and negative correlations between miR-4490 and USP22 as well as miR-4490 and POU2F1 expression in primary GC tissues. Conclusion Based on our results we conclude that miR-4490 acts as a tumor suppressor, and that the POU2F1/miR-4490/USP22 axis plays an important role in the regulation of growth, invasion and EMT of GC cells. Electronic supplementary material The online version of this article (10.1007/s13402-020-00553-1) contains supplementary material, which is available to authorized users.

The maglev transportation system has obvious advantages in safety, reliability, and energy efficiency compared with other rail transit systems with the same carrying capacity. Research topics concerning optimal operations for maglev trains have attracted much attention in recent years. Since the basic resistance acting on the maglev train is more complex than that on the conventional train, it is more challenging to solve the time-optimal and energy-optimal problems, especially considering the operational and safety constraints, such as fluctuating track gradients, varying speed limits, and speed-dependent control bound constraints. This paper considers the time-optimal control problem for medium-speed maglev trains with operational and safety constraints. By expressing the basic resistance of the medium-speed maglev train as a piecewise-quadratic function of the train’s speed, we formulate the time-optimal control problem as an optimal switching control problem with free terminal time and state-dependent switching conditions. To solve this problem, we first transform the optimal switching control problem with free terminal time into one with fixed terminal time. Then, we introduce a binary-valued function to govern the switching condition, and further replace the binary constraints with equivalent continuous constraints. The resulting optimal control problem is converted into a finite-dimensional optimization problem by applying the control parameterization and time-scaling transformation techniques. The speed limit and speed-dependent control bound constraints are then transformed into a set of point and integral constraints. Furthermore, the equivalent continuous constraints involving the binary-valued function are tackled using the exact penalty method. Finally, we obtain a nonlinear programming problem which can be solved using gradient-based optimization algorithms. A numerical example using data for a real line is given to demonstrate the effectiveness of the proposed approach.

Tight sandstone reservoir evaluation and characterization faced great challenge by using conventional well logging data due to the complicated pore structure. To improve tight sandstone reservoir identification, the pore structure should be first characterized. In this study, using the tight Chang 8 Formation of Pengyang Region, west Ordos Basin as an example, 20 core samples were drilled for laboratory nuclear magnetic resonance (NMR) and mercury injection capillary pressure (MICP) experiments. A model, which was used to construct capillary pressure (Pc) curves from NMR data, was proposed, and the corresponding models were established based on classified power function (CPF) method to classify formations into three types. Based on these relationships, the NMR T2 distributions were transformed as pseudo Pc curves and pore throat radius distributions. After these relationships were extended into field applications, consecutive pseudo Pc curves were acquired, and the pore structure evaluation parameters and permeability were also predicted. Comparisons of predicted parameters with core-derived results illustrated the reliability of our proposed model and method.

Objective Human uveal melanoma (UM) is a common ocular malignant tumor with a high risk of metastasis. Emerging evidence indicates that long non-coding RNAs (lncRNAs) are correlated with the development of UM. Here, we aimed to determine the biological significance of lncRNA growth arrest-specific transcript 5 (GAS5) in UM. Methods The expression levels of GAS5 and microRNA-21 (miR-21) in UM tissues and cells were detected by qRT-PCR analysis. CCK-8 assay was performed to investigate the viability of UM cells after cell transfections, and the migration and invasion of UM cells were determined by transwell assay. The protein expression levels were detected by Western blot assay. The relationship between miR-21 and GAS5 in UM cells was confirmed by bioinformatics prediction and luciferase report assay. Results Our experiments demonstrated that GAS5 was markedly downregulated in UM cells and clinical specimens. Overexpression of GAS5 inhibited, whereas knockdown of GAS5 promoted the viability, migration, and invasion of UM cells. The epithelial-to-mesenchymal transition (EMT) process of UM cells was also suppressed by upregulating of GAS5 and enhanced by downregulating of GAS5. Additionally, as a competitive endogenous RNA (ceRNA), GAS5 directly binded to the oncogenic miR-21 in UM cells, and overexpression of miR-21 attenuated the EMT-suppressing effect of GAS5. Conclusion Taken together, our findings suggest that GAS5/miR-21 axis is implicated in the pathogenesis of UM and might serve as a potential therapeutic target.