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Abstract High‐throughput sequencing methods have facilitated the identification of novel selenoproteins, which exert a vital role in the development and progression of tumor diseases. Recently, Selenoprotein M (SELM) is upregulated in several types of cancer. However, the biological roles of SELM in renal cell carcinoma (RCC) remain unclear. In this paper, quantitative reverse transcription PCR (qRT‐PCR) and Western blot were used to measure relative levels of SELM in a cohort of RCC tissues with matched normal tissues as well as human RCC cell lines. SELM expression was found to be upregulated in RCC. High level of SELM was related to poor prognosis of RCC. Furthermore, silence of SELM could inhibit the in vitro proliferative, migratory, and invasive capacities of RCC. In addition, downregulated SELM could impede in vivo tumorigenesis of RCC. SELM could activate the PI3K/Akt/mTOR pathway and mediate expressions of matrix metallopeptidase 2 and 9 (MMP2, MMP9). In conclusion, our study reveals the oncogenic function of SELM in RCC, and SELM may be a therapeutic and prognostic target for RCC.

Fault detection is quite important for discrete event systems. We investigate K-codiagnosability of Petri nets in this paper under the framework that some local sites monitor the operation of the system using their own masks. They exchange information with a coordinator while do not communicate with each other. A fault is detected when there exists a site can diagnose it. We recall the notion of Modified Verifier Nets (MVNs), and prove that K-codiagnosability can be verified looking at some special cycles in the reachability or coverability graph of the MVN. In particular, the proposed approach is available for bounded and unbounded nets. Finally, we give an algorithm to compute the minimum value of K.

Mobile robots are extensively used to complete repetitive operations in industrial areas such as intelligent transportation, logistics, and manufacturing systems. This paper addresses the path planning problem of multi-type robot systems with time windows based on timed colored Petri nets. The tasks to be completed are divided into three different types: common, exclusive and collaborative. An analytical approach to plan a group of different types of mobile robots is developed to ensure that some specific robots will visit task regions within given time windows. First, a multi-type robot system and its environment are modeled by a timed colored Petri net. Then, some methods are developed to convert the task requirements that contain logic constraints and time windows into linear constraints. Based on integer linear programming techniques, a planning approach is proposed to minimize the total cost (i.e., total travel distance) of the system. Finally, simulation studies are investigated to show the effectiveness of the developed approach.

The automated manufacturing systems (AMS) can be regarded as a resource allocation system which can be abstracted as discrete event systems (DES) for analysis. Once an effective computational method is put forward to the DES, the corresponding real AMS, connected by networks or sensors, can be indirectly controlled. Supervisory control theory (SCT) of DES is developed with the intention of discovering the maximally permissible supervisor of AMS. The state-tree structure (STS) is an extension of SCT, whose application is mainly to solve the SCT state explosion of complicated AMS. The nonblocking supervisory control is investigated on the foundation of predicates in STS, of which the synthesis focuses on the states of the system but ignores the transition between events. In order to effectively solve the above problems, this paper puts forward a novel method based on state feedback control (SFBC) in the STS framework, by which the relation among events is discussed. First, following the definition of the SFBC for predicates, the algorithms to compute the SFBC under reachability, coreachability, and weak controllability are introduced. Second, it is proved that the nonblocking SFBC obtained by the proposed algorithm is equivalent to the one by computing predicates first, which ensures the satisfactory controllers for the supervisory control problems. To demonstrate the contribution of the proposed approach, which is designed considering the symmetry of the system behavior between the real system and its STS model, three examples are illustrated.

Background Although several studies have focused on the associations between particle size and constituents and blood pressure, results have been inconsistent. Methods and Results We conducted a panel study, between December 2017 and January 2018, in 88 healthy university students in Guangzhou, China. Weekly systolic blood pressure and diastolic blood pressure were measured for each participant for 5 consecutive weeks, resulting in a total of 440 visits. Mass concentrations of particles with an aerodynamic diameter of ≤2.5 µm (PM2.5), ≤1.0 µm (PM1.0), ≤0.5 µm (PM0.5), ≤0.2 µm (PM0.2), and number concentrations of airborne particulates of diameter ≤0.1 μm were measured. Linear mixed‐effect models were used to estimate the associations between blood pressure and particles and PM2.5 constituents 0 to 48 hours before blood pressure measurement. PM of all the fractions in the 0.2‐ to 2.5‐μm range were positively associated with systolic blood pressure in the first 24 hours, with the percent changes of effect estimates ranging from 3.5% to 8.8% for an interquartile range increment of PM. PM0.2 was also positively associated with diastolic blood pressure, with an increase of 5.9% (95% CI, 1.0%–11.0%) for an interquartile range increment (5.8 μg/m3) at lag 0 to 24 hours. For PM2.5 constituents, we found positive associations between chloride and diastolic blood pressure (1.7% [95% CI, 0.1%–3.3%]), and negative associations between vanadium and diastolic blood pressure (−1.6% [95% CI, −3.0% to −0.1%]). Conclusions Both particle size and constituent exposure are significantly associated with blood pressure in the first 24 hours following exposure in healthy Chinese adults.

Transgenic crops producing Bacillus thuringiensis (Bt) insecticidal proteins are grown widely for pest control, but the evolution of resistance in target pests could reduce their efficacy. Mutations in genes encoding cadherin, ABC transporter or tetraspanin were linked with resistance to Cry1Ac in several lepidopteran insects, including the cotton bollworm (Helicoverpa armigera), a worldwide agricultural pest. However, the detailed molecular mechanisms by which these mutations confer insect resistance to Cry1Ac remain largely unknown. In this study, we analyzed the midgut transcriptomes of a susceptible SCD strain and three SCD-derived Cry1Ac-resistant strains of H. armigera (SCD-r1, with a naturally occurring deletion mutation of cadherin; SCD-KI, with a knock-in T92C point mutation in tetraspanin; and C2/3-KO, with both ABCC2 and ABCC3 knocked out). Evaluation of midgut transcript profiles of the four strains without Cry1Ac exposure identified many constitutively differentially expressed genes (DEGs) in the resistant SCD-r1 (n = 1355), SCD-KI (n = 1254) and C2/3-KO (n = 2055) strains. Analysis of DEGs in the midguts of each strain after Cry1Ac exposure revealed similar patterns of response to Cry1Ac in the SCD and SCD-r1 strains, but unique responses in the SCD-KI and C2/3-KO strains. Expression of midgut epithelium healing and defense-related genes was strongly induced by Cry1Ac intoxication in the SCD and SCD-r1 strains, while immune-related pattern recognition receptor and effector genes were highly expressed in the SCD-KI strain after Cry1Ac exposure. This study advances our knowledge of the transcriptomic basis for insect resistance to Bt toxins and provides a valuable resource for further molecular characterization of insect response to Cry1Ac toxin in H. armigera and other pest species.

Automated guided vehicles (AGVs) are extensively used in many applications such as intelligent transportation, logistics, and industrial factories. In this paper, we address the path planning problem for an AGV system (i.e. a team of identical AGVs) with logic and time constraints using Petri nets. We propose a method to model an AGV system and its static environment by timed Petri nets. Combining the structural characteristics of Petri nets and integer linear programming technique, a path planning method is developed to ensure that all task regions are visited by AGVs in time and forbidden regions are always avoided. Finally, simulation studies are presented to show the effectiveness of the proposed path planning methodology.

Lung adenocarcinoma accounts for half of all lung cancer cases in most countries. Mounting evidence has demonstrated that microRNAs play important roles in cancer progression, and some of them can be identified as potential biomarkers. This study aimed to explore the role of miR-550a-5p, a lung adenocarcinoma-associated mature microRNA screened out from the TCGA database via R-studio and Perl, with abundant expression in samples and with 5-year survival prognosis difference, as well as having not been studied in lung cancer yet. Potential target genes were predicted by the online database. Gene ontology enrichment, pathway enrichment, protein–protein interaction network, and hub genes–microRNA network were constructed by FunRich, STRING database, and Cytoscape. Then, LIMD1, a known tumor suppressor gene reported by multiple articles, was found to have a negative correlation with miR-550a-5p. The expression of miR-550a-5p was up-regulated in tumor samples and tumor-associated cell lines. Its high expression was also correlated with tumor size. Cell line A549 treated with miR-550a-5p overexpression promoted tumor proliferation, while H1299 treated with miR-550a-5p knockdown showed the opposite result. Mechanically, miR-550a-5p negatively regulated LIMD1 by directly binding to its 3′-UTR validated by dual luciferase assay. In summary, a new potential prognostic and therapeutic biomarker, miR-550a-5p, has been identified by bioinformatics analysis and experimental validation in vitro and in vivo, which promotes lung adenocarcinoma by silencing a known suppressor oncogene LIMD1.

Hypoxia and ischemia are the main underlying pathogenesis of stroke and other neurological disorders. Cerebral hypoxia and/or ischemia (e.g., stroke) can lead to neuronal injury/death and eventually cause serious neurological disorders or even death in the patients. Despite knowing these serious consequences, there are limited neuroprotective strategies against hypoxic and ischemic insults in clinical settings. Recent studies indicate that microRNAs (miRNAs) are of great importance in regulating cerebral responses to hypoxic/ischemic stress in addition to the neuroprotective effect of the δ-opioid receptor (DOR). Moreover, new discovery shows that DOR can regulate miRNA expression and inhibit inflammatory responses to hypoxia/ischemia. We, therefore, summarize available data in current literature regarding the role of DOR and miRNAs in regulating the neuroinflammatory responses in this article. In particular, we focus on microglia activation, cytokine production, and the relevant signaling pathways triggered by cerebral hypoxia/ischemia. The intent of this review article is to provide a novel clue for developing new strategies against neuroinflammatory injury resulting from cerebral hypoxia/ischemia.

Transcranial magnetic stimulation (TMS) has been widely used in scientific research and clinical application. In TMS, the stimulation coil generates a focusing induced electrical field in the intracranial target area to achieve neuromodulation. Since different disorders correspond to their specific target areas, in order to avoid non-target tissue being stimulated, the figure-of-eight (FOE) coil with good focusing performance is still the most commonly used magnetic coil. In this paper, the U-shaped coil with multi-parameters is introduced and optimized. The spatial distributions of the intracranial induced electrical field produced by the U-shaped coil are obtained using the finite-element method. Compared to the traditional FOE coil, the U-shaped coil not only has a great advantage in improving focalization but also is beneficial to obtain other improved characteristics. The mathematical relationship between the coil geometric parameters and the intracranial induced electrical field characteristics is analyzed under the constraint of fixed coil power loss. To further improve coil efficiency, the particle swarm optimization (PSO) is adopted to optimize the coil parameters. A real human head modeled as homogeneous and isotropic is occupied in this paper to verify our method, and a traditional FOE coil is used as the reference coil. We also checked the maximum induced charge density on the targeted plane generated by the optimized U-shaped coil to make sure that it will not cause induced neurologic damage.

Background/Aims: Mammalian target of rapamycin (mTOR) is a valuable treatment target of renal cell carcinoma (RCC). Palomid 529 is a novel mTORC1/2 dual inhibitor. Methods: RCC cells were treated with different concentrations of Palomid 529. Cell survival was tested by MTT assay and clonogenicity assay. Cell proliferation was tested by BrdU ELISA assay. Cell apoptosis was tested by the Hoechst-33342 nuclei staining assay and Histone DNA ELISA assay. mTOR signaling was tested by Western blotting assay and co-immunoprecipitation (IP) assay. The SCID mouse 786-O xenograft model was established to test RCC cell growth in vivo. Results: Palomid 529 exerted cytotoxic, anti-proliferative and pro-apoptotic activities in 786-O RCC cells. Palomid 529 disassembled mTORC1/2, causing de-phosphorylation of mTORC1/2 substrates. Bromodomain-containing protein 4 (BRD4) is a primary resistant factor of Palomid 529. Palomid 529-induced 786-O cell apoptosis was sensitized by BRD4 inhibitors or BRD4 silencing, but inhibited with BRD4 over-expression. Palomid 529-induced cytotoxicity in the primary human RCC cells was negatively correlated with BRD4 expression level. In vivo, Palomid 529 i.p. administration inhibited 786-O xenograft tumor growth in SCID mice. Its anti-tumor activity was further sensitized by co-administration of the BRD4 inhibitor JQ1. Cconclusion: Palomid 529 inhibits RCC cell growth in vitro and in vivo. BRD4 inhibition could further sensitize Palomid 529 against RCC cells.

Developmental dysplasia of the hip (DDH) is one of the most common congenital disorders in childhood. Its diverse pathological changes require different treatments and result in different outcomes. Although many studies have been conducted on DDH, some special pathology is still unrecognized. We here presented a rare case of a one-year and eleven-month old girl with DDH; a half-free intra-articular osteocartilaginous tissue was found in her right hip joint. X-ray, computer assisted tomography (CT) and magnetic resonance imaging (MRI) were performed to evaluate the pathological changes. MRI revealed some positive findings. The patient experienced open reduction and histopathological examination of the small tissue. Through gross anatomy it is a half-free intra-articular osteocartilaginous tissue, which can fully match a fossa observed at the femoral head. Histopathological examination found that the tissue was composed of collagenous fiber and cartilage-like tissue. Interestingly, we found the expression of type I collagen according to immunohistochemical analysis, which indicated that the cartilage-like tissue was formed due to laceration of the articular cartilage. This kind of disorder should be included as one of the pathologies of DDH. The most possible origin of this tissue is the femoral head which we speculate may have been fractured before. Keywords: Half-free intra-articular osteocartilaginous tissue, Developmental dysplasia of the hip, Pathology

Electrohydrodynamic jet 3D printing is an emerging and promising technology of microand nano-scale additive manufacturing with a low cost and high resolution, as well as a wide range of printed materials. However, due to the high printing speed and small standoff height between the nozzle and the substrate, it is especially difficult to directly observe and measure the printed patterns. Furthermore, there are many process parameters that affect the printing accuracy and quality, among which each parameter is coupling and interacting. This paper proposed a method of controlling the accuracy and quality of printed patterns based on the regulation of the shape and size of the Taylor cone by varying the process parameters. A theoretical model was then derived and established that describes the relationship between the line width printed with process parameters, printed material, and used substrate. Through the systematic experimental study, the influences and rules of the printing process parameters on the Taylor cone and printed patterns were revealed; Furthermore, the ideal jet printing window for the same nozzle was optimized. Finally, the feasibility and validity of the experimental results were demonstrated by the typical engineering cases, and a pattern of minimum line width of 3 μm was achieved with the nozzle diameter of 60 μm. The proposed method and experimental results provide a basis for further improving the accuracy, quality, and stability for electrohydrodynamic jet 3D printing, and the method offers a feasible solution for simplification and easy operation of actual 3D printing.

Timed event graphs are a subclass of Petri nets that are commonly applied for modeling and controlling manufacturing systems. In this paper, we investigate the problem of improving the performance of machines (servers) in timed event graphs in order to maximize the firing rate of a system. We show that the logic constraints on the cost of machines and the operation time of machines (firing delay of transitions) can be transformed into linear algebraic constraints. Furthermore, we formulate a mixed integer linear programming problem to maximize the firing rate of the net under a given budget for improving the performance of servers (decreasing the firing delay of transitions) that can provide an optimal solution. Finally, application to an assembly line is presented to show the effectiveness of the developed methodology.

We evaluated the prognosis of the new grade groups and American Joint Committee on Cancer (AJCC) stage groups in men with prostate cancer (PCa) who were treated conservatively. A total of 13 798 eligible men were chosen from the Surveillance Epidemiology and End Results database. The new grade and AJCC stage groups were investigated on prostate biopsy specimens. Kaplan–Meier survival analysis and multivariable hazards models were applied to estimate the association of new grade and stage groups with overall survival (OS) and PCa-specific survival (CSS). Mean follow-up was 42.65 months (95% confidence interval: 42.47–42.84) in the entire cohort. The 3-year OS and CSS rates stepped down for grade groups 1–5 and AJCC stage groups I–IVB, respectively. After adjusting for clinical and pathological characteristics, all grade groups and AJCC stage groups were associated with higher all-cause and PCa-specific mortality compared to the reference group (all P ≤ 0.003). In conclusion, we evaluated the oncological outcome of the new grade and AJCC stage groups on biopsy specimens of conservatively treated PCa. These two novel clinically relevant classifications can assist physicians to determine different therapeutic strategies for PCa patients.