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MicroRNAs (miRNAs) are important molecules that mediate virus-host interactions, mainly by regulating gene expression via gene silencing. Here, we demonstrated that HIV-1 infection upregulated miR-210-5p in HIV-1-inoculated cell lines and in the serum of HIV-1-infected individuals. Luciferase reporter assays and western blotting confirmed that a target protein of miR-210-5p, TGIF2, is regulated by HIV-1 infection. Furthermore, HIV-1 Vpr protein induced miR-210-5p expression. The use of a miR-210-5p inhibitor and TGIF2 overexpression showed that Vpr upregulated miR-210-5p and thereby downregulated TGIF2, which might be one of the mechanisms used by Vpr to induce G2 arrest. Moreover, we identified a transcription factor, NF-κB p50, which upregulated miR-210-5p in response to Vpr protein. In conclusion, we identified a mechanism whereby miR-210-5p, which is induced upon HIV-1 infection, targets TGIF2. This pathway was initiated by Vpr protein activating NF-κB p50, which promoted G2 arrest. These alterations orchestrated by miRNA provide new evidence on how HIV-1 interacts with its host during infection and increase our understanding of the mechanism by which Vpr regulates the cell cycle.

The construction method of tunnel has a critical impact on the stress and strain field during excavation. This study simulated the construction of Qichongcun tunnel by applying a different excavation method, including double-sided method, single-sided method, and three-step dynamic balance excavation method. The distribution and variation of the stress, vertical displacement, horizontal displacement of surrounding rocks, and stress of initial and secondary lining were studied. The results showed that large displacement of surrounding rocks would be induced during the construction in three-step method, but the stress of the second lining was small after completion of the construction. The displacement and stress of the three-step dynamic balance excavation method were larger than those of the other two methods, but it still met the requirements of safety.

Nef is an accessory protein encoded by human immunodeficiency virus type-1 (HIV-1) and plays important roles in regulating HIV-1 infection and viral replication. Interestingly, HIV-1 Nef can promote degradation of numerous host proteins to disrupt cellular antiviral immune response. However, how HIV-1 Nef is degraded by host factors remains largely unexplored. Here, we identified c-Cbl as a host ubiquitin E3 ligase of HIV-1 Nef. We found that c-Cbl interacts with Nef and reduces protein levels of HIV-1 Nef. Further studies demonstrated that c-Cbl promoted Lys48-linked polyubiquitination of HIV-1 Nef, thus attenuating protein stability of HIV-1 Nef. Importantly, cellular c-Cbl ubiquitinated and degraded Nef proteins produced by HIV-1 NL4-3 virions, and ultimately attenuated HIV-1 virulence for infection of THP1 cells. This study reveals a ubiquitination and proteasome-dependent degradation mechanism of HIV-1 Nef protein, and could provide potential strategies for fighting against HIV-1.

Mutations in the polycystin proteins, PC-1 and PC-2, result in autosomal dominant polycystic kidney disease (ADPKD) and ultimately renal failure. PC-1 and PC-2 enrich on primary cilia, where they are thought to form a heteromeric ion channel complex. However, a functional understanding of the putative PC-1/PC-2 polycystin complex is lacking due to technical hurdles in reliably measuring its activity. Here we successfully reconstitute the PC-1/PC-2 complex in the plasma membrane of mammalian cells and show that it functions as an outwardly rectifying channel. Using both reconstituted and ciliary polycystin channels, we further show that a soluble fragment generated from the N-terminal extracellular domain of PC-1 functions as an intrinsic agonist that is necessary and sufficient for channel activation. We thus propose that autoproteolytic cleavage of the N-terminus of PC-1, a hotspot for ADPKD mutations, produces a soluble ligand in vivo. These findings establish a mechanistic framework for understanding the role of PC-1/PC-2 heteromers in ADPKD and suggest new therapeutic strategies that would expand upon the limited symptomatic treatments currently available for this progressive, terminal disease.

The ambient vibration in manufacturing and assembly plants caused by nearby large equipment or heavy vehicles can produce dynamic machining error and even generate chatter in machining systems such as robotic drilling systems. In this paper, we present an active control method with a magnetorheological damper (MRD) for reducing ambient vibration in a robotic machining system, with the advantages of wider frequency bandwidth and robustness. A sliding mode control (SMC) algorithm is proposed as well. The control performance of the SMC under different excitations is simulated by Simulink and compared with that of the PID control algorithm; the result shows that the SMC is superior to the PID control and passive vibration control. An MRD is designed based on the control force of the active vibration control in the time domain in order to provide the required damping force. The results of co-simulation using ADAMS and Simulink verify that the ability of the SMC to control vibration performance is significantly improved compared with that of the passive vibration control.

As fossil fuels continue to be extracted and used, issues such as environmental pollution and energy scarcity are surfacing. For the transportation industry, the best way to achieve the goal of “carbon neutrality” is to research efficient power systems and develop new alternative fuels. As the world’s largest product of chemicals, ammonia is a new renewable fuel with good combustion energy. It can be used as an alternative fuel to reduce carbon emissions because of its proven production process, low production and transportation costs, safe storage, the absence of carbon-containing compounds in its emissions, and its future recyclability. This paper firstly introduces the characteristics of ammonia fuel engine and its problems; then it summarizes the effects of various ammonia-blended fuels on the combustion and emission characteristics of the engine from the combustion problem of ammonia-blended engine; then the fuel storage of ammonia-blended hydrogen is discussed, the feasibility of hydrogen production instead of hydrogen storage is introduced.

Population aging is occurring rapidly worldwide, challenging the global economy and healthcare services. Brain aging is a significant contributor to various age-related neurological and neuropsychological disorders, including Alzheimer’s disease and Parkinson’s disease. Several extrinsic factors, such as exposure to ionizing radiation, can accelerate senescence. Multiple human and animal studies have reported that exposure to ionizing radiation can have varied effects on organ aging and lead to the prolongation or shortening of life span depending on the radiation dose or dose rate. This paper reviews the effects of radiation on the aging of different types of brain cells, including neurons, microglia, astrocytes, and cerebral endothelial cells. Further, the relevant molecular mechanisms are discussed. Overall, this review highlights how radiation-induced senescence in different cell types may lead to brain aging, which could result in the development of various neurological and neuropsychological disorders. Therefore, treatment targeting radiation-induced oxidative stress and neuroinflammation may prevent radiation-induced brain aging and the neurological and neuropsychological disorders it may cause.

Abstract RNA helicase DDX21 plays vital roles in ribosomal RNA biogenesis, transcription, and the regulation of host innate immunity during virus infection. How DDX21 recognizes and unwinds RNA and how DDX21 interacts with virus remain poorly understood. Here, crystal structures of human DDX21 determined in three distinct states are reported, including the apo‐state, the AMPPNP plus single‐stranded RNA (ssRNA) bound pre‐hydrolysis state, and the ADP‐bound post‐hydrolysis state, revealing an open to closed conformational change upon RNA binding and unwinding. The core of the RNA unwinding machinery of DDX21 includes one wedge helix, one sensor motif V and the DEVD box, which links the binding pockets of ATP and ssRNA. The mutant D339H/E340G dramatically increases RNA binding activity. Moreover, Hill coefficient analysis reveals that DDX21 unwinds double‐stranded RNA (dsRNA) in a cooperative manner. Besides, the nonstructural (NS1) protein of influenza A inhibits the ATPase and unwinding activity of DDX21 via small RNAs, which cooperatively assemble with DDX21 and NS1. The structures illustrate the dynamic process of ATP hydrolysis and RNA unwinding for RNA helicases, and the RNA modulated interaction between NS1 and DDX21 generates a fresh perspective toward the virus–host interface. It would benefit in developing therapeutics to combat the influenza virus infection.

With widespread applications of artificial intelligence (AI), the capabilities of the perception, understanding, decision-making, and control for autonomous systems have improved significantly in recent years. When autonomous systems consider the performance of accuracy and transferability, several AI methods, such as adversarial learning, reinforcement learning (RL), and meta-learning, show their powerful performance. Here, we review the learning-based approaches in autonomous systems from the perspectives of accuracy and transferability. Accuracy means that a well-trained model shows good results during the testing phase, in which the testing set shares a same task or a data distribution with the training set. Transferability means that when a well-trained model is transferred to other testing domains, the accuracy is still good. Firstly, we introduce some basic concepts of transfer learning and then present some preliminaries of adversarial learning, RL, and meta-learning. Secondly, we focus on reviewing the accuracy or transferability or both of these approaches to show the advantages of adversarial learning, such as generative adversarial networks, in typical computer vision tasks in autonomous systems, including image style transfer, image super-resolution, image deblurring/dehazing/rain removal, semantic segmentation, depth estimation, pedestrian detection, and person re-identification. We furthermore review the performance of RL and meta-learning from the aspects of accuracy or transferability or both of them in autonomous systems, involving pedestrian tracking, robot navigation, and robotic manipulation. Finally, we discuss several challenges and future topics for the use of adversarial learning, RL, and meta-learning in autonomous systems. The Bigger Picture: Accuracy and transferability are critical to the perception and decision-making tasks of autonomous systems. The focus of several learning-based perception and decision-making methods has gradually evolved from accuracy to transferability. This survey summarizes the perception and decision-making tasks of autonomous systems from the perspectives of accuracy and transferability. We introduce transfer learning and some preliminaries of adversarial learning, reinforcement learning, and meta-learning. Then, we review several perception and decision tasks of autonomous systems from the perspectives of accuracy or transferability or both. Last but not least, we discuss several challenges and future works for using adversarial learning, reinforcement learning, and meta-learning in autonomous systems.

Inflammatory bowel disease (IBD) is a chronic disease that is commonly accompanied by increased inflammatory responses and elevated reactive oxygen species (ROS) of the gastrointestinal tract. Here, we found that MAPK-activated protein kinase 2 (MK2) modulates ROS production and is required for dextran sulfate sodium (DSS)-induced IBD in the mouse model. Genetic ablation of MK2 in the myeloid lineage cells (MK2Lyz2−KO) protected against DSS-induced colitis injury. In response to DSS challenge, compared to MK2lyz2−WT mice, MK2Lyz2−KO mice exhibited less damage of epithelial and goblet cells, decreased generation of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and ROS, as well as reduced Ki67-positive cells and concentrations of myeloperoxidase (MPO) in the intestinal epithelium. Furthermore, upon treatment with formylated peptide N-formyl-methionyl-leucyl-phenylalanine (fMLF), the generation of ROS was attenuated in MK2-deficient neutrophils, in which the phosphorylation of Akt and p38 MAPK was also reduced. Collectively, these findings indicated that MK2 is required for neutrophil-derived ROS production and IBD, and MK2 and ROS are promising therapeutic targets for IBD.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and lethal interstitial lung disease characterized by consistent pulmonary inflammation. Although protein kinase C delta (PKCδ) is involved in broad scope cellular response, the role of PKCδ in IPF is complicated and has not been fully defined yet. Here, we reported that PKCδ deficiency (PKCδ–/–) aggravated bleomycin (BLM)-induced pulmonary fibrosis and inflammation. Upon challenge with BLM, the pulmonary capillary permeability, immune cell infiltration, inflammatory cytokine production, and collagen deposition were enhanced in PKCδ–/– mice compared to that in PKCδ+/+ mice. In response to poly(I:C) stimulation, PKCδ deficient macrophages displayed an increased production of IL-1β, IL-6, TNF-α, and IL-33, which were associated with an enhanced NF-κB activation. Furthermore, we found that PKCδ could directly bind to and phosphorylate A20, an inhibitory protein of NF-κB signal. These results suggested that PKCδ may inhibit the NF-κB signaling pathway via enhancing the stability and activity of A20, which in turn attenuates pulmonary fibrosis, suggesting that PKCδ is a promising target for treating pulmonary fibrosis.

CREB-binding protein (CBP) participates in numerous transcription events. However, cell-intrinsic inhibitors of CBP are poorly defined. Here, we found that cellular USP12 interacts with the HAT domain of CBP and inhibits CBP's acetyltransferase activity. Interestingly, USP12 positively regulates interferon (IFN) antiviral signaling independently of its deubiquitinase activity. Furthermore, we found that in IFN signaling USP12 translocates from the cytoplasm to the nucleus. The decrease in cytoplasmic USP12 facilitates CBP-induced acetylation and activation of IFN signaling proteins in the cytoplasm. Moreover, USP12 accumulation in the nucleus blocks CBP-induced acetylation of phosphorylated STAT1 (p-STAT1) and therefore inhibits the dephosphorylation effects of TCPTP on p-STAT1, which finally maintains nuclear p-STAT1 levels and IFN antiviral efficacy. USP12 nuclear translocation extends our understanding of the regulation of the strength of IFN antiviral signaling. Our study uncovers a cell-intrinsic regulation of CBP acetyltransferase activity and may provide potential strategies for IFN-based antiviral therapy.

Conventional optimization methods are not efficient enough to solve many of the naturally complicated optimization problems. Thus, inspired by nature, metaheuristic algorithms can be utilized as a new kind of problem solvers in solution to these types of optimization problems. In this paper, an optimization algorithm is proposed which is capable of finding the expected quality of different locations and also tuning its exploration-exploitation dilemma to the location of an individual. A novel particle swarm optimization algorithm is presented which implements the conditioning learning behavior so that the particles are led to perform a natural conditioning behavior on an unconditioned motive. In the problem space, particles are classified into several categories so that if a particle lies within a low diversity category, it would have a tendency to move towards its best personal experience. But, if the particle’s category is with high diversity, it would have the tendency to move towards the global optimum of that category. The idea of the birds’ sensitivity to its flying space is also utilized to increase the particles’ speed in undesired spaces in order to leave those spaces as soon as possible. However, in desirable spaces, the particles’ velocity is reduced to provide a situation in which the particles have more time to explore their environment. In the proposed algorithm, the birds’ instinctive behavior is implemented to construct an initial population randomly or chaotically. Experiments provided to compare the proposed algorithm with the state-of-the-art methods show that our optimization algorithm is one of the most efficient and appropriate ones to solve the static optimization problems.

Abstract Adipocyte enhancer binding protein 1 (AEBP1) is a transcriptional repressor that plays a critical role in regulating adipogenesis. Recent studies have indicated that AEBP1 might function as a candidate oncogene and is overexpressed in several human malignancies. However, the role of AEBP1 in gastric cancer (GC) remains largely unknown. This study aimed to investigate the expression pattern, prognostic significance and biological function of AEBP1 in human gastric cancer and to explore the underlying mechanism. We found that both the mRNA and protein levels of AEBP1 were significantly increased in human GC tissues. Elevated AEBP1 expression was significantly correlated with poor overall survival in patients with both early-stage (Tumor, Node, Metastases (TNM) TNM I and II) and late-stage (TNM III and IV) GC. Silencing AEBP1 markedly suppressed the proliferation, migration, invasion, metastasis and epithelial-mesenchymal transition of GC cells. Moreover, we demonstrated that knockdown of AEBP1 in GC cells led to inhibition of the NF-κB pathway by hampering the degradation of IκBα. Thus, AEBP1 might be served as a promising prognostic indicator and a potential therapeutic target in human GC.

Abstract Idiopathic pulmonary fibrosis is a progressive interstitial pneumonia characterised by fibroblast accumulation, collagen deposition and extracellular matrix (ECM) remodelling. It was reported that Akt1 mediated idiopathic pulmonary fibrosis progression through regulating the apoptosis of alveolar macrophage, while its effect on macrophage-produced cytokines remains largely unknown. In the present study, we first examined the phosphorylation of Akt1 in lung sections from idiopathic pulmonary fibrosis patients by immunohistochemistry before applying a bleomycin-induced idiopathic pulmonary fibrosis model using Akt1 −/− mice and Akt1 +/+ littermates. The results showed that Akt1 was remarkably up-regulated in idiopathic pulmonary fibrosis patients, while in vivo studies revealed that Akt1-deficient mice had well-preserved alveolar structure and fewer collagens, secreted fewer matrix components, including alpha smooth-muscle actin and fibronectin and survived significantly longer than Akt1 +/+ littermates. Additionally, the pro-fibrogenic cytokine IL-13 was down-regulated at least twofold in Akt1 −/− mice compared to the Akt1 +/+ group on d 3 and 7 after bleomycin treatment. Furthermore, it was found that Akt1 –/– macrophages displayed down-regulation of IL-13 compared to Akt1 +/+ macrophages in which Akt1 was phosphorylated in response to IL-33 stimulation. These findings indicate that Akt1 modulates pulmonary fibrosis through inducing IL-13 production by macrophages, suggesting that targeting Akt1 may simultaneously block the fibrogenic processes of idiopathic pulmonary fibrosis.

Abstract Background Gastric cancer occupies the fourth highest morbidity rate of cancers worldwide. Clinical therapies of gastric cancer remain limited because of uncertainty of mechanisms and shortness of effective medicine. Thus, new drug candidates for gastric cancer treatment is urgently needed. Results In this study, CMPD1 as a wildly used MK2 phosphorylation inhibitor was employed to find its impact on gastric cancer cell proliferation, apoptosis and cell cycle using colony formation assay and flow cytometry analysis. Along with its anti-proliferation effect on gastric cancer cell line MKN-45 and SGC7901, CMPD1 also induced massive apoptosis and significant G2/M phase arrest in a time-dependent and dose-dependent manner in MKN-45 cells respectively. Furthermore, Western blot confirmed that the expression of anti-apoptotic proteins Bcl-2 was decreased while BAX, cytochrome c release and cleaved PARP were increased. In addition, oncogene c-Myc was downregulated in response to CMPD1 treatment. Conclusions Our results demonstrated that CMPD1 has anti-tumor effect on human gastric cancer cell line MKN-45 possibly via downregulating oncogene c-Myc expression and CMPD1 could be applied as a potential candidate for treating gastric malignancy. To the best of our knowledge, it is the first report of anti-tumor effect of CMPD-1 on human gastric cancer cells.

There are still many unsolved mysteries in the thermal decomposition process of urea. This paper studied the thermal decomposition process of urea at constant temperatures by the thermal gravimetric–mass spectrometry analysis method. The results show that there are three obvious stages of mass loss during the thermal decomposition process of urea, which is closely related to the temperature. When the temperature was below 160 °C, urea decomposition almost did not occur, and molten urea evaporated slowly. When the temperature was between 180 and 200 °C, the content of biuret, one of the by-products in the thermal decomposition of urea, reached a maximum. When the temperature was higher than 200 °C, the first stage of mass loss was completed quickly, and urea and biuret rapidly broke down. When the temperature was about 240 °C, there were rarely urea and biuret in residual substance; however, the content of cyanuric acid was still rising. When the temperature was higher than 280°C, there was a second stage of mass loss. In the second stage of mass loss, when the temperature was higher than 330 °C, mass decreased rapidly, which was mainly due to the decomposition of cyanuric acid. When the temperature was higher than 380 °C, the third stage of mass loss occurred. However, when the temperature was higher than 400 °C, and after continuous heating was applied for a sufficiently long time, the residual mass was reduced to almost zero eventually.

Vibrations in the aircraft assembly building will affect the precision of the robotic drilling system. A variable stiffness and damping semiactive vibration control mechanism with quasi-zero stiffness characteristics is developed. The quasi-zero stiffness of the mechanism is realized by the parallel connection of four vertically arranged bearing springs and two symmetrical horizontally arranged negative stiffness elements. Firstly, the quasi-zero stiffness parameters of the mechanism at the static equilibrium position are obtained through analysis. Secondly, the harmonic balance method is used to deal with the differential equations of motion. The effects of every parameter on the displacement transmissibility are analyzed, and the variable parameter control strategies are proposed. Finally, the system responses of the passive and semiactive vibration isolation mechanisms to the segmental variable frequency excitations are compared through virtual prototype experiments. The results show that the frequency range of vibration isolation is widened, and the stability of the vibration control system is effectively improved without resonance through the semiactive vibration control method. It is of innovative significance for ambient vibration control in robotic drilling systems.

As a complex field-circuit coupling system comprised of electric, magnetic and thermal machines, the permanent magnet synchronous motor of the electric vehicle has various operating conditions and complicated condition environment. There are various forms of failure, and the signs of failure are crossed or overlapped. Randomness, secondary, concurrency and communication characteristics make it difficult to diagnose faults. Meanwhile, the common intelligent diagnosis methods have low accuracy, poor generalization ability and difficulty in processing high-dimensional data. This paper proposes a method of fault feature extraction for motor based on the principle of stacked denoising autoencoder (SDAE) combined with the support vector machine (SVM) classifier. First, the motor signals collected from the experiment were processed, and the input data were randomly damaged by adding noise. Furthermore, according to the experimental results, the network structure of stacked denoising autoencoder was constructed, the optimal learning rate, noise reduction coefficient and the other network parameters were set. Finally, the trained network was used to verify the test samples. Compared with the traditional fault extraction method and single autoencoder method, this method has the advantages of better accuracy, strong generalization ability and easy-to-deal-with high-dimensional data features.

In order to enhance the capability of resistant to protein adsorption of the copolymer membrane of polyacryloylmorpholine-graft-acryloylmorpholine(PVDF-g-PACMO), a crosslinking agent of ethylene glycoldimethacrylate(EGDMA) was added to prepare the copolymer.The copolymers with different proportions of the crosslinking agent were cast into flat membranes via a liquid-liquid phase separation technique, and then the influence of EGDMA contained in the membranes on its capability of resistant to protein adsorption was investigated. FT-IR results indicate the PVDF-g-PACMO copolymers with EGDMA are synthesized successfully. A series of tests, including XPS, SEM, the contact angle, the static protein adsorption and permeation experiments, show that PACMO is much easier to segregate to the surface with the increase of the crosslinking agent content in the system, the number of membrane pores increases, meantime, the hydrophilicity and water flux of the copolymer membranes are improved. Moreover, the adsorption amount of protein, total pollution index and irreversible pollution index decrease, and reversible pollution index increases. All results indicate the crosslinking agent of EGDMA can enhance the capability of resistant to protein adsorption of PVDF-g-PACMO membranes.

Abstract Formyl peptide receptors (FPRs) are G protein-coupled chemoattractant receptors expressed mainly in phagocytic leukocytes. High expression of FPRs has also been detected in several cancers but the functions of FPR1 in tumor invasion and metastasis is poorly understood. In this study, we investigated the expression of FPRs in primary human colorectal cancer (CRC) and analyzed the association of FPRs expression with clinicopathological parameters. The levels of FPRs mRNA, especially those of FPR1, were significantly higher in colorectal tumors than in distant normal tissues and adjacent non-tumor tissues. FPR1 mRNA expression was also associated with tumor serosal infiltration. FPR1 protein expression was both in the colorectal epitheliums and tumor infiltrating neutrophils/macrophages. Furthermore, the functions of FPR1 in tumor invasion and tissue repair were investigated using the CRC cell lines SW480 and HT29. Higher cell surface expression of FPR1 is associated with significantly increased migration in SW480 cells compared with HT29 cells that have less FPR1 membrane expression. Finally, genetic deletion of fpr1 increased the survival rate of the resulting knockout mice compared with wild type littermates in a mouse model of colitis-associated colorectal cancer. Our data demonstrate that FPR1 may play an important role in tumor cell invasion in CRC patients.

Abstract Background Neoadjuvant chemotherapy is a key component of breast cancer treatment regimens and pathologic complete response to this therapy varies among patients. This is presumably due to differences in the molecular mechanisms that underlie each tumor’s disease pathology. Developing genomic clinical assays that accurately categorize responders from non-responders can provide patients with the most effective therapy for their individual disease. Methods We applied our previously developed E2F4 genomic signature to predict neoadjuvant chemotherapy response in breast cancer. E2F4 individual regulatory activity scores were calculated for 1129 patient samples across 5 independent breast cancer neoadjuvant chemotherapy datasets. Accuracy of the E2F4 signature in predicting neoadjuvant chemotherapy response was compared to that of the Oncotype DX and MammaPrint predictive signatures. Results In all datasets, E2F4 activity level was an accurate predictor of neoadjuvant chemotherapy response, with high E2F4 scores predictive of achieving pathologic complete response and low scores predictive of residual disease. These results remained significant even after stratifying patients by estrogen receptor (ER) status, tumor stage, and breast cancer molecular subtypes. Compared to the Oncotype DX and MammaPrint signatures, our E2F4 signature achieved similar performance in predicting neoadjuvant chemotherapy response, though all signatures performed better in ER+ tumors compared to ER- ones. The accuracy of our signature was reproducible across datasets and was maintained when refined from a 199-gene signature down to a clinic-friendly 33-gene panel. Conclusion Overall, we show that our E2F4 signature is accurate in predicting patient response to neoadjuvant chemotherapy. As this signature is more refined and comparable in performance to other clinically available gene expression assays in the prediction of neoadjuvant chemotherapy response, it should be considered when evaluating potential treatment options.

Abstract Background Esophageal squamous cell carcinoma (ESCC) is highly malignant with highly invasive and metastatic capabilities and poor prognosis. It is believed that the ESCC cancer stem-like cells (ECSLCs) are critical for tumorigenicity, invasion and metastasis of ESCC. However, the properties of ECSLCs vary with different markers used in isolation, so that new and more effective markers of ECSLCs need to be identified. This study aimed to estimate the potentiality of Cripto-1 (CR-1) as an ECSLC surface marker and investigate the clinical significance of CR-1 expression in ESCC. Methods ESCC cells with CR-1 high or CR-1low were obtained by flow cytometry then their self-renewal capability and tumorigenicity were compared by colony and limiting dilution sphere formation analysis in vitro and xenograft in nude mice in vivo, respectively. Knockdown of CR-1 expression in ESCC cells was conducted with short hairpin RNA. Cell migration and invasion were examined by scratch test and matrigel transwell assay, respectively. Metastatic capability of ESCC cells was assayed by a mouse tail vein metastasis model. The levels of CR-1 expression in cancerous and paired adjacent normal tissues were assessed by IHC and qRT-RCR. Results CR-1high subpopulation of ESCC cells isolated by FACS expressed high level of genes related to stemness and epithelial-mesenchymal transition (EMT), and possessed high capacities of self-renewal, tumorigenesis, invasion and metastasis. Suppression of CR-1 expression significantly reduced the expression of stemness- and EMT-related genes and the capabilities of self-renewal in vitro, tumorigenicity and metastasis in vivo in ESCC cells. In the clinical ESCC specimens, the expression levels of CR-1 in cancerous tissues were positively correlated to TNM stage, invasive depth, and lymph node metastasis. Cox regression analysis indicated that CR-1 was an independent indicator of prognosis. The expression of CR-1 was found overlapping with aldehyde dehydrogenase 1A1 (ALDH1A1), an intracellular marker for ESCLCs, in ESCC cell lines and specimens. Conclusions CR-1 is a functional and cell surface ECSLC marker, and an independent prognostic indicator as well as a potential therapeutic target for ESCC.

Given the significant requirements for transforming and promoting the process industry, we present the major limitations of current petrochemical enterprises, including limitations in decision-making, production operation, efficiency and security, information integration, and so forth. To promote a vision of the process industry with efficient, green, and smart production, modern information technology should be utilized throughout the entire optimization process for production, management, and marketing. To focus on smart equipment in manufacturing processes, as well as on the adaptive intelligent optimization of the manufacturing process, operating mode, and supply chain management, we put forward several key scientific problems in engineering in a demand-driven and application-oriented manner, namely: ① intelligent sensing and integration of all process information, including production and management information; ② collaborative decision-making in the supply chain, industry chain, and value chain, driven by knowledge; ③ cooperative control and optimization of plant-wide production processes via human-cyber-physical interaction; and ④ life-cycle assessments for safety and environmental footprint monitoring, in addition to tracing analysis and risk control. In order to solve these limitations and core scientific problems, we further present fundamental theories and key technologies for smart and optimal manufacturing in the process industry. Although this paper discusses the process industry in China, the conclusions in this paper can be extended to the process industry around the world.

Abstract The handheld ultrasound demonstrates clinical and economic value in combating COVID-19 based on interviews with frontline ultrasound physician and cardiologist as well as a national expert in medical ultrasound.

Abstract Large-area ultrafine MnO2 nanowire arrays (NWA) directly grew on a carbon fiber (CF, used as a substrate) by a simple electrochemical method, forming three-dimensional (3D) hierarchical heterostructures of a CF@MnO2 NWA composite. As an electrode for supercapacitors, the CF@MnO2 NWA composite exhibits excellent electrochemical performances including high specific capacitance (321.3 F g−1 at 1000 mA g−1) and good rate capability. Further, the overall capacitance retention is ~99.7 % capacitance after 3000 cycles. These outstanding electrochemical performances attribute to a large number of transport channels for the penetration of electrolyte and the transportation of ions and electrons of electrodes. The as-prepared CF@MnO2 NWA composite may be a promising electrode material for high-performance supercapacitors.

Introduction In contrast to orthotopic thyroid carcinoma, primary accessory thyroid carcinoma is very rare. We herein report a case involving primary accessory thyroid carcinoma in a patient with normal ultrasonography of the orthotopic thyroid and negative 99m TcO 4 − single-photon emission computed tomography (SPECT) scintigraphy. Case presentation: A computed tomography (CT) scan showed soft tissue nodules at the left anterior edge of the thyroid cartilage. To determine whether the mass was accessory thyroid tissue, 99m TcO 4 − SPECT/CT was performed, and the findings were negative. However, pathological examination after resection showed that mass was a primary accessory thyroid papillary carcinoma. The 1-year follow-up ultrasound showed no lesion at the orthotropic thyroid and neck incision sites. Conclusions This case suggests that negative 99m TcO 4 − SPECT/CT imaging may not completely exclude the possibility of thyroid carcinoma. A punch biopsy or postoperative pathological examination is necessary for the diagnosis.

ABSTRACT Endogenous retroviruses (ERVs) are transposable elements that cause host genome instability and usually play deleterious roles in disease such as tumorigenesis. Recent advances also suggest that this “enemy within” may encode a viral mimic to induce antiviral immune responses through viral sensors. Here, through whole-genome transcriptome analysis with RNA sequencing (RNA-Seq), we discovered that a full-length ERV-derived long noncoding RNA (lncRNA), designated lnc-EPAV (ERV-derived lncRNA positively regulates antiviral responses), was a positive regulator of NF-κB signaling. lnc-EPAV expression was rapidly upregulated by viral RNA mimics or RNA viruses to facilitate the expression of RELA, an NF-κB subunit that plays a crucial role in antiviral responses. Transcriptome analysis of lnc-EPAV-silenced macrophages showed that lnc-EPAV was critical for RELA target gene expression and innate immune responses. Consistently, lnc-EPAV-deficient mice exhibited reduced expression of type I interferons (IFNs) and, consequently, increased viral loads and mortality following lethal RNA virus infection. Mechanistically, lnc-EPAV promoted expression of RELA by competitively binding to and displacing SFPQ, a transcriptional repressor of Rela. Altogether, our work demonstrates an alternative mechanism by which ERVs regulate antiviral immune responses. IMPORTANCE Endogenous retroviruses are transposable genetic elements comprising 8% to 10% of the human and mouse genomes. Although most ERVs have been inactivated due to deleterious mutations, some are still transcribed. However, the biological functions of transcribed ERVs are largely unknown. Here, we identified a full-length ERV-derived lncRNA, designated lnc-EPAV, as a positive regulator of host innate immune responses. We found that silencing lnc-EPAV impaired virus-induced cytokine production, resulting in increased viral replication in cells. The lnc-EPAV-deficient mice exhibited enhanced susceptibility to viral challenge. We also found that lnc-EPAV regulated expression of RELA, an NF-κB subunit that plays a critical role in antiviral responses. ERV-derived lncRNA coordinated with a transcription repressor, SFPQ, to control Rela transcription. Our report provides new insights into the previously unrecognized immune gene regulatory mechanism of ERV-derived lncRNAs.

Phononic metamaterials are capable of manipulating mechanical wave propagation in applications ranging from nanoscale heat transfer to noise and vibration mitigation. The design of phononic metamaterials to control low-frequency vibrations, such as those induced by ground transportation and low-amplitude seismic waves, however, remains a challenge. Here we propose a new design methodology to generate seismic metamaterials that can attenuate surface waves below 10 Hz. Our design concept evolves around the engineering of the multi-layered soil, the use of conventional construction materials, and operational construction constraints. The proposed seismic metamaterials are constructed by periodically varying concrete piles in the host multi-layered soil. We first validate the design concept and the numerical models by performing a lab-scale experiment on the low-amplitude surface wave propagation in a finite-size seismic metamaterial. To the best of the Authors' knowledge, this is one of the few attempts made to date to experimentally understand the vibration mitigation capability of seismic metamaterials. We then numerically demonstrate that the multi-layered seismic metamaterials can attenuate surface waves over a wide frequency range, with the incident wave energy being confined within the softest layer of the shallow layered seismic metamaterials. In addition to the localized wave energy distribution, deep layered seismic metamaterials exhibit broadband cut-off band gaps up to 7.2 Hz due to the strongly imposed constraint between piles and surrounding soil. Furthermore, these cut-off band gaps strongly depend on the constraint between the piles and the bottom layer of the soil and hence can be tuned by tailoring the foundation stiffness. We also evidence the possibility to create constant wave band gaps by introducing hollow concrete piles with pile volume fraction

Background: cKIT kinase overexpression and gain-of-function mutations are the critical pathogenesis of gastrointestinal stromal tumors (GISTs). Although the multiple kinase inhibitors such as imatinib, sunitinib, and regorafenib have been approved for GISTs, the acquisition of polyclonal secondary resistance mutations in KIT is still a limitation for GIST treatment. Here we explored the KIT inhibitory activity of axitinib in preclinical models and describe initial characterization of its activity in GIST patient-derived primary cells. Methods: The activities of axitinib against mutant KIT were evaluated using protein-based assay and a panel of engineered and GIST-derived cell lines. The binding modes of axitinib-KIT/KIT mutants were analyzed. Four primary cells derived from GIST patients were also used to assess the drug response of axitinib. Results: Axitinib exhibited potent activities against a variety of cKIT associated primary and secondary mutations. It displayed better activity against cKIT wild-type, cKIT V559D/A/G, and L576P primary gain-of-function mutations than imatinib, sunitinib, and regorafenib. In addition, it could inhibit imatinib resistant cKIT T670I and V654A mutants in vitro and in vivo GIST preclinical models. Conclusion: Our results provide the basis for extending the application of axitinib to GISTs patients who are unresponsive or intolerant to the current therapies.

In the carrier-based coverage repair problem, a single mobile robot replaces damaged sensors by picking up spare ones in the region of interest or carrying them from a base station in wireless sensor and robot networks. The objective is to find the shortest path of the robot. The problem is an extension of the traveling salesman problem (TSP). Thus, it is also called the one-commodity traveling salesman problem with selective pickup and delivery (1-TSP-SELPD). In order to solve this problem in a larger sensor distribution scenario more efficiently, we propose a two-stage approach in this paper. In the first stage, the mature and effective Lin-Kernighan-Helsgaun (LKH) algorithm is used to form a Hamiltonian cycle for all delivery nodes, which is regarded as a heuristic for the second stage. In the second stage, elliptical regions are set for selecting pickup nodes' and an edge-ordered list (candidate edge list, CEL) is constructed to provide major axes for the ellipses. The process of selecting pickup nodes and constructing the CEL is repeated until all the delivery nodes are visited. The final CEL stores a feasible solution. To update it, three operations-expansion, extension, and constriction-are applied to the CEL. The experimental results show that the proposed method reduces the computing time and achieves better results in higher-dimensional problems, which may facilitate the provision of solutions for more complicated sensor networks and can contribute to the development of effective and efficient algorithms for the one-commodity pickup-and-delivery traveling salesman problem (1-PDTSP).

It is difficult to develop accurate mathematical models to describe the range extender electric vehicles due to the non-linear and complex coupling of the monitoring signal sources resulted from the massive moving parts and complex architecture in range extender and the limited storage space of the diagnostic device. In this study, we proposed the smooth iterative online support tensor machine algorithm, which is combined with support higher-order tensor machine and online stochastic gradient descent method, and applied it to the fault diagnosis of the range indicator. Four methods with different algorithms, support vector machine, smooth iterative online support vector machine, linear support higher-order tensor machine, and smooth iterative online support tensor machine algorithms, were adopted to diagnose and classify the fault samples of the range indicator by comparing the diagnostic accuracy and model learning time. It is found that the fault diagnosis method based on the smooth iterative online tensor machine showed a higher accuracy, shorter learning time, and less storage space. Based on the experimental results, it is feasible to apply smooth iterative online support tensor machine model to the fault diagnosis of electric vehicle extenders.

Increased inflammatory responses and enhanced reactive oxygen species contribute to hepatic ischemia/reperfusion (I/R) injury, however the modulatory mechanisms haven't been completely unveiled. Here, we report that genetic deficiency of MAPK-activated protein kinase 2 (MK2) protected against hepatic I/R injury and decreased hepatic neutrophil accumulation in MK2−/− mice. Depletion of neutrophil attenuated hepatic I/R injury in wide type mice. In response to C5a stimulation, MK2−/− neutrophils generated less superoxide in which both NADPH oxidase activation and p47phox phosphorylation were decreased. Furthermore, Ser329 of p47phox was identified for enhancement of superoxide production. The Ser329 phosphorylation was reduced in MK2−/− neutrophils. To determine whether MK2 modulates hepatic I/R injury via activating neutrophils, we generated myeloid-specific MK2 deletion mice (MK2Lyz2−KO) and liver I/R injury was reduced in MK2Lyz2−KO mice. Our results indicate that MK2 augments hepatic I/R injury and induces ROS production with increased p47phox phosphorylation and MK2 is a potential drug target for treating hepatic I/R injury.

Patients receiving brain radiotherapy may suffer acute or chronic side effects. Ionizing radiation induces the production of intracellular reactive oxygen species and pro-inflammatory cytokines in the central nervous system, leading to brain damage. Complementary Chinese herbal medicine therapy may reduce radiotherapy-induced side effects. Flavonoids are a class of natural products which can be extracted from Chinese herbal medicine and have been shown to have neuroprotective and radioprotective properties. Flavonoids are effective antioxidants and can also inhibit regulatory enzymes or transcription factors important for controlling inflammatory mediators, affect oxidative stress through interaction with DNA and enhance genomic stability. In this paper, radiation-induced brain damage and the relevant molecular mechanism were summarized. The radio-neuro-protective effect of flavonoids, i.e., antioxidant, anti-inflammatory and maintaining genomic stability, were then reviewed. We concluded that flavonoids treatment may be a promising complementary therapy to prevent radiotherapy-induced brain pathophysiological changes and cognitive impairment.

A novel coagulation combined with UV/O3 process was employed to remove the effluent organic matter (EfOM) from a biotreated pharmaceutical wastewater for harmlessness. The removal behavior of EfOM by UV/O3 process was characterized by synchronous fluorescence spectroscopy (SFS) integrating two-dimensional correlation (2D-COS) and principal component analysis (PCA) technology. The highest dissolved organic carbon (DOC) and ratio of UV254 and DOC (SUVA) removal efficiency reached 55.8% and 68.7% by coagulation-UV/O3 process after 60 min oxidation, respectively. Five main components of pharmaceutical tail wastewater (PTW) were identified by SFS. Spectral analysis revealed that UV/O3 was selective for the removal of different fluorescent components, especially fulvic acid-like fluorescent (FLF) component and humus-like fluorescent (HLF) component. Synchronous fluorescence/UV-visible two-dimensional correlation spectra analysis showed that the degradation of organic matter occurred sequentially in the order of HLF, FLF, microbial humus-like fluorescence component (MHLF), tryptophan-like fluorescent component (TRLF), tyrosine-like fluorescent component (TYLF). The UV/O3 process removed 95.6% of HLF, 80.0% of FLF, 56.0% of TRLF, 50.8% of MHLF and 44.4% of TYLF. Therefore, the coagulation-UV/O3 process was proven to be an attractive way to reduce the environmental risks of PTW.

A pilot-scale experiment is carried out for treating mixed wastewater containing pharmaceutical wastewater (PW) and domestic wastewater (DW), by a process that is a combination of hydrolysis acidification-ozone-modified anaerobic–anoxic–aerobic-ozone (A2/O) (pre-ozone) or hydrolysis acidification-modified A2/O-ozone (post-ozone). The effects of different mixing ratios of PW and DW and pre-ozone treatment or post-ozone treatment on the removal of nitrogen and phosphorus and chemical oxygen demand (COD) are compared and studied. The optimal ratio of PW in mixing wastewater is 30%, which has the optimal COD removal efficiency and minimum biotoxicity to biological treatment. The pre-ozone treatment shows more advantages in removing nitrogen and phosphate but the post-ozone treatment shows more advantages in COD removal. Analysis of dissolved organic matter (DOM) demonstrates that post-ozone treatment has a more significant effect on the removal of fulvic acid and humic acid than the effect from the pre-ozone treatment, so the COD removal is better. Overall DOM degradation efficiency by post-ozone treatment is 55%, which is much higher than the pre-ozone treatment efficiency of 38%. Microbial community analysis reveals that the genus Thauera and the genus Parasegetibacter take great responsibility for the degradation of phenolics in this process. All the results show that the post-ozone treatment is more efficient for the mixed wastewater treatment in refractory organics removal.

This paper takes the second-stage Guxi Shanshui Residential District in Dang Tu County as an example to analyze the characteristics of it from the aspects of function, traffic, landscape, and house types. And we explore the planning and design of the modern residential district by this research, and hope to make useful contributions to the development and construction of the future residential district planning and design.

Polycystic kidney disease (PKD) is a ciliopathy resulting from defective localization of membrane proteins such as PC-1 to the primary cilium, resulting in renal cysts, and is associated with another cystic genetic disease called tuberous sclerosis complex (TSC). Here the authors use kidney-specific Tsc1 and Pkd1 mice to show that mTORC1 signalling inhibits PC-1 biogenesis as a potential mechanism of TSC/PKD contiguous gene syndrome.

Urea-Selective Catalytic Reduction (SCR) is widely used to reduce nitrogen oxide (NOx) emissions. This paper presents a comprehensive experimental research work on aftertreatment emissions of NOx and ammonia (NH3) slip for three aftertreatment concepts by introducing the SCR sizing strategy on a 6-cylinder mid-range non-exhaust gas recirculation (EGR) diesel engine to meet China non-road Stage IV regulation limits. It can be observed that the three concepts could meet the regulation limits for NOx emissions and NH3 slip by selecting the appropriate length. There is little effect on emission results during a non-road transient cycle (NRTC) when the aftertreatment inlet/outlet with insulation and without insulation and the emission results on both strategies could meet non-road China Stage IV regulation limits. It is recommended to select Concept 2 which could meet regulation requirements considering multiple factors in the SCR sizing strategy. Substrate impact and NH3/NOx molar ratio (ANR) impact are investigated based on Concept 2. The results show that by applying the SCR substrate aftertreatment with a cell density of 600 cpsi, NOx conversion capability is stronger than that with cell density 400 cpsi for the same SCR size. Current dosing strategy is capable and recommended ANR is 0.9–1.1 if considering dosing strategy optimization. The methodology in this study provides an effective guidance and reference for future aftertreatment SCR sizing strategies in real applications.