HOXC4 promotes proliferation of pancreatic cancer cells by increasing LDHA-mediated glycolysis.

Homeobox C4 (HOXC4) is a member of homeobox family and acts as a transcription factor in regulating morphological development. The current study aimed to determine its role in pancreatic cancer (PC). Bioinformatics analysis was employed to assess the expression and clinical significance of HOXC4 in PC, while the expression of HOXC4 was further confirmed in PC tissues through quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The impact of HOXC4 on PC cell proliferation was evaluated using various assays including Cell Counting Kit-8, colony formation, apoptosis detection, cell cycle analysis, and subcutaneous tumorigenesis. Extracellular acidification rate, glucose uptake, and lactate production measurements were detected to examine the impact of HOXC4 on glycolysis. The relationship between HOXC4 and lactate dehydrogenase A (LDHA) was investigated using CHIP assay, luciferase reporter assay, and western blot. Notably, there was a substantial increase in HOXC4 expression in PC, and patients with elevated HOXC4 levels exhibited shorter survival durations. HOXC4 knockdown resulted in significantly reduced proliferation and colony formation in PC cells, accompanied by increased apoptosis and G1 phase arrest. The overexpression of HOXC4 resulted in contrasting effects. In vivo, the proliferation of PC cells was diminished upon the knockdown of HOXC4. HOXC4 exhibited an increase in LDHA expression by binding to its promoter. The suppressive effects of HOXC4 knockdown on PC cells were counteracted upon the restoration of LDHA. In conclusion, HOXC4 promoted the proliferation of PC cells by increasing LDHA-mediated glycolysis. HOXC4 can act as a target for PC therapy.

Characterization of the substernal space with computed tomography imaging in patients with and without median sternotomy: Assessing a novel implant location for extravascular defibrillation lead placement.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) provide clinically significant therapy for the prevention of sudden cardiac death. This study aimed to characterize the substernal space using computed tomography (CT) in patients with and without prior midline sternotomy to investigate the feasibility of substernal ICD lead implantation in post-sternotomy patients. METHODS: High-quality electrocardiogram-gated CT images from 100 patients (71% male, average body mass index 23.5 ± 2.9) were retrospectively collected, including 50 patients with prior midline sternotomy (S-group) and 50 patients with no prior sternotomy (NS-group). Distances were measured from the retrosternal surface to the epicardial surface of the heart and segmented into four regions from the xiphoid tip and superiorly along the sternum. RESULTS: Results generally showed a measurable but narrower average sternum-to-heart distance in the prior sternotomy group compared to the non-sternotomy group in all four regions (p < .05). In the S-group, the sternum-to-heart distances across all regions ranged from 0 to 32.0 mm, while in the NS-group, the distances ranged from 0 to 39.9 mm. CONCLUSION: Small but measurable separations between the heart and sternum were observed in patients with prior sternotomy, particularly near the xiphoid region, indicating the potential viability of extravascular substernal ICD lead implantation in post-sternotomy patients.

Hsa_circ_0014784-induced YAP1 promoted the progression of pancreatic cancer by sponging miR-214-3p.

BACKGROUND: Pancreatic cancer (PC) is one of the most common gastrointestinal tumors globally. Former investigations discovered that circular RNAs (circRNAs) play an important role in PC development. circRNAs belong to a new class of endogenous noncoding RNAs, which have been found to mediate the progression of diverse types of tumors. Nevertheless, the roles of circRNAs and the underlying regulatory mechanisms in PC remain unknown. METHODS: In this study, our team employed next-generation sequencing (NGS) to examine the abnormal circRNA expression in PC tissues. The circRNA expression in PC cell lines and tissues was detected. Then, regulatory mechanism and targets were examined with bioinformatics analysis, luciferase reporting analysis, Transwell migration, 5-ethynyl-2'-deoxyuridine, and CCK-8 analysis. An in vivo experiment was employed to elucidate hsa_circ_0014784 roles in PC tumor growth and metastasis. RESULTS: The results showcased abnormal circRNA expression in PC tissues. Our lab also found that hsa_circ_0014784 expression incremented in PC tissues and cell lines, implying that hsa_circ_0014784 functioned in PC progression. hsa_circ_0014784 downregulation inhibited PC proliferation and invasion in vivo and in vitro. The bioinformatics and luciferase report data validated that both miR-214-3p and YAP1 were hsa_circ_0014784 binding partners. The overexpression of YAP1 reversed the migration, proliferation, and epithelial - mesenchymal transition (EMT) of PC cells and the angiogenic differentiation of HUVECs after miR-214-3p overexpression. CONCLUSION: Taken together, our study found that hsa_circ_0014784 downregulation decremented invasion, proliferation, EMT, and angiogenesis of PC by regulating miR-214-3p/YAP1 signaling.

Smart Cup for In-Situ 3D Measurement of Wall-Mounted Debris via 2D Sensing Grid in Production Pipelines.

The accumulation of separated out impurities from pipeline transported medium onto the pipe wall is a major cause of downtime maintenance of oil and gas production systems. To regularly scrub off wall-mounted debris and probe the severity, pipeline inspection gauges (PIG) are the state-of-the-art tools developed for the task, using the pressure differential across the device as the driving force, and tag-along sensing equipment for wall defects measurement. Currently, the PIG propulsion and sensing tasks are realized by separate compartments, limited to large diameter operations. In this work, a soft solution for medium to small diameter pipelines has been demonstrated. The smart cup with integrated sensing grid is proposed to achieve integrated wall-mounted debris dimensional measurement, without the need of additional sensors. To achieve the goal, this work starts from the mathematical modelling of the geometric problem, to new fabrication procedures, experimental setup, and finally finishes with validation results. Initial results have shown that using the proposed smart cup, the wall-mounted debris can be detected, with modelling error maxed at 5.1%, and deformation detection accuracy between 1.18% and 1.92% with respect to the outer diameter.

The application of the nnU-Net-based automatic segmentation model in assisting carotid artery stenosis and carotid atherosclerotic plaque evaluation.

Objective: No new U-net (nnU-Net) is a newly-developed deep learning neural network, whose advantages in medical image segmentation have been noticed recently. This study aimed to investigate the value of the nnU-Net-based model for computed tomography angiography (CTA) imaging in assisting the evaluation of carotid artery stenosis (CAS) and atherosclerotic plaque. Methods: This study retrospectively enrolled 93 CAS-suspected patients who underwent head and neck CTA examination, then randomly divided them into the training set (N = 70) and the validation set (N = 23) in a 3:1 ratio. The radiologist-marked images in the training set were used for the development of the nnU-Net model, which was subsequently tested in the validation set. Results: In the training set, the nnU-Net had already displayed a good performance for CAS diagnosis and atherosclerotic plaque segmentation. Then, its utility was further confirmed in the validation set: the Dice similarity coefficient value of the nnU-Net model in segmenting background, blood vessels, calcification plaques, and dark spots reached 0.975, 0.974 0.795, and 0.498, accordingly. Besides, the nnU-Net model displayed a good consistency with physicians in assessing CAS (Kappa = 0.893), stenosis degree (Kappa = 0.930), the number of calcification plaque (Kappa = 0.922), non-calcification (Kappa = 0.768) and mixed plaque (Kappa = 0.793), as well as the max thickness of calcification plaque (intraclass correlation coefficient = 0.972). Additionally, the evaluation time of the nnU-Net model was shortened compared with the physicians (27.3 ± 4.4 s vs. 296.8 ± 81.1 s, p < 0.001). Conclusion: The automatic segmentation model based on nnU-Net shows good accuracy, reliability, and efficiency in assisting CTA to evaluate CAS and carotid atherosclerotic plaques.

NAP1L5 targeting combined with MYH9 Inhibit HCC progression through PI3K/AKT/mTOR signaling pathway.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. Nucleosome assembly protein 1-like 5 (NAP1L5) is a protein-coding gene that encodes a protein similar to nucleosome assembly protein 1 (NAP1). It is a histone chaperone that plays an important role in gene transcription in organisms. However, the role of NAP1L5 in the pathogenesis of hepatocellular carcinoma remains to be elucidated. In this study, low expression of NAP1L5 was found in hepatocellular carcinoma, and the downregulation of NAP1L5 was related to shorter survival and disease-free survival. In addition, its expression is also related to the tumor size and recurrence of hepatocellular carcinoma. The overexpression and knockdown of NAP1L5 by plasmid and siRNA showed that NAP1L5 inhibited the proliferation, migration and invasion and induced apoptosis of hepatoma cells. In vivo experiments confirmed that NAP1L5 can inhibit the growth and metastasis of hepatocellular carcinoma cells. In the mechanistic study, we found that NAP1L5 affects the occurrence and development of hepatocellular carcinoma by regulating MYH9 to inhibit the PI3K/AKT/mTOR signaling pathway. As a functional tumor suppressor, NAP1L5 is expressed at low levels in HCC. NAP1L5 inhibits the PI3K/AKT/mTOR signaling pathway in hepatocellular carcinoma by regulating MYH9. It may be a new potential target for liver cancer treatment.

Dynamic Modeling and Experimental Validation of a Water Hydraulic Soft Manipulator Based on an Improved Newton-Euler Iterative Method.

Compared with rigid robots, soft robots have better adaptability to the environment because of their pliability. However, due to the lower structural stiffness of the soft manipulator, the posture of the manipulator is usually decided by the weight and the external load under operating conditions. Therefore, it is necessary to conduct dynamics modeling and movement analysis of the soft manipulator. In this paper, a fabric reinforced soft manipulator driven by a water hydraulic system is firstly proposed, and the dynamics of both the soft manipulator and hydraulic system are considered. Specifically, a dynamic model of the soft manipulator is established based on an improved Newton-Euler iterative method, which comprehensively considers the influence of inertial force, elastic force, damping force, as well as combined bending and torsion moments. The dynamics of the water hydraulic system consider the effects of cylinder inertia, friction, and water response. Finally, the accuracy of the proposed dynamic model is verified by comparing the simulation results with the experimental data about the steady and dynamic characteristics of the soft manipulator under various conditions. The results show that the maximum sectional error is about 0.0245 m and that the maximum cumulative error is 0.042 m, which validate the effectiveness of the proposed model.

Design and Performance Study for Electrothermally Deep-Sea Drive Microunits Using a Paraffin Phase Change Material.

Considering the further exploration of the ocean, the requirements for deep-sea operation equipment have increased. Many problems existing in the widely used deep-sea hydraulic system have become increasingly prominent. Compared with the traditional deep-sea hydraulic system, actuators using a paraffin phase change material (PCM) have incomparable advantages, including lightweight structure, low energy consumption, high adaptability to the deep sea, and good biocompatibility. Thus, a deep-sea drive microunit (DDM) based on paraffin PCM is proposed in this paper. The device adopts a flexible shell, adapting to the high-pressure environment of the deep-sea based on the principle of pressure compensation. The device realizes the output of displacement and force through the electrothermal drive, which can be used as actuator or power source of other underwater operation equipment. The microunit successfully completes the functional verification experiments in air, shallow water, and hydrostatic pressure of 110 MPa. In accordance with experimental results, a reasonable control curve is fitted, highlighting its potential application in deep-sea micro electro mechanical systems, especially in underwater soft robot.

miR-29b restrains cholangiocarcinoma progression by relieving DNMT3B-mediated repression of CDKN2B expression.

Numerous studies have reported the important role of microRNAs (miRNAs) in human cancers. Although abnormal miR-29b expression has been linked to tumorigenesis in several cancers, its role in cholangiocarcinoma remains largely unknown. We found that miR-29b expression is frequently downregulated in human cholangiocarcinoma QBC939 cells and in clinical tumor samples. In cholangiocarcinoma patients, low miR-29b expression predicts poor overall survival. Overexpression of miR-29b in QBC939 cells inhibited proliferation, induced G1 phase cycle arrest, and promoted apoptosis. Methylation-specific PCR (MSP) analysis revealed a decreased methylation imprint at the promoter of the cell cycle inhibitor gene CDKN2B in cells overexpressing miR-29b. After identifying the DNA methyltransferase DNMT3B as a putative miR-29b target, luciferase reporter assays confirmed a suppressive effect of miR-29b on DNMT3B expression. Accordingly, we detected an inverse correlation between miR-29b and DNMT3B expression in clinical cholangiocarcinoma specimens. In QBC939 cells, DNMT3B overexpression promoted proliferation and inhibited apoptosis. DNMT3B silencing, in turn, led to increased CDKN2B expression. We also observed significant growth arrest in subcutaneous tumors formed in nude mice by QBC939 cells overexpressing miR-29b. These findings suggest miR-29b functions as a tumor suppressor in cholangiocarcinoma by relieving DNMT3B-mediated repression of CDKN2B expression.

Experimental Study on the Coating Removing Characteristics of High-Pressure Water Jet by Micro Jet Flow.

In this paper, coating removal characteristics of water jet by micro jet flow affected by cleaning parameters is analyzed. Numerical simulation of fluid field calculates the velocity and pressure distribution of a water jet impinging on a rigid wall, which is used for design experiments of coating removal affected by jet pressure, traversal speed, and repeated impacting times. The removal width is used as a measure of water jet coating removal capability. Experiment results show that the coating removal width is constant, independent with traversal speed or repeated times when total exposure time of waterjet impingement is fixed. According to results of coating removal by a linear moving water jet, this study also analyzes characteristics of coating removal by rotating jet disc, especially residual coating affected by rotational and moving speed of the cleaning disc. The research is helpful to improve the coating removal efficiency of cleaning disc devices.

Development and Experiments of an Electrothermal Driven Deep-Sea Buoyancy Control Module.

Due to the extremely high pressures in the deep sea, heavy ballast tanks and pressure compensating hydraulic tanks are typically required to support the operation of classic buoyancy controls. Buoyancy control systems driven by phase-change materials (PCM) have unique advantages over conventional hydraulically actuated buoyancy control systems, including high adaptability for deep-sea exploration and simple, lightweight, and compact structures. Inspired by this, a buoyancy control module (BCM) was designed with flexible material as the shell. Instead of a conventional mechanical system, the device uses an electric heating drive to control buoyancy by heating and cooling the PCM. Based on the principle of pressure compensation, this device can adjust the buoyancy of a small underwater vehicle in a deep-sea high-pressure environment. The BCM successfully adjusts the buoyancy to lift itself up and down in the South China Sea at a depth of 3223 m. The performance of the phase-change BCM to control buoyancy under high pressure is validated by systematic experiments and theoretical analysis. Our work proposes a flexible scheme for the design of a deep-sea phase-change-driven BCM and highlights its potential application in deep-sea micro-mechanical systems, especially soft robots.

A Composite Fabric-Based Soft Rehabilitation Glove With Soft Joint for Dementia in Parkinson's Disease.

A kind of wearable exoskeleton soft rehabilitation glove is proposed for the dementia in Parkinson's disease (PD) patients with loss of hand function, limited range of motion, and insufficient finger muscle strength to carry out rehabilitation exercise training in a passive or auxiliary way. A novel soft joint structure based on composite fabric material is introduced for the design of the soft glove with bionic method, and experiments are conducted to verify the effeteness of the proposed soft rehabilitation glove. The test results showed that when the fluid pressure was 0.42 MPa, the joint angle of MCP, PIP and DIP could be up to 81°, 98°, 72°, and produce output torque of 1.18Nm, 1.44Nm and 1.82Nm respectively, which meets the requirements of the hand rehabilitation. A dynamic rehabilitation-training test of the rehabilitation glove was also carried out, and the results showed that the movement frequency of soft fingers could reach 30 times/min, which is sufficient for repetitive flexion/extension exercise. In order to verify the grasping characteristics of the soft glove for irregular objects, experiments were carried out. The experimental results showed that the bionic soft glove was dexterous in grasping, which conforms to the universal grasping characteristics of human hands, has the function of assisting daily life (ADL), and meets the requirements of rehabilitation.

Gear Tooth Profile Reconstruction via Geometrically Compensated Laser Triangulation Measurements.

Precision modeling of the hydraulic gear pump pressure dynamics depends on the accurate prediction of volumetric displacement in the inter-tooth spaces of the gear. By accurate reconstruction of the gear profile, detailed transient volumetric information can be determined. Therefore, this paper reports a non-contact gear measurement device using two opposing laser triangulation sensors, and the key geometrical models to reconstruct the profile with geometrical error compensation. An optimization-based key parameter calculation method is also proposed to find the unknown orientation of the sensor. Finally, an experimental setup is established, the performance of the device is tested and the geometric model is validated. Initial results showed that the method is able to reconstruct the target tooth profile and compensated results can reduce the geometrical error by up to 98% compared to the uncalibrated ones.