Our study aimed to investigate whether CAF (cancer-associated fibroblasts) were involved in long noncoding RNAs (lncRNA)-regulated radioresponse in esophageal squamous cell carcinoma (ESCC).
By use ...of lncRNAs PCR array, 38 lncRNAs were screened in esophageal cancer cells and in normal esophageal epithelial cells Het-1A. LncRNA DNM3OS was detected in tumor tissues of patients with ESCC and in matched normal esophageal epithelial tissues by qRT-PCR analysis and
hybridization assay. The association of DNM3OS and tumor radioresistance was investigated
and
. The influences of DNM3OS on DNA damage response (DDR) was investigated by Western blotting, immunofluorescence imaging, and comet assay. The mechanisms by which CAFs promoted DNM3OS expression was investigated by kinase inhibitors' screening, luciferase assay, and chromatin immunoprecipitation.
Among the 38 lncRNAs tested, DNM3OS was found to have a much higher expression level in esophageal cancer cells than in Het-1A. In tumor tissues of 16 patients with ESCC, the expression level of DNM3OS showed an average increase of 6.3429-fold compared with that in matched normal tissues. DNM3OS conferred significant radioresistance
and
by regulating DDR. CAFs promoted the expression of DNM3OS with a 39.2554-fold and 38.3163-fold increase in KYSE-30 and KYSE-140, respectively. CAFs promoted the expression of DNM3OS in a PDGFβ/PDGFRβ/FOXO1 signaling pathway-dependent manner. FOXO1, a transcription factor downstream of PDGFβ/PDGFRβ signaling pathway, initiated the transcription of DNM3OS by binding to DNM3OS promoter.
Our study highlighted CAF-promoted DNM3OS as an attractive target to reverse tumor radioresistance in ESCC.
Five-year survival rate of esophageal squamous cell carcinoma (ESCC) patients treated with radiotherapy is <20%. Our study aimed to investigate whether cancer-associated fibroblasts (CAFs), one major ...component of tumor microenvironment, were involved in tumor radioresistance in ESCC. By use of human chemokine/cytokine array, human chemokine CXCL1 was found to be highly expressed in CAFs compared with that in matched normal fibroblasts. Inhibition of CXCL1 expression in CAFs significantly reversed CAF-conferred radioresistance in vitro and in vivo. CAF-secreted CXCL1 inhibited the expression of reactive oxygen species (ROS)-scavenging enzyme superoxide dismutase 1, leading to increased ROS accumulation following radiation, by which DNA damage repair was enhanced and the radioresistance was mediated. CAF-secreted CXCL1 mediated the radioresistance also by activation of Mek/Erk pathway. The cross talk of CAFs and ESCC cells induced CXCL1 expression in an autocrine/paracrine signaling loop, which further enhanced tumor radioresistance. Together, our study highlighted CAF-secreted CXCL1 as an attractive target to reverse tumor radioresistance and can be used as an independent prognostic factor of ESCC patients treated with chemoradiotherapy.
Tumor heterogeneity of human colorectal cancer (CRC)-initiating cells (CRCICs) in cancer tissues often represents aggressive features of cancer progression. For high-resolution examination of CRCICs, ...we performed single-cell whole-exome sequencing (scWES) and bulk cell targeted exome sequencing (TES) of CRCICs to investigate stemness-specific somatic alterations or clonal evolution.
Single cells of three subpopulations of CRCICs (CD133+CD44+, CD133−CD44+, and CD133+CD44− cells), CRC cells (CRCCs), and control cells from one CRC tissue were sorted for scWES. Then, we set up a mutation panel from scWES data and TES was used to validate mutation distribution and clonal evolution in additional 96 samples (20 patients) those were also sorted into the same three groups of CRCICs and CRCCs. The knock-down experiments were used to analyze stemness-related mutant genes. Neoantigens of these mutant genes and their MHC binding affinity were also analyzed.
Clonal evolution analysis of scWES and TES showed that the CD133+CD44− CRCICs were the likely origin of CRC before evolving into other groups of CRCICs/CRCCs. We revealed that AHNAK2, PLIN4, HLA-B, ALK, CCDC92 and ALMS1 genes were specifically mutated in CRCICs followed by the validation of their functions. Furthermore, four predicted neoantigens of AHNAK2 were identified and validated, which might have applications in immunotherapy for CRC patients.
All the integrative analyses above revealed clonal evolution of CRC and new markers for CRCICs and demonstrate the important roles of CRCICs in tumorigenesis and progression of CRCs.
A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.
The noncontact optical probe-based surface scanning is promising for the measurement of complex-shaped optical surfaces. In this study, by combining a chromatic confocal sensor and a planar ...nano-positioning stage, a sub-aperture scanning and stitching method is developed for the noncontact measurement of the microstructured optical surfaces, with the measured form accuracy being irrespective of the accuracy of the global scanning stage. After the scanning, the Gaussian process-based denoising is employed to remove the measurement noises, and a hybrid registration algorithm is proposed to achieve a 6-DOF alignment of any neighbored sub-apertures. For the registration, the differential evolution-based minimization is implemented to find a coarse transformation which then serves as the initial value for the iterative closest point-based fine registration. The hybrid method is beneficial in finding an optimal registration with a greatly reduced computation burden. Finally, the effectiveness of the developed measurement system, as well as the stitching algorithm, is comprehensively demonstrated through practically measuring a sinusoidal micro-grid surface.
COVID-19 broke out in 2019, seriously affecting people’s health and life. Recent studies have indicated that radiological images carry crucial information about COVID-19. Hence, automatic image ...classification assisted by artificial intelligence (AI) can be employed as a potential diagnostic tool. Nonetheless, in the task of COVID-19 X-ray image recognition, there are local features, including local vascular dilatation, as well as global features, including large ground glass-like shadows, traditional deep neural networks cannot effectively extract features, and the significance of distinct scale features for the task is also divergent, feature element-wise adding or feature concatenating to fuse features from various branches do not consider the internal correlation between features. In view of the above problems, we propose a Correlation-based Multi-scale Feature Fusion Network (CMFuse), combining the advantages of Convolutional Neural Network (CNN) and Transformer. The model captures local spatial contextual features and global semantic information representation of features at different scales in parallel, and the extracted features are adaptively fused at distinct levels through the feature fusion module, down-sampling and other steps to obtain the final classification results. We evaluated CMFuse on the integrated COVID-19 X-ray image dataset, and the results showed that our model attains 97.36
%
Accuracy, 99.15
%
Specificity, 97.27
%
Recall, 97.17
%
Precision, and 97.22
%
F1-score, which outperforms other previous related works.
The measurement of five degrees-of-freedom (5-DOF) error motions, including radial, axial, and tilt motions, is crucial for ultra-precision rotary axes, which are key components of ultra-precision ...machine tools and instrumentation. In this study, we propose an interference-enhanced micro-vision technique to concurrently derive the 5-DOF error motions from a single-shot two-dimensional image, which was captured by a standard industrial camera equipped with an interference objective lens. By consolidating the essential features into a single optical path, the interference-enhanced micro-vision technique ingeniously merges machine micro-vision and modified white-light interference to detect in-plane and out-of-plane motions. Numerical simulations demonstrated, the basic principle for deriving the 5-DOF error motions, and the magnification of objective lens had inconsistent effects on the measurement accuracy for the radial and tilt motions, i.e. higher magnification led to higher radial accuracy but lower tilt accuracy. As practical application, the error motion detection capability was demonstrated by simultaneously measuring the 5-DOF synchronous and asynchronous error motions for a typical air bearing spindle at rotation speeds of 8.33, 108.33, and 308.33 rpm. The synchronous errors were nearly identical at various spindle speeds. However, because of system dynamics, increased vibrations were observed to be superimposed on the basic tilt error motions as the spindle speeds increased, which were verified by the vibration marks imprinted on the turned surfaces. For the 5-DOF motion measurements, the least-square fitting using large-volume edge and greyscale data of the captured image enabled super-high resolutions, despite using a camera with a relatively large pixel size and low bit depth. These results demonstrate that the proposed interference-enhanced micro-vision technique is a simple and effective tool for measuring spatial error motions in ultra-precision rotary axes.
•Novel interference-enhanced micro-vision technique is proposed by incorporating white-light interference into micro-machine vision.•The interference-enhanced micro-vision enables the simultaneous measurement of five degrees-of-freedom error motions from a single-shot image for ultra-precision rotary axes.•A method for reconstructing linear/tilt motion with sub-nanometric/nanoradian resolution is proposed.•The systematic errors are transformed into first harmonics for easy removal.•An extended sampling strategy is demonstrated for measuring high-speed spindles using low frame rates.
Chromatic confocal sensor-based on-machine measurement is effective for identifying and compensating for form errors of the ultra-precisely machined components. In this study, an on-machine ...measurement system was developed for an ultra-precision diamond turning machine to generate microstructured optical surfaces, for which the sensor probe adopts a uniform spiral scanning motion. To avoid the tedious spiral center alignment, a self-alignment method was proposed without additional equipment or artefact, which identified the deviation of the optical axis to the spindle axis by matching the measured surface points and the designed surface. The feasibility of the proposed method was demonstrated by numerical simulation with full consideration of noises and system dynamics. Practically, taking a typical microstructured surface as an example, the on-machine measured points were reconstructed after calibrating the alignment deviation, which was then verified by off-machine white light interferometry measurement. Avoiding tedious operations and special artefacts may significantly simplify the on-machine measurement process, thereby greatly improving the efficiency and flexibility for the measurement.
Establishing efficient and accurate analytical models for the normal-stressed electromagnetic actuators (NSEAs) is crucial for optimizing the magnetic stages to achieve desired working performance. ...To overcome the challenges of existing electromagnetic models for NSEAs, a parametric equivalent magnetic network model with adaptive meshes was developed for the designed NSEA stage, which fully included the nonlinear flux leakage, magnetic saturation, and material nonlinearity. Thereafter, by combining a mechanical model for the compliant bearing, an electromagnetic-mechanical coupling optimization method with multiple constraints was proposed for the stage to achieve a millimeter-range motion with a maximized natural frequency. As for the optimized stage, the electromagnetic actuation and bearing performance were then comprehensively verified by finite element analysis. The optimized prototype was tested to have a stroke of around <inline-formula><tex-math notation="LaTeX">\pm </tex-math></inline-formula>1016.2 <inline-formula><tex-math notation="LaTeX">\boldsymbol{\mu }</tex-math></inline-formula>m and a resonant frequency of 308 Hz, which agreed well with the theoretical design. Compared with the state-of-the-art stages with similar strokes, the developed normal-stressed electromagnetic stage has a much higher natural frequency.
This paper reports on the development of a piezo-actuated nanometric ultra-fast tool servo (NU-FTS) for nanocutting. For motion guidance, a flexure mechanism is especially designed using a novel kind ...of generalized flexure hinges with the notch profiles described by a rational Bezier curve. Both kinematics and dynamics properties of the mechanism are comprehensively modeled through a novel finite beam modeling method. With this model, the hinge is divided into a set of serially connected beams with constant cross sections. The equivalent stiffness and lumped moving mass of the mechanism are derived based on the Euler-Bernoulli beam theory. Taking advantage of the structure and performance model, the notch shape as well as the dimensions are optimized to achieve the specified criteria for the NU-FTS. Performance of the designed mechanism is verified through both finite-element analysis and practical testing on a prototype. Overall, the NU-FTS is demonstrated to have a stroke of 6 and 1.2 <inline-formula><tex-math notation="LaTeX"> \mu </tex-math></inline-formula>m for the quasi-static and 10 kHz driving condition, respectively. Through dynamics inversion-based trajectory preshaping, a maximum following error around 25 and 50 nm is obtained for tracking a simple harmonic and a complicated trajectory, respectively.
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