Prognostic models for early and late tumor progression prediction in nasopharyngeal carcinoma: An analysis of 8292 endemic cases.

OBJECTIVES: The time for posttreatment tumor progression differs between nasopharyngeal carcinoma (NPC) patients. Herein, we established effective nomograms for predicting early tumor progression (ETP) and late tumor progression (LTP) in NPC patients. METHODS: We retrospectively enrolled 8292 NPC patients (training cohort: n = 6219; validation cohort: n = 2073). The ELP and LTP were defined as the time to tumor progression ≤24 and >24 months after treatment, respectively. RESULTS: The ETP and LTP accounted for 52.6 and 47.4% of the total patient cohort, respectively. Patients who developed ETP had markedly worse overall survival (OS) versus patients who suffered from LTP (5-year OS: 26.2% vs. 59.7%, p < 0.001). Further, we identified 10/6 predictive factors significantly associated with ETP/LTP via logistic regression analyses. These indicators were used separately to construct two predictive nomograms for ETP and LTP. In the training group, the ETP nomogram [Harrell Concordance Index (C-index) value: 0.711 vs. 0.618; p < 0.001] and LTP nomogram (C-index value: 0.701 vs. 0.612; p < 0.001) were significantly superior for risk stratification than the TNM staging. These results were supported in the validation group with a C-index value of 0.753 and 0.738 for the ETP and LTP nomograms, respectively. High-risk patients defined by ETP/LTP nomograms had shorter progression-free survival than low-risk patients (all p < 0.001). CONCLUSION: The established nomograms can help in ELP or LTP risk stratification for NPC patients. Our current results might also provide insights into individualized treatment decisions and designing surveillance strategies for NPC patients.

Targeted demethylation at ZNF154 promotor upregulates ZNF154 expression and inhibits the proliferation and migration of Esophageal Squamous Carcinoma cells.

Zinc finger protein 154 (ZNF154) is hypermethylated at the promoter in many epithelial-derived solid tumors. However, its methylation status and function in esophageal squamous carcinoma (ESCC) are poorly understood. We found that the ZNF154 promoter is hypermethylated in ESCC and portends poor prognosis. In addition, ZNF154 functions as a tumor suppressor gene (TSG) in ESCC, and is downregulated by promoter hypermethylation. We established a targeted demethylation strategy based on CRISPR/dCas9 technology and found that the hypermethylation of ZNF154 promoter repressed ZNF154 induction, which in turn promoted the proliferation and migration of ESCC cells in vitro and in vivo. Finally, high-throughput CUT&Tag analysis, GEPIA software and qPCR were used to revealed the role of ZNF154 as a transcription factor to upregulate the expression of ESCC-associated tumor suppressor genes. Taken together, hypermethylation of the ZNF154 promoter plays an important role in the development of ESCC, and epigenetic editing is a promising tool for inhibiting ESCC cells with aberrant DNA methylation.

Liquid-crystal-polymer binary diffractive optical elements with a sub-micrometer feature size realized by a contact polarization holography.

In this Letter, a contact polarization holographic photoalignment method is proposed. In the holographic recording, a phase mask is contacted with a photoalignment film, making light carrying wavefront information interfere with reference light in the near-field region to realize polarization holographic pattern recording with a sub-micrometer feature size. The relevant theoretical derivation is given, and holographic recording of a 0.4 µm feature-size phase mask is realized. The proposed method can conveniently realize liquid-crystal binary diffractive optical elements with a sub-micrometer feature size. Off-axis diffraction can also be realized by superimposing the grating information by changing the angle between the substrate and the interference light.

Phase retrieval by random binary amplitude modulation and ptychography principle.

An improved binary amplitude modulation-based phase retrieval method studied by means of simulations and experiments is presented in this paper. The idea of ptychography is introduced for the purpose of designing random binary amplitude masks. The masks have the features that part of the light transmission regions is overlapped with each other and the overlapping positions are randomly distributed. The requirement for the consistency of light field in overlapping regions forms a strong constraint which is similar to the overlap constraint in ptychography. The constraint makes the iterative algorithm have high convergence accuracy in comparison to that of the original binary amplitude modulation method. Influences of amounts and overlap ratio of the modulation mask on reconstruction accuracy and speed of imaging process are analyzed. The comparison between our method and the original binary amplitude modulation method is performed in order to verify the feasibility of the proposed method.

Dual-task convolutional neural network based on the combination of the U-Net and a diffraction propagation model for phase hologram design with suppressed speckle noise.

In this paper, a dual-task convolutional neural network based on the combination of the U-Net and a diffraction propagation model is proposed for the design of phase holograms to suppress speckle noise of the reconstructed images. By introducing a Fresnel transmission layer, based on angular spectrum diffraction theory, as the diffraction propagation model and incorporating it into U-Net as the output layer, the proposed neural network model can describe the actual physical process of holographic imaging, and the distributions of both the light amplitude and phase can be generated. Afterwards, by respectively using the Pearson correlation coefficient (PCC) as the loss function to modulate the distribution of the amplitude, and a proposed target-weighted standard deviation (TWSD) as the loss function to limit the randomness and arbitrariness of the reconstructed phase distribution, the dual tasks of the amplitude reconstruction and phase smoothing are jointly solved, and thus the phase hologram that can produce high quality image without speckle is obtained. Both simulations and optical experiments are carried out to confirm the feasibility and effectiveness of the proposed method. Furthermore, the depth of field (DOF) of the image using the proposed method is much larger than that of using the traditional Gerchberg-Saxton (GS) algorithm due to the smoothness of the reconstructed phase distribution, which is also verified in the experiments. This study provides a new phase hologram design approach and shows the potential of neural networks in the field of the holographic imaging and more.

Fabrication of Multifocal Microlens Array by One Step Exposure Process.

Microlenses can be widely used in integrated micro-optical systems. However, in some special applications, such as light field imaging systems, multifocal microlens arrays (MLA) are expected to improve imaging resolution. For the fabrication of multifocal MLA, the traditional fabrication method is no longer applicable. To solve this problem, a fabrication method of multifocal MLA by a one step exposure process is proposed. Through the analyses and research of photoresist AZ9260, the nonlinear relationship between exposure dose and exposure depth is established. In the design of the mask, the mask pattern is corrected according to the nonlinear relationship to obtain the final mask. The continuous surface of the multifocal MLA is fabricated by the mask moving exposure. The experimental results show that the prepared multifocal MLA has high filling factor and surface fidelity. What is more, this method is simple and efficient to use in practical applications.

Integrated Double-Sided Random Microlens Array Used for Laser Beam Homogenization.

Double microlens arrays (MLAs) in series can be used to divide and superpose laser beam so as to achieve a homogenized spot. However, for laser beam homogenization with high coherence, the periodic lattice distribution in the homogenized spot will be generated due to the periodicity of the traditional MLA, which greatly reduces the uniformity of the homogenized spot. To solve this problem, a monolithic and highly integrated double-sided random microlens array (D-rMLA) is proposed for the purpose of achieving laser beam homogenization. The periodicity of the MLA is disturbed by the closely arranged microlens structures with random apertures. And the random speckle field is achieved to improve the uniformity of the homogenized spot by the superposition of the divided sub-beams. In addition, the double-sided exposure technique is proposed to prepare the rMLA on both sides of the same substrate with high precision alignment to form an integrated D-rMLA structure, which avoids the strict alignment problem in the installation process of traditional discrete MLAs. Then the laser beam homogenization experiments have been carried out by using the prepared D-rMLA structure. The laser beam homogenized spots of different wavelengths have been tested, including the wavelengths of 650 nm (R), 532 nm (G), and 405 nm (B). The experimental results show that the uniformity of the RGB homogenized spots is about 91%, 89%, and 90%. And the energy utilization rate is about 89%, 87%, 86%, respectively. Hence, the prepared structure has high laser beam homogenization ability and energy utilization rate, which is suitable for wide wavelength regime.

Research on Dynamic Evolution Model and Method of Communication Network Based on Real War Game.

Based on the data in real combat games, the combat System-of-Systems is usually composed of a large number of armed equipment platforms (or systems) and a reasonable communication network to connect mutually independent weapons and equipment platforms to achieve tasks such as information collection, sharing, and collaborative processing. However, the generation algorithm of the combat system in the existing research is too simple and not suitable for reality. To overcome this problem, this paper proposes a communication network generation algorithm by adopting the joint distribution strategy of power law distribution and Poisson distribution to model the communication network. The simulation method is used to study the operation under continuous attack on communication nodes. The comprehensive experimental results of the dynamic evolution of the combat network in the battle scene verify the rationality and effectiveness of the communication network construction.

A novel cell-free DNA methylation-based model improves the early detection of colorectal cancer.

Screening for early-stage disease is vital for reducing colorectal cancer (CRC)-related mortality. Methylation of circulating tumor DNA has been previously used for various types of cancer screening. A novel cell-free DNA (cfDNA) methylation-based model which can improve the early detection of CRC is warranted. For our study, we collected 313 tissue and 577 plasma samples from patients with CRC, advanced adenoma (AA), non-AA and healthy controls. After quality control, 187 tissue DNA samples (91 non-malignant tissue from CRC patients, 26 AA and 70 CRC) and 489 plasma cfDNA samples were selected for targeted DNA methylation sequencing. We further developed a cfDNA methylation model based on 11 methylation biomarkers for CRC detection in the training cohort (area under curve [AUC] = 0.90 (0.85-0.94]) and verified the model in the validation cohort (AUC = 0.92 [0.88-0.96]). The cfDNA methylation model robustly detected patients pre-diagnosed with early-stage CRC (AUC = 0.90 [0.86-0.95]) or AA (AUC = 0.85 [0.78-0.91]). Here we established and validated a non-invasive cfDNA methylation model based on 11 DNA methylation biomarkers for the detection of early-stage CRC and AA. The utilization of the model in clinical practice may contribute to the early diagnosis of CRC.

Development of a Nomogram Model for Treatment of Nonmetastatic Nasopharyngeal Carcinoma.

Importance: Because of tumor heterogeneity, overall survival (OS) differs significantly among individuals with nasopharyngeal carcinoma (NPC), even among those with the same clinical stage. Relying solely on TNM staging to guide treatment remains imperfect. Objectives: To establish a comprehensive nomogram to estimate individualized OS and to explore stratified treatment regimens for risk subgroups in nonmetastatic NPC. Design, Setting, and Participants: This cohort study included 8093 patients diagnosed with NPC at a single center in China from April 2009 to December 2015. The sample was split into a training cohort (5398 participants [66.7%]) and validation cohort (2695 [33.3%]). Data were analyzed in May 2020. Exposures: Age, T stage, N stage, Epstein-Barr virus (EBV) DNA level, serum lactate dehydrogenase (LDH) levels, and albumin (ALB) levels. Main Outcomes and Measures: The primary end point was OS. The nomogram for estimating OS was generated based on multivariate Cox proportional hazards regression. The performance of the nomogram was quantified using Harrell concordance index (C index), the area under the curve (AUC) of the receiver operating characteristic curve, and a calibration curve. OS rates were established using the Kaplan-Meier method, and intersubgroup differences were examined by the log-rank test. Results: Among the 8093 participants, 5688 (70.3%) were men, and the median age at diagnosis was 45 years (range, 7-85 years). Six variables (age, T stage, N stage, EBV DNA levels, LDH levels, and ALB levels) were identified through multivariate Cox regression and incorporated into a nomogram to estimate OS. The resulting nomogram showed excellent discriminative ability and significantly outperformed the eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control TNM staging system for estimating OS (C index, 0.716 [95% CI, 0.698-0.734] vs 0.643 [95% CI, 0.624-0.661]; P < .001; AUC, 0.717 [95% CI, 0.698-0.737] vs 0.643 [95% CI, 0.623-0.662]; P < .001), and the calibration curves showed satisfactory agreement between the actual and nomogram-estimated OS rates. The validation cohort confirmed the results. Patients were stratified into 4 risk groups based on the 25th, 50th, and 75th percentile score values estimated from the nomogram. The 4 nomogram-defined risk groups demonstrated significantly different intergroup OS (3-year OS rates: risk group 1, 1328 of 1345 [98.7%]; risk group 2, 1289 of 1341 [96.1%]; risk group 3, 1222 of 1321 [92.5%]; risk group 4, 1173 of 1391 [84.3%]; P < .001). These risk groups were associated with the efficacy of different treatment regimens. For example, for risk group 4, induction chemotherapy with concurrent chemoradiotherapy was associated with a significantly better OS than concurrent chemoradiotherapy (log-rank P = .008) and intensity-modulated radiotherapy alone (log-rank P < .001). Conclusions and Relevance: In this study, the proposed nomogram model enabled individualized prognostication of OS and could help to guide risk-adapted treatment for patients with nonmetastatic NPC.

Error tracking-control-reduction algorithm for designing diffractive optical element with high image reconstruction quality.

The use of the diffractive optical element (DOE) can often significantly reduce the size and enhance the performance of the optical system, but it is mostly prevented by low diffraction efficiency and serious speckle noise due to the quantization error. In this paper, an error tracking-control-reduction (ETCR) algorithm is proposed to suppress the quantization error, which adjusts the accumulative action, controls the current state and predicts the trend of the error. The simulation and experiment results verify that the ETCR algorithm has high diffraction efficiency which can be comparable with the Gerchberg-Saxton (GS) and Modified GS algorithms. Furthermore, the root-mean-square error (RMSE) of the proposed algorithm is significantly lower than that of the GS and MGS algorithms. Based on the proposed method, a 2-level DOE has been designed and fabricated to generate several grey images with only 0.05 RMSE.

Fabrication of Random Microlens Array for Laser Beam Homogenization with High Efficiency.

The miniaturized and integrated microlens array (MLA) can effectively achieve the beam homogenization, compactness and miniaturization of laser systems. When the high-coherence laser beam is homogenized by means of using the MLA, interference fringes will occur in the homogenized light spot due to the periodicity of the MLA, which seriously affects the uniformity of the homogenized light spot. To solve this problem, a novel random microlens array (rMLA) structure was proposed for the purpose of achieving beam homogenization. The coherence in the homogenization process is suppressed by means of breaking the periodicity of the MLA. The homogenized light spot with a high energy utilization is then obtained accordingly. In the fabrication process, a clever method of combining chemical etching with lithography technology is performed to fabricate a honeycomb rMLA and a rectangular rMLA. The experimental results show that the energy utilization rate of the two types of the rMLAs is about 90%, and the uniformity of the homogenized light spots generated by the honeycomb rMLA and the rectangular rMLA are more than 80% and 85%, respectively. Meanwhile, fully cost-effective fabrication is possible to be realized.

Development and validation of a prognostic nomogram for the pre-treatment prediction of early metachronous metastasis in endemic nasopharyngeal carcinoma: a big-data intelligence platform-based analysis.

BACKGROUND: Early failure of cancer treatment generally indicates a poor prognosis. Here, we aim to develop and validate a pre-treatment nomogram to predict early metachronous metastasis (EMM) in nasopharyngeal carcinoma (NPC). METHODS: From 2009 to 2015, a total of 9461 patients with NPC (training cohort: n = 7096; validation cohort: n = 2365) were identified from an institutional big-data research platform. EMM was defined as time to metastasis within 2 years after treatment. Early metachronous distant metastasis-free survival (EM-DMFS) was the primary endpoint. A nomogram was established with the significant prognostic factors for EM-DMFS determined by multivariate Cox regression analyses in the training cohort. The Harrell Concordance Index (C-index), area under the receiver operator characteristic curve (AUC), and calibration curves were applied to evaluate this model. RESULTS: EMM account for 73.5% of the total metachronous metastasis rate and is associated with poor long-term survival in NPC. The final nomogram, which included six clinical variables, achieved satisfactory discriminative performance and significantly outperformed the traditional tumor-node-metastasis (TNM) classification for predicting EM-DMFS: C-index: 0.721 versus 0.638, p < 0.001; AUC: 0.730 versus 0.644, p < 0.001. The calibration curves showed excellent agreement between the predicted and actual EM-DMFS. The nomogram can stratify patients into three risk groups with distinct EM-DMFS (2-year DMFS: 96.8% versus 90.1% versus 80.3%, p < 0.001). A validation cohort supported the results. The three identified risk groups are correlated with the efficacy of different treatment regimens. CONCLUSION: Our established nomogram can reliably predict EMM in patients with NPC and might aid in formulating risk-adapted treatment decisions and personalized patient follow-up strategies.

Effective method for further magnifying the image in holographic projection under divergent light illumination.

Divergent light illumination can effectively increase the diffraction angle of holographic projection. However, the achieved maximum image size is limited to the geometric enlargement of the hologram size with the existing double-sampling Fresnel diffraction algorithm. In this paper, an effective method for further magnifying the image is proposed. The theoretical maximum size under divergent illumination is first analyzed. On this basis, a virtual intermediate plane is introduced between the source plane and the image plane. Then three-step diffraction calculation is performed to evaluate the Fresnel diffraction between the hologram plane and the image plane so that the sampling interval on the image plane is related to the position of the virtual plane and can be flexibly tuned. Consequently, the achieved image size can be further enlarged. The feasibility of the proposed method is demonstrated by simulations and experiments.

Design and Fabrication of Flexible Naked-Eye 3D Display Film Element Based on Microstructure.

The naked-eye three-dimensional (3D) display technology without wearing equipment is an inevitable future development trend. In this paper, the design and fabrication of a flexible naked-eye 3D display film element based on a microstructure have been proposed to achieve a high-resolution 3D display effect. The film element consists of two sets of key microstructures, namely, a microimage array (MIA) and microlens array (MLA). By establishing the basic structural model, the matching relationship between the two groups of microstructures has been studied. Based on 3D graphics software, a 3D object information acquisition model has been proposed to achieve a high-resolution MIA from different viewpoints, recording without crosstalk. In addition, lithography technology has been used to realize the fabrications of the MLA and MIA. Based on nanoimprint technology, a complete integration technology on a flexible film substrate has been formed. Finally, a flexible 3D display film element has been fabricated, which has a light weight and can be curled.

m6A methyltransferase METTL3 suppresses colorectal cancer proliferation and migration through p38/ERK pathways.

Purpose: Although many biological processes are involved in the modification of N6-methyladenosine (m6A), the exact role of m6A in the development of malignant tumors remains unclear. Methyltransferase 3 (METTL3) is a major RNA N6-methyladenosine methyltransferase. We aimed to explore the role of METTL3 in colorectal cancer (CRC) carcinogenesis and disease progression. Methods: In this study, immunohistochemistry was performed with a tissue microarray. qRT-PCR and Western blots were used to evaluate the expression of METTL3 in CRC cells. The effect of METTL3 on cell proliferation, migration and invasion of CRC cells was examined by IncuCyte Live Cell Analysis System and transwell assay, respectively. Results: The results suggested that positive expression of METTL3 was significantly associated with longer survival time (P=0.011). We next demonstrated that overexpression of METTL3 could inhibit proliferation, migration and invasion in CRC cells, while downregulation of METTL3 shows the opposite result. Furthermore, downregulation of METTL3 resulted in activation of p-p38 and p-ERK. Moreover, the inhibitors of p38 or ERK kinase could significantly reverse the effect of migration and invasion, which was induced by knockdown of METTL3. Conclusion: We concluded that METTL3 played a tumor-suppressive role in CRC cell proliferation, migration and invasion through p38/ERK pathways, which indicated that METTL3 might be a novel marker for CRC carcinogenesis, progression and survival.

Reconfigurable step-zoom metalens without optical and mechanical compensations.

A polarization-dependent metasurface that consists of nanobrick arrays with spatial varying dimensions in two orthogonal directions has shown independent phase control ability, which paves a new way to design a reconfigurable step-zoom lens with two different focal lengths depending on the polarization states of an incident beam. In this paper, we report a highly integrated step-zoom metalens with dual focal lengths based on double-sided metasurfaces sitting on a transparent substrate. By assigning the focal power and balancing the aberrations between the front and rear metasurfaces, a large field-of-view ( ± 20°) step-zoom metalens corrected for monochromatic aberrations was designed, and its high performance (nearly diffraction-limited image quality for both on-axis and off-axis imaging) was verified by full-wave numerical simulations. More interestingly, the image plane of the designed metalens keeps unchanged after the zoom switching, which will bring great convenience for practical applications. With the advantages such as ultra-compactness, flexibility, and simplicity, the proposed metalens indicates the potential in the fields that require highly integrated zoom imaging and beam focusing without optical and mechanical compensations.

Design and Fabrication of an Artificial Compound Eye for Multi-Spectral Imaging.

The artificial compound eye (ACE) structure is a new type of miniaturized, lightweight and intelligent imaging system. This paper has proposed to design a multi-spectral ACE structure to enable the structure to achieve multi-spectral information on the basis of imaging. The sub-eyes in the compound eye structure have been designed as diffractive beam splitting lenses with the same focal length of 20 mm, but with the different designed center wavelengths of 650 nm, 532 nm, and 445 nm, respectively. The proximity exposure lithography and reactive ion etching process were used to prepare the designed multi-spectral ACE structure, and the spectral splitting and multi-spectral imaging experiments were carried out to verify the multi-spectral imaging function of the structure without axial movement. Furthermore, the structure can be designed according to actual requirements, which can be applied to covert reconnaissance, camouflage identification, gas leakage or other fields.

Engulfment and Cell Motility Protein 1 Protects Against DSS-induced Colonic Injury in Mice via Rac1 Activation.

BACKGROUND AND AIMS: Mucosal healing is an emerging therapeutic goal that could result in clinical remission of inflammatory bowel disease [IBD]. We sought to determine the role of engulfment and cell motility protein 1 [ELMO1] in wound healing in vitro and in vivo and to investigate the underlying pathways. METHODS: RNA transcriptome sequencing was performed to detect the expression profiles of mRNA between inflamed tissues and corresponding non-inflamed tissues of IBD patients, followed by Gene Expression Omnibus [GEO] datasets and western blot analysis. The effects of ELMO1 overexpression or knockdown on cell migration and proliferation were determined. The dependence of these effects on Rac1 was assessed using a Rac1 inhibitor [NSC23766] and a Rac1 pull-down assay. We identified the underlying pathways involved by Gene Ontology [GO] analysis. A dextran sulphate sodium [DSS]-induced colitis model was established to evaluate the role of ELMO1 in colonic mucosal healing. RESULTS: ELMO1 was upregulated in inflamed tissues compared with corresponding non-inflamed tissues. ELMO1 overexpression increased cell migration in a Rac1-dependent manner. Depletion of ELMO1, or NSC23766 administration, abolished this effect. GO analysis revealed that ELMO1 overexpression preferentially affected pathways involved in cytoskeletal regulation and wound healing, which was demonstrated by enhanced F-actin staining and increased numbers of extending lamellipodia in cells overexpressing ELMO1. In DSS-induced colitis, systemic delivery of pSin-EF2-ELMO1-Pur attenuated colonic inflammation and promoted recovery from colonic injury. The protective effect of ELMO1 was dependent on Rac1 activation. CONCLUSIONS: ELMO1 protects against DSS-induced colonic injury in mice through its effect on epithelial migration via Rac1 activation.

Fabrication of Random Microwell Arrays as Pseudo-Thermal Speckle Light Source.

Quantum correlated imaging using the intensity fluctuations of thermal light possesses advantages of high resolution and strong anti-interference ability. The common method to produce pseudo-thermal light source is using a rotary ground glass and transmission of laser beam. In the present work, we propose a method for the fabrication of microwell arrays with randomly varied diameters, which could be used as a new structural element for pseudo-thermal speckle light source. If these are etched with random sizes then they may also have random and complex varying curvatures (diffusion limited etching) leading to random destructive interference of the coherent beam which could be a good thing. The microwell arrays, with diameters randomly varying from 5 µm to 40 µm, height varying from 200 nm to 20 µm, were fabricated by photolithography combined with acid etching. The experimental conditions are simple and can be scaled up to for large structures. The produced microwell arrays can transform the laser beam to a pseudo-thermal light source with a certain divergent angle by rational designing of mask and adjustable process parameters.