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BACKGROUND: Herba Patriniae and Coix seed (HC) constitute a widely utilized drug combination in the clinical management of colorectal cancer (CRC) that is known for its diuretic, anti-inflammatory, and swelling-reducing properties. Although its efficacy has been demonstrated in a clinical setting, the active compounds and their mechanisms of action in CRC treatment remain to be fully elucidated. AIM: To identify the active, CRC-targeting components of HC and to elucidate the mechanisms of action involved. METHODS: Active HC components were identified and screened using databases. Targets for each component were predicted. CRC-related targets were obtained from human gene databases. Interaction targets between HC and CRC were identified. A "drug-ingredient-target" network was created to identify the core components and targets involved. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to elucidate the key pathways involved. Molecular docking between core targets and key components was executed. In vitro experiments validated core monomers. RESULTS: Nineteen active components of HC were identified, with acacetin as the primary active compound. The predictive analysis identified 454 targets of the active compounds in HC. Intersection mapping with 2685 CRC-related targets yielded 171 intervention targets, including 30 core targets. GO and KEGG analyses indicated that HC may influence the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Molecular docking showed that acacetin exhibited an optimal interaction with AKT1, identifying PI3K, AKT, and P53 as key genes likely targeted by HC during CRC treatment. Acacetin inhibited HT-29 cell proliferation and migration, as well as promoted apoptosis, in vitro. Western blotting analysis revealed increased p53 and cleaved caspase-3 expression and decreased levels of p-PI3K, p-Akt, and survivin, which likely contributed to CRC apoptosis. CONCLUSION: Acacetin, the principal active compound in the HC pair, inhibited the proliferation and migration of HT-29 cells and promoted apoptosis through the PI3K/Akt/p53 signaling pathway.
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Catalytic oxidation of benzyl C-H bonds and sulfides from fuel oils stands as an attractive proposition in the quest for clean energy, yet their simultaneous oxidation with a singular, economically friendly catalyst is not well established. In this work, the combination of a cobalt(II) porphyrin ligand with 2-pyridinecarboxaldehyde and ZnII yielded a Zn8L6 cage (Co cube). The three-dimensional conjugated structure effectively enhances energy transfer efficiency, enabling the Co cube to show a good ability to activate oxygen under light conditions for photooxidation. Moreover, this catalytic system demonstrates high selectivity for the photocatalytic oxidation of C(sp3)-H bonds and sulfides, employing the Co cube as a single component catalyst, molecular oxygen as the oxidant, and activating oxygen into 1O2 under mild reaction conditions. This provides significant insights for organic synthesis and future design of photocatalysts with complex molecular components.
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PURPOSE: Pelvic bone segmentation and landmark definition from computed tomography (CT) images are prerequisite steps for the preoperative planning of total hip arthroplasty. In clinical applications, the diseased pelvic anatomy usually degrades the accuracies of bone segmentation and landmark detection, leading to improper surgery planning and potential operative complications. METHODS: This work proposes a two-stage multi-task algorithm to improve the accuracy of pelvic bone segmentation and landmark detection, especially for the diseased cases. The two-stage framework uses a coarse-to-fine strategy which first conducts global-scale bone segmentation and landmark detection and then focuses on the important local region to further refine the accuracy. For the global stage, a dual-task network is designed to share the common features between the segmentation and detection tasks, so that the two tasks mutually reinforce each other's performance. For the local-scale segmentation, an edge-enhanced dual-task network is designed for simultaneous bone segmentation and edge detection, leading to the more accurate delineation of the acetabulum boundary. RESULTS: This method was evaluated via threefold cross-validation based on 81 CT images (including 31 diseased and 50 healthy cases). The first stage achieved DSC scores of 0.94, 0.97, and 0.97 for the sacrum, left and right hips, respectively, and an average distance error of 3.24 mm for the bone landmarks. The second stage further improved the DSC of the acetabulum by 5.42%, and this accuracy outperforms the state-of-the-arts (SOTA) methods by 0.63%. Our method also accurately segmented the diseased acetabulum boundaries. The entire workflow took ~ 10 s, which was only half of the U-Net run time. CONCLUSION: Using the multi-task networks and the coarse-to-fine strategy, this method achieved more accurate bone segmentation and landmark detection than the SOTA method, especially for diseased hip images. Our work contributes to accurate and rapid design of acetabular cup prostheses.
Subject(s)
Deep Learning , Humans , Tomography, X-Ray Computed/methods , Hip , Pelvis/diagnostic imaging , Acetabulum , Image Processing, Computer-Assisted/methodsABSTRACT
Objective.Precise hip joint morphometry measurement from CT images is crucial for successful preoperative arthroplasty planning and biomechanical simulations. Although deep learning approaches have been applied to clinical bone surgery planning, there is still a lack of relevant research on quantifying hip joint morphometric parameters from CT images.Approach.This paper proposes a deep learning workflow for CT-based hip morphometry measurement. For the first step, a coarse-to-fine deep learning model is designed for accurate reconstruction of the hip geometry (3D bone models and key landmark points). Based on the geometric models, a robust measurement method is developed to calculate a full set of morphometric parameters, including the acetabular anteversion and inclination, the femoral neck shaft angle and the inclination, etc. Our methods were validated on two datasets with different imaging protocol parameters and further compared with the conventional 2D x-ray-based measurement method.Main results. The proposed method yields high bone segmentation accuracies (Dice coefficients of 98.18% and 97.85%, respectively) and low landmark prediction errors (1.55 mm and 1.65 mm) on both datasets. The automated measurements agree well with the radiologists' manual measurements (Pearson correlation coefficients between 0.47 and 0.99 and intraclass correlation coefficients between 0.46 and 0.98). This method provides more accurate measurements than the conventional 2D x-ray-based measurement method, reducing the error of acetabular cup size from over 2 mm to less than 1 mm. Moreover, our morphometry measurement method is robust against the error of the previous bone segmentation step. As we tested different deep learning methods for the prerequisite bone segmentation, our method produced consistent final measurement results, with only a 0.37 mm maximum inter-method difference in the cup size.Significance. This study proposes a deep learning approach with improved robustness and accuracy for pelvis arthroplasty planning.
Subject(s)
Arthroplasty, Replacement, Hip , Deep Learning , Hip Prosthesis , Arthroplasty, Replacement, Hip/methods , Workflow , Tomography, X-Ray Computed/methods , Hip Joint/diagnostic imagingABSTRACT
The characterization and evaluation of skin tissue structures are crucial for dermatological applications. Recently, Mueller matrix polarimetry and second harmonic generation microscopy have been widely used in skin tissue imaging due to their unique advantages. However, the features of layered skin tissue structures are too complicated to use a single imaging modality for achieving a comprehensive evaluation. In this study, we propose a dual-modality imaging method combining Mueller matrix polarimetry and second harmonic generation microscopy for quantitative characterization of skin tissue structures. It is demonstrated that the dual-modality method can well divide the mouse tail skin tissue specimens' images into three layers of stratum corneum, epidermis, and dermis. Then, to quantitatively analyze the structural features of different skin layers, the gray level co-occurrence matrix is adopted to provide various evaluating parameters after the image segmentations. Finally, to quantitatively measure the structural differences between damaged and normal skin areas, an index named Q-Health is defined based on cosine similarity and the gray-level co-occurrence matrix parameters of imaging results. The experiments confirm the effectiveness of the dual-modality imaging parameters for skin tissue structure discrimination and assessment. It shows the potential of the proposed method for dermatological practices and lays the foundation for further, in-depth evaluation of the health status of human skin.
Subject(s)
Collagen , Second Harmonic Generation Microscopy , Humans , Animals , Mice , Collagen/chemistry , Skin , Diagnostic Imaging , Spectrum AnalysisABSTRACT
In this paper, we propose a smartphone-based biosensor for detecting human total hemoglobin concentration in vivo with high accuracy. Compared to the existing biosensors used to measure hemoglobin concentration, the smartphone-based sensor utilizes the camera, memory, and computing power of the phone. Thus, the cost is largely reduced. Compared to existing smartphone-based sensors, we developed a highly integrated multi-wavelength LED module and a specially designed phone fixture to reduce spatial errors and motion artifacts, respectively. In addition, we embedded a new algorithm into our smartphone-based sensor to improve the measurement accuracy; an L*a*b* color space transformation and the "a" parameter were used to perform the final quantification. We collected 24 blood samples from normal and anemic populations. The adjusted R2 of the prediction results obtained from the multiple linear regression method reached 0.880, and the RMSE reached 9.04, which met the accuracy requirements of non-invasive detection of hemoglobin concentration.
Subject(s)
Biosensing Techniques , Smartphone , Humans , Biosensing Techniques/methods , Motion , Algorithms , HemoglobinsABSTRACT
The Mueller matrix contains abundant micro- and even nanostructural information of media. Especially, it can be used as a powerful tool to characterize anisotropic structures quantitatively, such as the particle size, density, and orientation information of fibers in the sample. Compared with unpolarized microscopic imaging techniques, Mueller matrix microscopy can also obtain some essential structural information about the sample from the derived parameters images at low resolution. Here, to analyze the comprehensive effects of imaging resolution on polarization properties obtained from the Mueller matrix, we, first, measure the microscopic Mueller matrices of unstained rat dorsal skin tissue slices rich in collagen fibers using a series of magnifications or numerical aperture (NA) values of objectives. Then, the first-order moments and image texture parameters are quantified and analyzed in conjunction with the polarization parameter images. The results show that the Mueller matrix polar decomposition parameters diattenuation D, linear retardance δ, and depolarization Δ images obtained using low NA objective retain most of the structural information of the sample and can provide fast imaging speed. In addition, the scattering phase function analysis and Monte Carlo simulation based on the cylindrical scatterers reveal that the diattenuation parameter D images with different imaging resolutions are expected to be used to distinguish among the fibrous scatterers in the medium with different particle sizes. This study provides a criterion to decide which structural information can be accurately and rapidly obtained using a transmission Mueller matrix microscope with low NA objectives to assist pathological diagnosis and other applications.
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Broad-spectrum resistance has great values for crop breeding. However, its mechanisms are largely unknown. Here, we report the cloning of a maize NLR gene, RppK, for resistance against southern corn rust (SCR) and its cognate Avr gene, AvrRppK, from Puccinia polysora (the causal pathogen of SCR). The AvrRppK gene has no sequence variation in all examined isolates. It has high expression level during infection and can suppress pattern-triggered immunity (PTI). Further, the introgression of RppK into maize inbred lines and hybrids enhances resistance against multiple isolates of P. polysora, thereby increasing yield in the presence of SCR. Together, we show that RppK is involved in resistance against multiple P. polysora isolates and it can recognize AvrRppK, which is broadly distributed and conserved in P. polysora isolates.
Subject(s)
Basidiomycota , Zea mays , Basidiomycota/genetics , Chromosome Mapping , Cloning, Molecular , Disease Resistance/genetics , Plant Breeding , Plant Diseases/genetics , Puccinia , Zea mays/geneticsABSTRACT
Time-division framework is commonly used in Mueller matrix polarimeters (MPs), which takes extra numbers of images at the same position in an acquisition sequence. In this Letter, we utilize measurement redundancy to raise a unique loss function which can reflect and evaluate the degree of mis-registration of Mueller matrix (MM) polarimetric images. Further, we demonstrate that the constant-step rotating MPs have a self-registration loss function free from systematic errors. Based on this property, we propose a self-registration framework, which is able to apply efficient sub-pixel registration skipping the calibration procedure of MPs. It is demonstrated that the self-registration framework performs well for tissue MM images. By combining with other powerful vectorized super-resolution methods, the framework proposed in this Letter has the potential to handle more complicated registration problems.
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Statistical Parametric Mapping (SPM) is a computational approach for analysing functional brain images like Positron Emission Tomography (PET). When performing SPM analysis for different patient populations, brain PET template images representing population-specific brain morphometry and metabolism features are helpful. However, most currently available brain PET templates were constructed using the Caucasian data. To enrich the family of publicly available brain PET templates, we created Chinese-specific template images based on 116 [18F]-fluorodeoxyglucose ([18F]-FDG) PET images of normal participants. These images were warped into a common averaged space, in which the mean and standard deviation templates were both computed. We also developed the SPM analysis programmes to facilitate easy use of the templates. Our templates were validated through the SPM analysis of Alzheimer's and Parkinson's patient images. The resultant SPM t-maps accurately depicted the disease-related brain regions with abnormal [18F]-FDG uptake, proving the templates' effectiveness in brain function impairment analysis.
Subject(s)
Brain Mapping , Brain , Positron-Emission Tomography , Asian People , Brain/diagnostic imaging , Brain/metabolism , China , Fluorodeoxyglucose F18 , HumansABSTRACT
Predicting the functional or pathogenic regulatory variants in the human non-coding genome facilitates the interpretation of disease causation. While numerous prediction methods are available, their performance is inconsistent or restricted to specific tasks, which raises the demand of developing comprehensive integration for those methods. Here, we compile whole genome base-wise aggregations, regBase, that incorporate largest prediction scores. Building on different assumptions of causality, we train three composite models to score functional, pathogenic and cancer driver non-coding regulatory variants respectively. We demonstrate the superior and stable performance of our models using independent benchmarks and show great success to fine-map causal regulatory variants on specific locus or at base-wise resolution. We believe that regBase database together with three composite models will be useful in different areas of human genetic studies, such as annotation-based casual variant fine-mapping, pathogenic variant discovery as well as cancer driver mutation identification. regBase is freely available at https://github.com/mulinlab/regBase.
Subject(s)
Databases, Genetic , Genome, Human , Genome-Wide Association Study/methods , Software , Datasets as Topic , Humans , Neoplasms/genetics , Polymorphism, Single Nucleotide/geneticsABSTRACT
This study aimed to compare the long-term outcomes of laparoscopic and open distal gastrectomy for advanced gastric cancer. Between January 2007 and December 2014, patients with advanced gastric cancer underwent distal gastrectomy by laparoscopic or open approach were identified. Patients in both groups were selected after being matched by age, gender, American Society of Anesthesiologists (ASA) class and clinical TNM stage using propensity score method, to create two comparable groups: laparoscopy and open groups, and prognosis were compared between these two groups. After the patients were matched, 86 patients in each group were selected for analysis. There were no significant differences in the clinicopathological features between the two groups. There were significant differences between the laparoscopy and open groups in terms of blood loss, duration of surgery, and hospital stay. The 5-year overall survival rate was 59% in laparoscopy group, and 56% in open group (P=0.523). The 5-year disease-free survival rate was 52% and 46%, respectively (P=0.362). According to the univariate and multivariate analysis, this type of surgical approach was not a prognostic factor for long-term outcomes. The current results indicated that laparoscopic distal gastrectomy is associated with similar overall survival and disease-free survival for advanced gastric cancer.
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Circulating tumor cells (CTCs), which have stem cell-like characteristics, might play a crucial role in cancer metastasis. CD44 has been identified as gastric cancer (GC) stem cell (CSC) marker. Here, the prognostic significance of CD44-positive CTCs in GC patients was investigated. CTCs were detected in 27 of 45 GC patients. The presence of CTCs was significantly associated with lymph node metastasis, distant metastasis, and recurrence (P = 0.007, P = 0.035, and P = 0.035, resp.). Nineteen of the 27 CTC-positive patients had CD44-positive CTCs. These patients were more likely to develop metastasis and recurrence than patients with CD44-negative CTCs. CD44-positive CTC counts were higher in recurrent patients than in the nonrecurrent ones (means 4.8 and 1.9, resp.; P = 0.010). Furthermore, 13 of 19 patients with CD44-positive CTCs developed recurrent disease, and the mean time to recurrence was shorter than that in patients with CD44-negative CTCs (10.54 ± 5.55 and 19.13 ± 9.72 months, resp.; P = 0.04). COX proportional hazards model indicated that the presence of CD44-positive CTCs and TNM stage were independent predictors of recurrence for GC (P = 0.030 and 0.008). So identifying the stem cell-like CTC subset may provide more clinically useful prognostic information than only detecting CTCs.