Structural Ni0-Niδ+ Pair Sites for Highly Active Hydrogenation of Nitriles to Primary Amines.

Supported metal pair sites have sparked interest due to their tremendous potential as bifunctional catalysts. Here, we report the structural Ni0-Niδ+ pair sites constructed in a well-defined nanocrystal phase of Ni3P. These Ni0-Niδ+ pair sites exhibited a remarkable product formation rate of 123 molBA/molmetal/h for the hydrogenation of benzonitrile (BN) to benzylamine (BA). The heterogeneity of surface Ni atoms over the Ni3P crystal created two types of metal centers, Ni0 and Niδ+, with a specific spatial distance of 4-5 Å. The Ni0 site acted as the center for H2 activation, while the Niδ+ site served as the adsorption and activation center for the C ≡ N group. The highly efficient cooperation effect of Ni0-Niδ+ pair sites resulted in a TOF of 2915 h-1 in BN hydrogenation, which is 2.4 and 9.7 times higher than that over the mono-Ni0 and -Niδ+ sites, respectively.

Interaction between Single Metal Atoms and UiO-66 Framework Revealed by Low-Dose Imaging.

Atomically dispersed metals encapsulated in metal-organic frameworks (MOFs) have attracted extensive attention in catalysis and energy fields. Amino groups were considered conducive to the formation of single atom catalysts (SACs) due to the strong metal-linker interactions. Here, atomic details of Pt1@UiO-66 and Pd1@UiO-66-NH2 are revealed using low-dose integrated differential phase contrast scanning transmission electron microscopy (iDPC-STEM). Single Pt atoms locate on the benzene ring of p-benzenedicarboxylic acid (BDC) linkers in Pt@UiO-66, while single Pd atoms are adsorbed by the amino groups in Pd@UiO-66-NH2. However, Pt@UiO-66-NH2 and Pd@UiO-66 show obvious clusters. Therefore, amino groups do not always favor the formation of SACs, and density functional theory (DFT) calculations indicate that a moderate binding strength between metals and MOFs is preferred. These results directly reveal the adsorption sites of single metal atoms in UiO-66 family, paving the way for understanding the interaction between single metal atoms and the MOFs.

Analysis and optimization of aberration induced by oblique incidence for in-vivo tissue polarimetry.

For in-vivo polarimetry such as Mueller matrix endoscopy of human internal organ cavities, the complicated undulating tissue surfaces deliver an inescapable occurrence of oblique incidence, which induce a prominent aberration to backscattering tissue polarimetry. In this Letter, we quantitatively analyze such polarimetric aberration on polarization basic parameters derived from the Mueller matrix. A correlation heatmap is obtained as applicable criteria to select an appropriate incident angle for different polarization basic parameters. Based on the analyzing results, we propose two aberration optimization strategies of parameter selection and azimuth rotation, which are suitable for tissue samples with randomly and well-aligned fiber textures, respectively. Both strategies are demonstrated to be effective in the ex-vivo human gastric muscularis tissue experiment. The findings presented in this Letter can be useful to provide accurate polarization imaging results, widely applied on in-vivo polarimetric endoscopy for tissues with complicated surface topography.

Self-registration of constant-step rotating Mueller matrix polarimeters.

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.

Reverse active learning based atrous DenseNet for pathological image classification.

BACKGROUND: Due to the recent advances in deep learning, this model attracted researchers who have applied it to medical image analysis. However, pathological image analysis based on deep learning networks faces a number of challenges, such as the high resolution (gigapixel) of pathological images and the lack of annotation capabilities. To address these challenges, we propose a training strategy called deep-reverse active learning (DRAL) and atrous DenseNet (ADN) for pathological image classification. The proposed DRAL can improve the classification accuracy of widely used deep learning networks such as VGG-16 and ResNet by removing mislabeled patches in the training set. As the size of a cancer area varies widely in pathological images, the proposed ADN integrates the atrous convolutions with the dense block for multiscale feature extraction. RESULTS: The proposed DRAL and ADN are evaluated using the following three pathological datasets: BACH, CCG, and UCSB. The experiment results demonstrate the excellent performance of the proposed DRAL + ADN framework, achieving patch-level average classification accuracies (ACA) of 94.10%, 92.05% and 97.63% on the BACH, CCG, and UCSB validation sets, respectively. CONCLUSIONS: The DRAL + ADN framework is a potential candidate for boosting the performance of deep learning models for partially mislabeled training datasets.

Breast Cancer Subtype Classification Using 4-Plex Droplet Digital PCR.

BACKGROUND: Infiltrating ductal carcinoma (IDCA) is the most common form of invasive breast cancer. Immunohistochemistry (IHC) is widely used to analyze estrogen receptor 1 (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) that can help classify the tumor to guide the medical treatment. IHC examinations require experienced pathologists to provide interpretations that are subjective, thereby lowering the reproducibility of IHC-based diagnosis. In this study, we developed a 4-plex droplet digital PCR (ddPCR) for the simultaneous and quantitative analyses of estrogen receptor 1 (ESR1), progesterone receptor (PGR), erb-b2 receptor tyrosine kinase 2 (ERBB2), and pumilio RNA binding family member 1 (PUM1) expression levels in formalin-fixed paraffin-embedded (FFPE) samples. METHODS: We evaluated the sensitivity, reproducibility, and linear dynamic range of 4-plex ddPCR. We applied this method to analyze 95 FFPE samples from patients with breast IDCA and assessed the agreement rates between ddPCR and IHC to evaluate its potential in classifying breast cancer subtypes. RESULTS: The limits of quantification (LOQ) were 25, 50, 50, and 50 copies per reaction for ERBB2, ESR1, PGR, and PUM1, respectively. The dynamic ranges of ESR1, PGR, and PUM1 extended over 50-1600 copies per reaction and those of ERBB2 from 25 to 1600 copies per reaction. The concordance correlation coefficients between 4-plex ddPCR and IHC were 96.8%, 91.5%, and 85.1% for ERBB2, ESR1, and PGR, respectively. Receiver operating characteristic curve area under the curve values of 0.991, 0.977, and 0.920 were generated for ERBB2, ESR1, and PGR, respectively. CONCLUSIONS: Evaluation of breast cancer biomarker status by 4-plex ddPCR was highly concordant with IHC in this study.

Identification and characterization of different tissues in blood vessel by multiplexed fluorescence lifetimes.

Herein, fluorescence lifetime imaging microscopy (FLIM) was used to directly measure eosin fluorescence lifetimes from H&E-stained umbilical artery, and a further utilization of eosin for high-content and multi-target analysis was proposed for the first time. Smooth muscles, collagens, and elastic fibers can be distinguished by eosin fluorescence lifetimes (P < 0.001). Erythrocytes, smooth muscles, elastic fibers, and type I and III collagen from the H&E-stained umbilical artery can be simultaneously identified by multiplexed fluorescence lifetimes of eosin. Use of eosin and lifetime-based separation is a potential method to simplify the special staining for clinicopathologic examination. Multiplexed eosin fluorescence lifetimes may be a newly developed method that can directly determine the relative content of elastic fiber and collagens from the H&E-stained sections. FLIM may have potential applications as an assisted tool in the assessment of the severity and complexity of cardiovascular diseases.

Enhanced Visualization of Hematoxylin and Eosin Stained Pathological Characteristics by Phasor Approach.

The phasor approach to fluorescence lifetime imaging microscopy (FLIM) is used to identify different types of tissues from hematoxylin and eosin (H&E) stained basal cell carcinoma (BCC) sections. The results suggest that working directly on the phasor space with the clustering assignment achieves immunofluorescence like simultaneous five or six-color imaging by using multiplexed fluorescence lifetimes of H&E. The phase approach is of particular effectiveness for enhanced visualization of the abnormal morphology of a suspected nidus. Moreover, the phasor approach to H&E FLIM data can determine the actual paths or the infiltrating trajectories of basophils and immune cells associated with the preneoplastic or neoplastic skin lesions. The integration of the phasor approach with routine histology proved its available value for skin cancer prevention and early detection. We therefore believe that the phasor analysis of H&E tissue sections is an enhanced visualization tool with the potential to simplify the preparation process of special staining and serve as color contrast aided imaging in clinical pathological examination.

Phasor-FLIM as a Screening Tool for the Differential Diagnosis of Actinic Keratosis, Bowen's Disease, and Basal Cell Carcinoma.

The aim of this study was to distinguish basal cell carcinoma (BCC) from actinic keratosis (AK) and Bowen's disease (BD) by fluorescence lifetimes of hematoxylin and eosin (H&E) and phasor analysis. Pseudocolor images of average fluorescence lifetime (τm) exhibited more contrast than conventional bright field and/or fluorescence images of H&E-stained sections. The mean values (µ) of τm distribution (τmµ) in three layers of skin were first explored for comparison with the corresponding layers of AK, BD, and BCC. Moreover, analysis of the H&E fluorescence lifetimes in the phasor space was performed by observing clusters in specific regions of the phasor plot. Various structures in the skin were distinguished. Comparisons of phase distributions from the corresponding layers of skin resulted in quantitative separation and calculation of distinctive parameters including coordinate values, diagonal slopes, and phasor areas. The combination of fluorescence lifetime imaging microscopy (FLIM) and phasor approach (phasor-FLIM) provides a simple method for histopathology analysis and can significantly improve the accuracy of bright field H&E diagnosis. We therefore believe that phasor-FLIM is an aided tool with the potential to provide rapid confirmation of diagnostic criteria and classification of histological types of skin neoplasms.

Nickel Cobaltite Nanostructures for Photoelectric and Catalytic Applications.

Bimetallic oxide nickel cobaltite (NiCo2 O4 ) shows extensive potential for innovative photoelectronic and energetic materials owing to their distinctive physical and chemical properties. In this review, representative fabrications and applications of NiCo2 O4 nanostructures are outlined for photoelectronic conversion, catalysis, and energy storage, aiming to promote the development of NiCo2 O4 nanomaterials in these fields through an analysis and comparison of their diverse nanostructures. Firstly, a brief introduction of the spinel structures, properties, and morphologies of NiCo2 O4 nanomaterials are presented. Then, the advanced progress of NiCo2 O4 nanomaterials for both photoelectronic conversion and energy fields is summarized including such examples as solar cells, electrocatalysis, and lithium ion batteries. Finally, further prospects and promising developments of NiCo2 O4 nanomaterials in these significant fields are proposed.

Automation-assisted cervical cancer screening in manual liquid-based cytology with hematoxylin and eosin staining.

Current automation-assisted technologies for screening cervical cancer mainly rely on automated liquid-based cytology slides with proprietary stain. This is not a cost-efficient approach to be utilized in developing countries. In this article, we propose the first automation-assisted system to screen cervical cancer in manual liquid-based cytology (MLBC) slides with hematoxylin and eosin (H&E) stain, which is inexpensive and more applicable in developing countries. This system consists of three main modules: image acquisition, cell segmentation, and cell classification. First, an autofocusing scheme is proposed to find the global maximum of the focus curve by iteratively comparing image qualities of specific locations. On the autofocused images, the multiway graph cut (GC) is performed globally on the a* channel enhanced image to obtain cytoplasm segmentation. The nuclei, especially abnormal nuclei, are robustly segmented by using GC adaptively and locally. Two concave-based approaches are integrated to split the touching nuclei. To classify the segmented cells, features are selected and preprocessed to improve the sensitivity, and contextual and cytoplasm information are introduced to improve the specificity. Experiments on 26 consecutive image stacks demonstrated that the dynamic autofocusing accuracy was 2.06 µm. On 21 cervical cell images with nonideal imaging condition and pathology, our segmentation method achieved a 93% accuracy for cytoplasm, and a 87.3% F-measure for nuclei, both outperformed state of the art works in terms of accuracy. Additional clinical trials showed that both the sensitivity (88.1%) and the specificity (100%) of our system are satisfyingly high. These results proved the feasibility of automation-assisted cervical cancer screening in MLBC slides with H&E stain, which is highly desirable in community health centers and small hospitals.

Electrosprayed hierarchical mesoporous Mn0.5Ti2(PO4)3@C microspheres as promising High-Performance anode for Potassium-Ion batteries.

NASICON-structured Ti-based polyanion compounds benefit from a stable structural framework, large ion channels, and fast ion mobility. However, the large radius of potassium and its poor electronic conductivity restrict its use in potassium-ion batteries. Herein, hierarchical mesoporous Mn0.5Ti2(PO4)3@C microspheres have been successfully synthesized using a simple electrospraying method. These microspheres consist of Mn0.5Ti2(PO4)3 nanoparticles evenly embedded in three-dimensional mesoporous carbon microspheres. The hierarchical mesoporous micro/nanostructure facilitates the rapid insertion and extraction of K+, while the three-dimensional carbon microspheres matrix enhances electrical conductivity and prevents active materials from collapsing during cycling. So the hierarchical mesoporous Mn0.5Ti2(PO4)3@C microspheres exhibit a high reversible discharge specific capacity (306 mA h g-1 at 20 mA g-1), a notable rate capability (123 mA h g-1 at 5000 mA g-1), and exceptional cycle performance (148 mA h g-1 at 500 mA g-1 after 1000 cycles). The results show that electrosprayed Mn0.5Ti2(PO4)3@C microspheres are a promising anode for PIBs.

The Detection of Circulating Antigen Glutathione S-Transferase in Sheep Infected with Fasciola hepatica with Double-Antibody Sandwich Signal Amplification Enzyme-Linked Immunosorbent Assay.

Fasciolosis is a global zoonotic parasitic disease caused by F. hepatica infection that is particularly harmful to cattle and sheep. A biotin-streptavidin signal amplification ELISA (streptavidin-ELISA/SA-ELISA) based on circulating antigens can allow for the early detection of F. hepatica-infected animals and is suitable for batch detection. It is considered to be a better means of detecting F. hepatica infection than traditional detection methods. In this study, using the serum of sheep artificially infected with F. hepatica, the cDNA expression library of F. hepatica was screened, 17 immunodominant antigen genes of F. hepatica were obtained, and glutathione s-transferase (GST) was selected as the candidate detection antigen. Firstly, the GST cDNA sequence was amplified from F. hepatica, followed by the preparation of recombinant protein GST (rFhGST). Then, monoclonal and polyclonal antibodies against rFhGST were prepared using the GST protein. Afterward, the immunolocalization of the target protein in the worm was observed via confocal microscopy, and it was found that the GST protein was localized in the uterus, intestinal tract, and body surface of F. hepatica. Finally, a double-antibody sandwich SA-ELISA based on the detection of circulating antigens was established. There was no cross-reaction with positive sera infected with Dicrocoelium lanceatum (D. lanceatum), Haemonchus contortus (H. contortus), Neospora caninum (N. caninum), or Schistosoma japonicum (S. japonicum). Forty serum and fecal samples from the same batch of sheep in Nong'an County, Changchun City, Jilin Province, China were analyzed using the established detection method and fecal detection method. The positive rate of the SA-ELISA was 17.5%, and the positive rate of the fecal detection method was 15%. The detection results of this method were 100% consistent with commercial ELISA kits. A total of 152 sheep serum samples were tested in Nong'an County, Changchun City, Jilin Province, and the positive rate was 5.92%. This study laid the foundation for the development of serological detection preparations for F. hepatica infection based on the detection of circulating antigens.

Analyzing the influence of oblique incidence on quantitative backscattering tissue polarimetry: a pilot ex vivo study.

Significance: Among the available polarimetric techniques, backscattering Mueller matrix (MM) polarimetry provides a promising non-contact and quantitative tool for in vivo tissue detection and clinical diagnosis. To eliminate the surface reflection from the sample cost-effectively, the non-collinear backscattering MM imaging setup always has an oblique incidence. Meanwhile, for practical organ cavities imaged using polarimetric gastrointestinal endoscopy, the uneven tissue surfaces can induce various relative oblique incidences inevitably, which can affect the polarimetry in a complicated manner and needs to be considered for detailed study. Aim: The purpose of this study is to systematically analyze the influence of oblique incidence on backscattering tissue polarimetry. Approach: We measured the MMs of experimental phantom and ex vivo tissues with different incident angles and adopted a Monte Carlo simulation program based on cylindrical scattering model for further verification and analysis. Meanwhile, the results were quantitatively evaluated using the Fourier transform, basic statistics, and frequency distribution histograms. Results: Oblique incidence can induce different changes on non-periodic, two-periodic, and four-periodic MM elements, leading to false-positive and false-negative polarization information for tissue polarimetry. Moreover, a prominent oblique incidence can bring more dramatic signal variations, such as phase retardance and element transposition. Conclusions: The findings presented in this study give some crucial criterions of appropriate incident angle selections for in vivo polarimetric endoscopy and other applications and can also be valuable references for studying how to minimize the influence further.

Imaging the dynamic influence of functional groups on metal-organic frameworks.

Metal-organic frameworks (MOFs) with different functional groups have wide applications, while the understanding of functionalization influences remains insufficient. Previous researches focused on the static changes in electronic structure or chemical environment, while it is unclear in the aspect of dynamic influence, especially in the direct imaging of dynamic changes after functionalization. Here we use integrated differential phase contrast scanning transmission electron microscopy (iDPC-STEM) to directly 'see' the rotation properties of benzene rings in the linkers of UiO-66, and observe the high correlation between local rigidity and the functional groups on the organic linkers. The rigidity is then correlated to the macroscopic properties of CO2 uptake, indicating that functionalization can change the capability through not only static electronic effects, but also dynamic rotation properties. To the best of our knowledge this is the first example of a technique to directly image the rotation properties of linkers in MOFs, which provides an approach to study the local flexibility and paves the way for potential applications in capturing, separation and molecular machine.

Comparative study of the influence of imaging resolution on linear retardance parameters derived from the Mueller matrix.

Polarization imaging techniques are emerging tools to provide quantitative information of anisotropic structures, such as the density and orientation distribution of fibers in tissue samples. Recently, it is found that when using Mueller matrix polarimetry to obtain the structural features of tissue samples, some information can be revealed by relatively low-resolution polarization parameter images. Thus, to analyze what kinds of anisotropic optical and structural information contained in high-resolution polarization images are preserved in low-resolution ones, here we carry out a comparative study of the influence of imaging resolution on the Mueller matrix derived linear retardance parameters. We measure the microscopic Mueller matrix of human healthy breast duct tissues and ductal carcinoma in situ (DCIS) tissues, which have distinct typical fibrous structures, using objectives with different numerical aperture. Then we quantitatively compare a group of image texture feature parameters of the linear retardance parameters images under high and low imaging resolutions. The results demonstrate that the fibers density information contained in the texture features of linear retardance δ parameter image are preserved well with the decline of imaging resolution. While for the azimuthal orientation parameter θ which closely related to the spatial location, we still need high imaging resolution to obtain quantitative structural information. The study provides an important criterion to decide which information of fibrous structures can be extracted accurately using transmission Mueller matrix microscope with low numerical aperture objectives.

Protective Immunity Against Neospora caninum Infection Induced by 14-3-3 Protein in Mice.

Neospora caninum is an apicomplexan parasite that infects many mammals and remains a threatening disease worldwide because of the lack of effective drugs and vaccines. Our previous studies demonstrated that N. caninum 14-3-3 protein (Nc14-3-3), which is included in N. caninum extracellular vesicles (NEVs), can induce effective immune responses and stimulate cytokine expression in mouse peritoneal macrophages. However, whether Nc14-3-3 has a protective effect and its mechanisms are poorly understood. Here, we evaluated the immune responses and protective effects of Nc14-3-3 against exposure to 2 × 107 Nc-1 tachyzoites. Antibody (IgG, IgGl, and IgG2a) levels and Th1-type (IFN-γ and IL-12) and Th2-type (IL-4 and IL-10) cytokines in mouse serum, survival rates, survival times, and parasite burdens were detected. In the present study, the immunostimulatory effect of Nc14-3-3 was confirmed, as it triggered Th1-type cytokine (IFN-γ and IL-12) production in mouse serum 2 weeks after the final immunization. Moreover, the immunization of C57BL/6 mice with Nc14-3-3 induced high IgG antibody levels and significant increases in CD8+ T lymphocytes in the spleens of mice, indicating that the cellular immune response was significantly stimulated. Mouse survival rates and times were significantly prolonged after immunization; the survival rates were 40% for Nc14-3-3 immunization and 60% for NEV immunization, while mice that received GST, PBS, or blank control all died at 13, 9, or 8 days, respectively, after intraperitoneal N. caninum challenge. In addition, qPCR analysis indicated that there was a reduced parasite burden and diminished pathological changes in the mice immunized with Nc14-3-3. Our data demonstrate that vaccination of mice with Nc14-3-3 elicits both cellular and humoral immune responses and provides partial protection against acute neosporosis. Thus, Nc14-3-3 could be an effective antigen candidate for vaccine development for neosporosis.

Deriving Polarimetry Feature Parameters to Characterize Microstructural Features in Histological Sections of Breast Tissues.

OBJECTIVE: Mueller matrix polarimetry technique has been regarded as a powerful tool for probing the microstructural information of tissues. The multiplying of cells and remodeling of collagen fibers in breast carcinoma tissues have been reported to be related to patient survival and prognosis, and they give rise to observable patterns in hematoxylin and eosin (H&E) sections of typical breast tissues (TBTs) that the pathologist can label as three distinctive pathological features (DPFs)-cell nuclei, aligned collagen, and disorganized collagen. The aim of this paper is to propose a pixel-based extraction approach of polarimetry feature parameters (PFPs) using a linear discriminant analysis (LDA) classifier. These parameters provide quantitative characterization of the three DPFs in four types of TBTs. METHODS: The LDA-based training method learns to find the most simplified linear combination from polarimetry basis parameters (PBPs) constrained under the accuracy remains constant to characterize the specific microstructural feature quantitatively in TBTs. RESULTS: We present results from a cohort of 32 clinical patients with analysis of 224 regions-of-interest. The characterization accuracy for PFPs ranges from 0.82 to 0.91. CONCLUSION: This work demonstrates the ability of PFPs to quantitatively characterize the DPFs in the H&E pathological sections of TBTs. SIGNIFICANCE: This technique paves the way for automatic and quantitative evaluation of specific microstructural features in histopathological digitalization and computer-aided diagnosis.

Probing variations of fibrous structures during the development of breast ductal carcinoma tissues via Mueller matrix imaging.

Recently, we developed a label-free method to probe the microstructural information and optical properties of unstained thin tissue slices based on microscopic Mueller matrix imaging technique. In this paper, we take the microscopic Mueller matrix images of human breast ductal carcinoma tissue samples at different pathological stages, and then calculate and analyze their retardance-related Mueller matrix-derived parameters. To reveal the microstructural features more quantitatively and precisely, we propose a new method based on first-order statistical properties of image to transform the 2D images of Mueller matrix parameters into several statistical feature vectors. We evaluate each statistical feature vector by corresponding classification characteristic value extracted from the statistical features of Mueller matrix parameters images of healthy breast duct tissue samples. The experimental results indicate that these statistical feature vectors of Mueller matrix derived parameters may become powerful tools to quantitatively characterize breast ductal carcinoma tissue samples at different pathological stages. It has the potential to facilitate automating the staging process of breast ductal carcinoma tissue, resulting in the improvement of diagnostic efficiency.