NuSEA: Nuclei Segmentation With Ellipse Annotations.

OBJECTIVE: Nuclei segmentation is a crucial pre-task for pathological microenvironment quantification. However, the acquisition of manually precise nuclei annotations for improving the performance of deep learning models is time-consuming and expensive. METHODS: In this paper, an efficient nuclear annotation tool called NuSEA is proposed to achieve accurate nucleus segmentation, where a simple but effective ellipse annotation is applied. Specifically, the core network U-Light of NuSEA is lightweight with only 0.86 M parameters, which is suitable for real-time nuclei segmentation. In addition, an Elliptical Field Loss and a Texture Loss are proposed to enhance the edge segmentation and constrain the smoothness simultaneously. RESULTS: Extensive experiments on three public datasets (MoNuSeg, CPM-17, and CoNSeP) demonstrate that NuSEA is superior to the state-of-the-art (SOTA) methods and better than existing algorithms based on point, rectangle, and text annotations. CONCLUSIONS: With the assistance of NuSEA, a new dataset called NuSEA-dataset v1.0, encompassing 118,857 annotated nuclei from the whole-slide images of 12 organs is released. The codes and the new dataset are publicly available at https://github.com/dreambamboo/NuSEA/. SIGNIFICANCE: NuSEA provides a rapid and effective annotation tool for nuclei in histopathological images, benefiting future explorations in deep learning algorithms.

MTCSNet: One-stage learning and two-point labeling are sufficient for cell segmentation.

Deep convolution neural networks have been widely used in medical image analysis, such as lesion identification in whole-slide images, cancer detection, and cell segmentation, etc. However, it is often inevitable that researchers try their best to refine annotations so as to enhance the model performance, especially for cell segmentation task. Weakly supervised learning can greatly reduce the workload of annotations, while there is still a huge performance gap between the weakly and fully supervised learning approaches. In this work, we propose a weakly-supervised cell segmentation method, namely Multi-Task Cell Segmentation Network (MTCSNet), for multi-modal medical images, including pathological, brightfield, fluorescent, phase-contrast and differential interference contrast images. MTCSNet is learnt in a single-stage training manner, where only two annotated points for each cell provide supervision information, and the first one is the centroid, the second one is its boundary. Additionally, five auxiliary tasks are elaborately designed to train the network, including two pixel-level classifications, a pixel-level regression, a local temperature scaling and an instance-level distance regression task, which is proposed to regress the distances between the cell centroid and its boundaries in eight orientations. The experimental results indicate that our method outperforms all state-of-the-art weakly-supervised cell segmentation approaches on public multi-modal medical image datasets. The promising performance also shows that a single-stage learning with two-point labeling approach are sufficient for cell segmentation, instead of fine contour delineation. The codes are available at: https://github.com/binging512/MTCSNet.

A Potential "Anti-Warburg Effect" in Circulating Tumor Cell-mediated Metastatic Progression?

Metabolic reprogramming is a defining hallmark of cancer metastasis, warranting thorough exploration. The tumor-promoting function of the "Warburg Effect", marked by escalated glycolysis and restrained mitochondrial activity, is widely acknowledged. Yet, the functional significance of mitochondria-mediated oxidative phosphorylation (OXPHOS) during metastasis remains controversial. Circulating tumor cells (CTCs) are considered metastatic precursors that detach from primary or secondary sites and harbor the potential to seed distant metastases through hematogenous dissemination. A comprehensive metabolic characterization of CTCs faces formidable obstacles, including the isolation of these rare cells from billions of blood cells, coupled with the complexities of ex vivo-culturing of CTC lines or the establishment of CTC-derived xenograft models (CDX). This review summarized the role of the "Warburg Effect" in both tumorigenesis and CTC-mediated metastasis. Intriguingly, bioinformatic analysis of single-CTC transcriptomic studies unveils a potential OXPHOS dominance over Glycolysis signature genes across several important cancer types. From these observations, we postulate a potential "Anti-Warburg Effect" (AWE) in CTCs-a metabolic shift bridging primary tumors and metastases. The observed AWE could be clinically important as they are significantly correlated with therapeutic response in melanoma and prostate patients. Thus, unraveling dynamic metabolic regulations within CTC populations might reveal an additional layer of regulatory complexities of cancer metastasis, providing an avenue for innovative anti-metastasis therapies.

Ganoderma lucidum polysaccharides ameliorates D-galactose-induced aging salivary secretion disorders by upregulating the rhythm and aquaporins.

Longer-term deterioration in saliva secretion has been observed to occur in response to aging. The functional deterioration of the salivary gland damages swallowing and chewing abilities and consequently reduces life quality of the elderly. There are, however, only a few proven effective treatments for aging salivary secretion disorders. Ganoderma lucidum polysaccharide (GLP) has been applied to treat various diseases because of its safety, efficacy, and low cost. We investigated the protective effect of GLP on the submandibular gland (SMG) during aging. D-galactose (D-gal) was used to treat the aging mice, and the body weight, water consumption, saliva secretion, and flow rate were measured after 6 weeks of modeling. Micromorphological changes of the SMG were assessed by hematoxylin-eosin staining and transmission electron microscopy. RT-qPCR and Western blot were used to detect the expression of apoptotic proteins and inflammatory cytokines. Aquaporins (AQPs) and rhythmic protein expression were analyzed by immunohistochemistry and immunofluorescence. The results showed that GLP effectively promoted the expression of AQP5, AQP4, and AQP1, inhibited the release of TNF-α, IL-6, and Bax, and reduced inflammation and apoptosis. Further experiments showed that GLP promoted the up-regulation of core clock genes and proteins and restored the co-localized expression of CLOCK and AQP5 that were weakened during aging, helping to attenuate aging-induced weight loss, decreased salivation, and structural and functional damage. The findings of this work contribute to understanding the nature of age-related modifications in SMG by identifying changes in AQP5 expression and regulatory mechanisms linked to SMG dysfunction during aging. GLP is a potential drug for maintaining healthy salivary gland (SG) status and preventing SG deficiency in the elderly.

Three cases of hepatic epithelioid hemangioendothelioma evaluated using conventional and contrast-enhanced ultrasound: Case reports.

Hepatic epithelioid hemangioendothelioma (HEHE) is a very rare vascular endothelial cell tumor, which lacks typical clinical manifestations and specificity of imaging features. Whether the background of fatty liver and the difference in Contrast enhanced ultrasound (CEUS) characteristics between large and small lesions has not been well defined. In this case reports, we described the ultrasound image features of three patients with HEHE. These three patients with HEHE have certain similar characteristics of conventional ultrasound and CEUS. CEUS imaging features include large nodules show earlier perfusion than liver parenchyma, with rim-enhancement, nonenhancing regions in the center, while small nodules show earlier perfusion than liver parenchyma, with hyperenhancement. All nodules show faster washout than hepatic parenchyma, showing heterogeneous hypoenhancement, and more washout lesions can be found in the PVP and LP. Conventional ultrasound and CEUS not only help to improve the diagnostic confidence of HEHE of rare liver tumors, but also can guide the biopsy area, making it easier to make accurate pathological diagnosis.

Enhancing Hydrogen Evolution by Optimizing the Hydrogen Adsorption on Titanium Monoxide Nanodot-Decorated Cobalt Sulfide Nanosheets.

Modulating the local electronic state of metal compounds through interfacial interaction has become a key method for manufacturing high-performance hydrogen evolution reaction (HER) electrocatalysts. The electron-rich active sites can promote the adsorption of hydrogen, which accelerates the Volmer step and thereby enhances the electrocatalytic performance of HER. Here, we found that the strong interfacial interaction between TiO nanodots (TiO/Co-S) and Co-S nanosheets could advantageously improve the performance toward HER of electrocatalyst. Meanwhile, XPS results showed that modulating the local electronic structure of the TiO nanodots produces electron-rich regions on Co. As a result, the overpotential of the TiO/Co-S nanocomposite at 10 mA cm-2 was 107 mV, and the Tafel slope was 83.3 mV dec-1 . This study focused on the effect of the solid-solid interface on the local electronic structure of the catalytic metal active sites and successfully improved the catalytic activity of transition metal materials in HER catalysis.

Correlation Analysis of Conventional Ultrasound Characteristics and Strain Elastography with Ki-67 Status in Breast Cancer.

Our objectives were to measure the relationships between conventional ultrasound features, strain elastography in breast cancer and Ki-67 index and to identify parameters that predict Ki-67 index. We included 181 lesions of 178 patients who underwent surgery for breast cancer at Xianyang Central Hospital. In multivariate logistic regression analysis, strain elastography and axillary-node metastasis showed significant Ki-67 index values; the overall theoretical prediction percentage correct was 75.7%. Strain elastography showed that the median Ki-67 index in the hard group was higher than that in the soft group, and the Ki-67 index increased with increasing elasticity score. This finding may guide ultrasound-guided breast tumor biopsy for selection of puncture regions. The combined use of the Ki-67 index for strain-elastography prediction and puncture-biopsy pathology reports may increase the accuracy of clinical treatment.

Effect of Health Education Based on Behavioral Change Theories on Self-Efficacy and Self-Management Behaviors in Patients with Chronic Heart Failure.

BACKGROUND: We aimed to explore the effect of health education and nursing intervention model based on behavioral change theories on self-efficacy and self-management behaviors in patients with chronic heart failure. METHODS: Eighty-six patients with chronic heart failure treated in the First Hospital Affiliated to Harbin Medical University (Harbin, China) from November 2016 to January 2018 were enrolled in this study. The patients were evenly divided into control group and observation group (43 patients in each group), according to the random number table method. Patients in the control group received a routine health education intervention. Patients in the observation group received health education based on behavioral change theories in addition to the routine nursing intervention. The health education included mastering of the disease-related theoretical knowledge, daily self-management and exercising guidance. After 8 weeks of intervention, the self-efficacy level, self-management ability and quality of life were assessed and compared between the two groups. RESULTS: The self-management behavior score in the observation group was higher than those in the control group (P=0.002). The chronic disease general self-efficacy (GSE) score in the observation group was higher than those in the control group (P=0.002). The quality of life (MHL) score was in the observation group was higher than those in the control group. The patient satisfaction score in the observation group was higher than those in the control group (P=0.021). CONCLUSION: Health education based on behavioral change theories can relieve symptoms of chronic heart failure, and improve patients' self-efficacy level, self-management ability and patient satisfaction.

New potassium-sodium niobate material system: a giant-d33 and high-T(C) lead-free piezoelectric.

In this work, we elucidate the influence of Bi(0.5)Li(0.5)ZrO3 (BLZ) content on the phase structure, microstructure, and electrical properties of (1 -x)K(0.40)Na(0.60)Nb(0.965)Sb(0.035)O3-xBi(0.5)Li(0.5)ZrO3 lead-free ceramics. We simultaneously achieved a giant d33 and a high T(C) in this material system. The coexistence of rhombohedral and tetragonal phases is responsible for such a large d33 in the ceramics with BLZ contents (x) ranging from 0.025 to 0.035. Doping with BLZ not only induces the formation of the phase boundary, but also maintains a high T(C). The ceramic with x = 0.03 shows an enhanced piezoelectric behaviour (d33 ~ 400 pC N(-1) and k(p) ~ 0.47) together with a high T(C) of 292 °C. A good temperature stability for ferroelectricity and piezoelectricity is also observed in these ceramics. This study is the first time that such a good comprehensive performance has been obtained in potassium-sodium niobate materials. We believe that this type of material system possessing giant-d33 and high-T(C) is a promising candidate for use in high-temperature piezoelectric devices.

Wide phase boundary zone, piezoelectric properties, and stability in 0.97(K0.4Na0.6)(Nb1-xSbx)O3-0.03Bi0.5Li0.5ZrO3 lead-free ceramics.

In this work, the rhombohedral (R) and tetragonal (T) phase boundary of the 0.97(K0.4Na0.6)(Nb1-xSbx)O3-0.03Bi0.5Li0.5ZrO3 piezoceramics has been attained in a wide composition range of 0.035 ≤ x ≤ 0.08, and the Sb(5+) could simultaneously shrink its TR-O and TO-T. A giant d33 of 380-405 pC N(-1) and a TC of 200-292 °C have been observed in the ceramics with the coexistence of both R and T phases. In addition, the ceramics with 0.035 ≤ x ≤ 0.08 also show a good thermal stability of the d33, and an enhanced temperature stability of ferroelectricity could be observed in the ceramic with x = 0.035. As a result, adding the optimum antimony content is an efficient way to promote the electrical properties of potassium-sodium niobate ceramics with the R-T phase boundary.

New potassium-sodium niobate ceramics with a giant d33.

For potassium-sodium niobate, poor piezoelectric properties always perplex most researchers, and then it becomes important to attain a giant piezoelectricity. Here we reported a giant piezoelectric constant in (1-x)(K0.48Na0.52)(Nb0.95Sb0.05)O3-xBi0.5Ag0.5ZrO3 lead-free ceramics. The rhombohedral-tetragonal phase boundary was shown in the ceramics with 0.04

Giant piezoelectricity in potassium-sodium niobate lead-free ceramics.

Environment protection and human health concern is the driving force to eliminate the lead from commercial piezoelectric materials. In 2004, Saito et al. [ Saito et al., Nature , 2004 , 432 , 84 . ] developed an alkali niobate-based perovskite solid solution with a peak piezoelectric constant d33 of 416 pC/N when prepared in the textured polycrystalline form, intriguing the enthusiasm of developing high-performance lead-free piezoceramics. Although much attention has been paid on the alkali niobate-based system in the past ten years, no significant breakthrough in its d33 has yet been attained. Here, we report an alkali niobate-based lead-free piezoceramic with the largest d33 of ∼490 pC/N ever reported so far using conventional solid-state method. In addition, this material system also exhibits excellent integrated performance with d33∼390-490 pC/N and TC∼217-304 °C by optimizing the compositions. This giant d33 of the alkali niobate-based lead-free piezoceramics is ascribed to not only the construction of a new rhombohedral-tetragonal phase boundary but also enhanced dielectric and ferroelectric properties. Our finding may pave the way for "lead-free at last".

New lead-free piezoelectric ceramics based on (K0.48Na0.52)(Nb0.95Ta0.05)O3-Bi0.5(Na0.7K0.2Li0.1)0.5ZrO3.

(1 - x)(K0.48Na0.52)(Nb0.95Ta0.05)O3-xBi0.5(Na0.7K0.2Li0.1)0.5ZrO3 lead-free piezoelectric ceramics with a new type of phase boundary have been designed and fabricated. This phase boundary lies in the compositional range of 0.04 ≤ x ≤ 0.05, and is formed by the coexistence of the rhombohedral, orthorhombic, and tetragonal phases. Interestingly, we found that the ferroelectric, dielectric, and piezoelectric properties of the ceramics with compositions near the phase boundary are significantly enhanced. In particular, the ceramic with x = 0.045 shows the best piezoelectric behavior of d33 ∼ 290 pC/N and kp ∼ 0.42 among all the compositions studied in this work, and it also exhibits a good thermal stability at annealing temperatures of ≤270 °C. All these results indicate that such a material system is a good candidate for lead-free piezoelectric applications in the future.

Mediating the contradiction of d33 and TC in potassium-sodium niobate lead-free piezoceramics.

For potassium-sodium niobate, the piezoelectric constant (d33) was usually improved by sacrificing the Curie temperature (TC). In this work, a material system of 0.992(K0.46Na0.54)0.965Li0.035Nb(1-x)Sb(x)O3-0.008BiScO3 has been designed and prepared with the aim of achieving both a large d33 and a high TC at the same time. The chemical compositions are found to be homogeneously distributed in the ceramics. The introduction of Sc is found to be responsible for different grain sizes. The rhombohedral-tetragonal phase coexistence zone lies in the composition range of 0.02

Lead-free piezoelectrics based on potassium-sodium niobate with giant d(33).

High-performance lead-free piezoelectrics (d33 > 400 pC/N) based on 0.96(K0.5Na0.5)0.95Li0.05Nb1-xSbxO3-0.04BaZrO3 with the rhombohedral-tetragonal (R-T) phase boundary have been designed and prepared. The R-T phase boundary lies the composition range of 0.04 ≤ x ≤ 0.07, and the dielectric and piezoelectric properties of the ceramics with the compositions near the phase boundary are significantly enhanced. In addition, the ceramic with x = 0.07 has a giant d33 of ~425 pC/N, which is comparable to that (~416 pC/N) of textured KNN-based ceramics (Saito, Y.; Takao, H.; Tani, T.; Nonoyama, T.; Takatori, K.; Homma, T.; Nagaya, T.; Nakamura, M. Nature 2004, 432, 84). The underlying physical mechanisms for enhanced piezoelectric properties are addressed. We believe that the material system is the most promising lead-free piezoelectric candidates for the practical applications.