Investigation of correlation between shear wave elastography and lymphangiogenesis in invasive breast cancer and diagnosis of axillary lymph node metastasis.

BACKGROUND: Accurate evaluation of axillary lymph node metastasis (LNM) in breast cancer is very important. A large number of hyperplastic and dilated lymphangiogenesis cases can usually be found in the pericancerous tissue of breast cancer to promote the occurrence of tumor metastasis.Shear wave elastography (SWE) can be used as an important means for evaluating pericancerous stiffness. We determined the stiffness of the pericancerous by SWE to diagnose LNM and lymphangiogenesis in invasive breast cancer (IBC). METHODS: Patients with clinical T1-T2 stage IBC who received surgical treatment in our hospital from June 2020 to December 2020 were retrospectively enrolled. A total of 299 patients were eventually included in the preliminary study, which included an investigation of clinicopathological features, ultrasonic characteristics, and SWE parameters. Multivariable logistic regression analysis was used to establish diagnostic model and evaluated its diagnostic performance of LNM. The correlation among SWE values, collagen volume fraction (CVF), and microlymphatic density (MLD) in primary breast cancer lesions was analyzed in another 97 patients. RESULTS: The logistic regression model is Logit(P)=-1.878 + 0.992*LVI-2.010*posterior feature enhancement + 1.230*posterior feature shadowing + 0.102*posterior feature combined pattern + 0.009*Emax. The optimum cutoff value of the logistic regression model was 0.365, and the AUC (95% CI) was 0.697 (0.636-0.758); the sensitivity (70.7 vs. 54.3), positive predictive value (PPV) (54.0 vs. 50.8), negative predictive value (NPV) (76.9 vs. 69.7), and accuracy (65.2 vs. 61.9) were all higher than Emax. There was no correlation between the SWE parameters and MLD in primary breast cancer lesions. CONCLUSIONS: The logistic regression model can help us to determine LNM, thus providing more imaging basis for the selection of preoperative treatment. The SWE parameter of the primary breast cancer lesion cannot reflect the peritumoral lymphangiogenesis, and we still need to find a new ultrasonic imaging method.

Extremal quantum correlation generation using a hybrid channel.

The preservation of quantum correlations requires optimal procedures and the proper design of the transmitting channels. In this regard, we address designing a hybrid channel comprising a single-mode cavity accompanied by a super-Gaussian beam and local dephasing parts based on the dynamics of quantum characteristics. We choose two-level atoms and various functions such as traced-distance discord, concurrence, and local-quantum uncertainty to analyze the effectiveness of the hybrid channel to preserve quantum correlations along with entropy suppression discussed using linear entropy. The joint configuration of the considered fields is found to not only preserve but also generate quantum correlations even in the presence of local dephasing. Most importantly, within certain limits, the proposed channel can be readily regulated to generate maximal quantum correlations and complete suppression of the disorder. Besides, compared to the individual parts, mixing the Fock state cavity, super-Gaussian beam, and local dephasing remains a resourceful choice for the prolonged quantum correlations' preservation. Finally, we present an interrelationship between the considered two-qubit correlations' functions, showing the deviation between each two correlations and of the considered state from maximal entanglement under the influence of the assumed hybrid channel.

[Activation of Hippo Pathway Proteins in Thrombin-Stimulated Platelets and Regutates Platelets Activation in Vitro].

OBJECTIVE: To investigate the phosphorylation levels of Hippo pathway proteins in thrombin stimulated platelets and to explore its effects on platelet activation. METHODS: The phosphorylation levels of Hippo pathway proteins - Mammalian STE20-like kinase 1/2 (MST1/2), Nuclear Dbf2 related kinase 1/2 (NDR1/2) and Mps one binder 1(MOB1) in human thrombin stimulated platelets was detected by Western blot. The effect of MST1/2 inhibitor XMU-MP-1 on platelet aggregation was detected by Platelet Aggregometer. The effect of XMU-MP-1 on platelet integrin αIIbß3 activation and CD62p expression was detected by flow cytometry. The effect of XMU-MP-1 on the "outside-in" signal of platelet integrin was detected by blood clot retraction test. The effects of XMU-MP-1 on platelet Hippo pathway proteins and p38 phosphorylation levels was detected by Western blot. RESULTS: The phosphorylation levels of MST1/2, NDR1/2 and MOB1 were significantly increased in thrombin activated platelets; XMU-MP-1 inhibited thrombin-induced platelet aggregation and αIIbß3 activation, but did not affect α-granules release and clot retraction. In addition, thrombin induced phosphorylation of the Hippo proteins were decreased in XMU-MP-1 treated platelets, while the phosphorylation of p38 was not affected. CONCLUSION: In thrombin stimulated platelets, Hippo pathway proteins were activated and contributed to platelets activation.

New insights into mechanisms of berberine in alleviating reproductive disorders of polycystic ovary syndrome: Anti-inflammatory properties.

Polycystic ovary syndrome (PCOS) is a complex reproductive disorder that seriously harms female reproductive health and decreases quality of life. Although spontaneous or assisted ovulation occurs, women with PCOS suffer from poor-quality oocytes and embryos and lower fertilization and final pregnancy rates. Therefore, it is urgent to identify new pathological mechanisms and discover the underlying therapeutic targets for reproductive disorders associated with PCOS. Berberine, one of the famous traditional Chinese medicines, has been shown to improve ovulation and live birth rates in women with PCOS. The effects of berberine on insulin resistance and abnormal glucose and lipid metabolism for restoring the reproductive health of women with PCOS are well recognized and have been widely studied, but much less attention has been given to its anti-inflammatory properties. Chronic low-grade inflammation is the unifying feature of PCOS and may contribute to reproductive disorders in PCOS. Berberine can modulate the inflammatory state of the ovaries and uterus in PCOS. The anti-inflammatory properties of berberine may provide new insight into the mechanisms by which berberine alleviates reproductive disorders associated with PCOS. Here, we summarized the most recent insights into the anti-inflammatory properties of berberine in PCOS reproductive disorders to inspire researchers to pursue new study directions involving berberine.

Single-cell characterization revealed hypoxia-induced metabolic reprogramming of gastric cancer.

Introduction: Gastric cancer (GC) is one of the most common malignant tumors worldwide. Single-cell sequencing technology can achieve an accurate and unbiased assessment of cell heterogeneity. Therefore, it is necessary to explore the molecular characteristics of GC-related malignant cells at a single-cell resolution. Methods: Single-cell RNA sequencing GC profiles were collected from the Gene Expression Omnibus database. Moreover, feature gene sets of metabolic pathways and hypoxia signals were collected from the Molecular Signatures Database. The marker genes of specific cell types were collected from the published literature and CellMarker database. The R package InferCNV was used to calculate the copy-number variations of cells and to identify real cancer cells. The weighted relative pathway activity algorithm was used to evaluate the differences in metabolic activity between cell types. Results: Our study found that cancer epithelial cells exhibited individual differences in molecular features and showed metabolic heterogeneity. Oxidative phosphorylation and glycolytic pathway activity were the major contributors to the metabolic heterogeneity of cancer epithelial cells. Furthermore, we used the hypoxia signaling pathway to indirectly evaluate the oxygen content of cells and found that hypoxia contributed to the heterogeneity of cancer epithelial cells. Finally, functional identification of genes co-expressed with HIF1A showed that the reprogramming of the oxidative stress response contributed to the tumor malignant progression. Conclusions: This study described hypoxia-induced metabolic reprogramming of GC at a single-cell level, partially addressing the lack of insight into the heterogeneity of cancer cell metabolism when using traditional sequencing technology.

Epigallocatechin-3-gallate reduces neutrophil extracellular trap formation and tissue injury in severe acute pancreatitis.

Neutrophil extracellular traps (NETs) promote intra-acinar trypsin activation and tissue damage. Therefore, reducing NET formation can reduce tissue damage in severe acute pancreatitis (SAP). However, NET formation pathways may differ among disease models. In this study, we evaluated the role of the myeloperoxidase-neutrophil elastase (NE) pathway in NET formation in SAP. SAP was induced by intraperitoneal injection of cerulein and LPSs in mice, and NE activity was inhibited by GW311616. Pancreatic tissues were collected for multiplex immunofluorescence, scanning electron microscopy, and western blotting to detect NET formation and the effect of NE on citrullinated histone H3, followed by analyses of serum amylase and cytokine levels. Pretreatment with GW311616 significantly reduced NET formation, pancreatic tissue damage, and systemic inflammatory responses in SAP. Network pharmacology analyses using NE as the target revealed the monomeric compound epigallocatechin-3-gallate (EGCG). Binding between EGCG and NE was validated using molecular docking, and the ability of EGCG to inhibit NE activity was verified experimentally. NET formation by PMA-stimulated neutrophils was significantly reduced in vitro when the cells were pretreated with 40 µM EGCG. Pretreatment with EGCG significantly reduced NET formation, pancreatic tissue damage, and systemic inflammatory responses in vivo. These results reveal that NET formation requires the myeloperoxidase-NE pathway, and citrullination of histone H3 is affected by NE activity in SAP. EGCG shows therapeutic potential for affecting NE activity, NET formation, and systemic inflammation in SAP.

Roles, detection, and visualization of neutrophil extracellular traps in acute pancreatitis.

Neutrophil extracellular traps (NETs) are produced in large quantities at the site of inflammation, and they locally capture and eliminate various pathogens. Thus, NETs quickly control the infection of pathogens in the body and play vital roles in immunity and antibacterial effects. However, evidence is accumulating that NET formation can exacerbate pancreatic tissue damage during acute pancreatitis (AP). In this review, we describe the research progress on NETs in AP and discuss the possibility of NETs as potential therapeutic targets. In addition, since the current detection and visualization methods of NET formation are not uniform and the selection of markers is still controversial, a synopsis of these issues is provided in this review.

Fuel source shift or cost reduction: Context-dependent adaptation strategies in closely related Neodon fuscus and Lasiopodomys brandtii against hypoxia.

Oxygen is essential for most life forms. Insufficient oxygen supply can disrupt homeostasis and compromise survival, and hypoxia-induced cardiovascular failure is fatal in many animals, including humans. However, certain species have adapted and evolved to cope with hypoxic environments and are therefore good models for studying the regulatory mechanisms underlying responses to hypoxia. Here, we explored the physiological and molecular responses of the cardiovascular system in two closely related hypoxia-adapted species with different life histories, namely, Qinghai voles ( Neodon fuscus) and Brandt's voles ( Lasiopodomys brandtii), under hypoxic (10% O 2 for 48 h) and normoxic (20.9% O 2 for 48 h) exposure. Kunming mice ( Mus musculus) were used for comparison. Qinghai voles live in plateau areas under hypoxic conditions, whereas Brandt's voles only experience periodic hypoxia. Histological and hematological analyses indicated a strong tolerance to hypoxia in both species, but significant cardiac tissue damage and increased blood circulation resistance in mice exposed to hypoxia. Comparative transcriptome analysis revealed enhanced oxygen transport efficiency as a coping mechanism against hypoxia in both N. fuscus and L. brandtii, but with some differences. Specifically, N. fuscus showed up-regulated expression of genes related to accelerated cardiac contraction and angiogenesis, whereas L. brandtii showed significant up-regulation of erythropoiesis-related genes. Synchronized up-regulation of hemoglobin synthesis-related genes was observed in both species. In addition, differences in cardiometabolic strategies against hypoxia were observed in the rodents. Notably, M. musculus relied on adenosine triphosphate (ATP) generation via fatty acid oxidation, whereas N. fuscus shifted energy production to glucose oxidation under hypoxic conditions and L. brandtii employed a conservative strategy involving down-regulation of fatty acid and glucose oxidation and a bradycardia phenotype. In conclusion, the cardiovascular systems of N. fuscus and L. brandtii have evolved different adaptation strategies to enhance oxygen transport capacity and conserve energy under hypoxia. Our findings suggest that the coping mechanisms underlying hypoxia tolerance in these closely related species are context dependent.

Advances in research on the effects of platelet activation in acute lung injury (Review).

Acute lung injury (ALI) is an acute hypoxic respiratory insufficiency or failure caused by various factors inside and outside the lungs. ALI is associated with high morbidity and a poor prognosis in hospitalized patients. The lungs serve as a reservoir for platelet precursor megakaryocytes and are closely associated with platelets. Platelets not only play a central role in hemostasis, coagulation and wound healing, but can also act as inflammatory cells capable of stimulating non-hemostatic immune functions under inflammatory conditions, participating in the progression of various inflammatory diseases, and can result in tissue damage. Therefore, it was speculated that platelets may play an important role in the pathogenesis of ALI. In this review, the latest research progress on secretion of bioactive mediators from platelets, platelet activation-related signaling pathways, and the direct contact reactions between platelets and neutrophils with endothelial cells that result in ALI are described, providing evidence to support the importance of the consideration of platelets in the search for ALI interventional targets.

Enhanced Identification of Novel Potential Variants for Appendicular Lean Mass by Leveraging Pleiotropy With Bone Mineral Density.

Strong relationships have been found between appendicular lean mass (ALM) and bone mineral density (BMD). It may be due to a shared genetic basis, termed pleiotropy. By leveraging the pleiotropy with BMD, the aim of this study was to detect more potential genetic variants for ALM. Using the conditional false discovery rate (cFDR) methodology, a combined analysis of the summary statistics of two large independent genome wide association studies (GWAS) of ALM (n = 73,420) and BMD (n = 10,414) was conducted. Strong pleiotropic enrichment and 26 novel potential pleiotropic SNPs were found for ALM and BMD. We identified 156 SNPs for ALM (cFDR <0.05), of which 74 were replicates of previous GWASs and 82 were novel SNPs potentially-associated with ALM. Eleven genes annotated by 31 novel SNPs (13 pleiotropic and 18 ALM specific) were partially validated in a gene expression assay. Functional enrichment analysis indicated that genes corresponding to the novel potential SNPs were enriched in GO terms and/or KEGG pathways that played important roles in muscle development and/or BMD metabolism (adjP <0.05). In protein-protein interaction analysis, rich interactions were demonstrated among the proteins produced by the corresponding genes. In conclusion, the present study, as in other recent studies we have conducted, demonstrated superior efficiency and reliability of the cFDR methodology for enhanced detection of trait-associated genetic variants. Our findings shed novel insight into the genetic variability of ALM in addition to the shared genetic basis underlying ALM and BMD.

A new type of electron microscope rapid collection device for atmospheric particles and its application cases.

A device for collecting atmospheric particulates matter for on-line electron microscopy was designed and manufactured by using 3D modeling and printing technology. The device was used to collect atmospheric particulates matter in Xining city of Qinghai province for seven consecutive days and used to collect atmospheric particulates matter in Jinan city of Shandong province for 30 consecutive days. And the samples were analyzed by electron microscopy. Through it can obtain ultra structure and size distribution information of atmospheric particulates matter. The experimental results reflected the distribution of atmospheric particulate matter in real time. The on-line acquisition device for electron microscopy is practical, fast, and convenient, which greatly shortens the sampling period and can be carried to any place outdoors for real-time sampling. The morphological structure and particle size distribution of atmospheric particles in sampling area was observed by electron microscope. The device has reference value to the study of PM2.5 and PM10 in atmosphere and air pollution. This acquisition device is convenient for the detection of sample by electron microscopy. It can further expand and simplify the sampling technology of large-scale instruments and equipment. This new method of real-time monitoring of air pollution is worth popularizing and applying.

Inhibition LC3B can increase chemosensitivity of ovarian cancer cells.

BACKGROUND: Ovarian cancer is often accompanied by the production of ascites, and patients with repeated ascites are associated with chemotherapy resistance. The previous study confirmed that the ovarian cancer patients who developed ascites after chemotherapy had elevated autophagy levels in the ascites and precipitated cells, which was positively correlated with MDR1 expression in the blood of patients. METHODS: In order to explore the correlation between autophagy and chemoresistant, we searched TCGA and GEO database to analyze the correlation between LC3B and MDR1, and identified the targeting miRNA of LC3B. It was verified by dual luciferase that miR-204 can target LC3B. The ovarian cancer cell line and the BALB/c nude mice tumor-bearing model were selected for in vitro and in vivo verification. In vitro studies confirmed that ovarian cancer cells were more sensitive to cisplatin by inhibiting LC3B. RESULTS: Overexpression of miR-204 reduced the expression of LC3B, Atg7, and MDR1, and promoted apoptosis. In vivo studies have also confirmed that reducing the level of autophagy in ovarian cancer cells increases the sensitivity to cisplatin. CONCLUSIONS: It suggests that miR-204 can be used as a tumor suppressor gene and LC3B expression level can be used as a potential molecular marker to guide the diagnosis and treatment of patients with ovarian cancer.

Tight N-observable uncertainty relations and their experimental demonstrations.

The uncertainty relation, as one of the fundamental principles of quantum physics, captures the incompatibility of noncommuting observables in the preparation of quantum states. In this work, we derive two strong and universal uncertainty relations for N(N ≥ 2) observables with discrete and bounded spectra, one in multiplicative form and the other in additive form. To verify their validity, for illustration, we implement in the spin-1/2 system an experiment with single-photon measurement. The experimental results exhibit the validity and robustness of these uncertainty relations, and indicate the existence of stringent lower bounds.

Sensitization and synergistic anti-cancer effects of Furanodiene identified in zebrafish models.

Furanodiene is a natural terpenoid isolated from Rhizoma Curcumae, a well-known Chinese medicinal herb that presents anticancer effects in various types of cancer cell lines. In this study, we have successfully established zebrafish xenografts with 5 various human cancer cell lines; and validated these models with anti-cancer drugs used clinically for treating human cancer patients. We found that Furanodiene was therapeutically effective for human JF 305 pancreatic cancer cells and MCF-7 breast cancer cells xenotranplanted into zebrafish. Furanodiene showed a markedly synergistic anti-cancer effect when used in combination with 5-FU (5-Fluorouracil) for both human breast cancer MDA-MB-231 cells and human liver cancer BEL-7402 cells xenotransplanted into zebrafish. Unexpectedly, Furanodiene reversed multiple drug resistance in the zebrafish xenotransplanted with cis-Platinum-resistant human non-small cell lung cancer cells and Adriamycin-resistant human breast cancer cells. Furanodiene played its anti-cancer effects through anti-angiogenesis and inducing ROS production, DNA strand breaks and apoptosis. Furanodiene suppresseed efflux transporter Pgp (P-glycoprotein) function and reduced Pgp protein level, but no effect on Pgp related gene (MDR1) expression. These results suggest sensitizition and synergistic anti-cancer effects of Furanodiene that is worthy of a further investigation.

Septation of the Intrapericardial Arterial Trunks in the Early Human Embryonic Heart.

BACKGROUND: Outflow tract (OFT) septation defects are a common cause of congenital heart disease. Numerous studies have focused on the septation mechanism of the OFT, but have reported inconsistent conclusions. This study, therefore, aimed to investigate the septation of the aortic sac and the OFT in the early embryonic human heart. METHODS: Serial sections of 27 human embryonic hearts from Carnegie stage (CS) 10 to CS19 were immunohistochemically stained with antibodies against α-smooth muscle actin (α-SMA) and myosin heavy chain. RESULTS: At CS10-CS11, the OFT wall was an exclusively myocardial structure that was continuous with the aortic sac at the margin of the pericardial cavity. From CS13 onward, the OFT was divided into nonmyocardial and myocardial portions. The cushion formed gradually, and its distal border with the OFT myocardium was consistently maintained. The aortic sac between the fourth and sixth aortic arch arteries was degenerated. At CS16, the α-SMA-positive aortopulmonary septum formed and fused with the two OFT cushions, thus septating the nonmyocardial portion of the OFT into two arteries. At this stage, the cushions were not fused. At CS19, the bilateral cushions were fused to septate the myocardial portion of the OFT. CONCLUSIONS: Data suggest that the OFT cushion is formed before the aortopulmonary septum is formed. Thus, the OFT cushion is not derived from the aortopulmonary septum. In addition, the nonmyocardial part of the OFT is septated into the aorta and pulmonary trunk by the aortopulmonary septum, while the main part of the cushion fuses and septates the myocardial portion of the OFT.

Corrigendum: A Stronger Multi-observable Uncertainty Relation.

This corrects the article DOI: 10.1038/srep44764.

A Necessary and Sufficient Criterion for the Separability of Quantum State.

Quantum entanglement has been regarded as one of the key physical resources in quantum information sciences. However, the determination of whether a mixed state is entangled or not is generally a hard issue, even for the bipartite system. In this work we propose an operational necessary and sufficient criterion for the separability of an arbitrary bipartite mixed state, by virtue of the multiplicative Horn's problem. The work follows the work initiated by Horodecki et al. and uses the Bloch vector representation introduced to the separability problem by J. De Vicente. In our criterion, a complete and finite set of inequalities to determine the separability of compound system is obtained, which may be viewed as trade-off relations between the quantumness of subsystems. We apply the obtained result to explicit examples, e.g. the separable decomposition of arbitrary dimension Werner state and isotropic state.

Highly Sensitive Detection of Melamine Based on the Fluorescence Resonance Energy Transfer between Conjugated Polymer Nanoparticles and Gold Nanoparticles.

Adding melamine as additives in food products will lead to many diseases and even death. However, the present techniques of melamine detection require time-consuming steps, complicated procedures and expensive analytical apparatus. The fluorescent assay method was facile and highly sensitive. In this work, a fluorescence resonance energy transfer (FRET) system for melamine detection was constructed based on conjugated polymer nanoparticles (CPNs) and gold nanoparticles (AuNPs). The energy transfer efficiency is up to 82.1%, and the system is highly selective and sensitive to melamine detection with a lower detection limit of 1.7 nmol/L. Moreover, the interaction mechanism was explored. The results showed that the fluorescence of CPNs were firstly quenched by AuNPs, and then restored after adding melamine because of reducing FRET between CPNs and AuNPs. Lastly, the proposed method was carried out for melamine detection in powdered infant formula with satisfactory results.