Normal Ones Research Articles

Lesion-Decoupling-Based Segmentation With Large-Scale Colon and Esophageal Datasets for Early Cancer Diagnosis.

Lesions of early cancers often show flat, small, and isochromatic characteristics in medical endoscopy images, which are difficult to be captured. By analyzing the differences between the internal and external features of the lesion area, we propose a lesion-decoupling-based segmentation (LDS) network for assisting early cancer diagnosis. We introduce a plug-and-play module called self-sampling similar feature disentangling module (FDM) to obtain accurate lesion boundaries. Then, we propose a feature separation loss (FSL) function to separate pathological features from normal ones. Moreover, since physicians make diagnoses with multimodal data, we propose a multimodal cooperative segmentation network with two different modal images as input: white-light images (WLIs) and narrowband images (NBIs). Our FDM and FSL show a good performance for both single-modal and multimodal segmentations. Extensive experiments on five backbones prove that our FDM and FSL can be easily applied to different backbones for a significant lesion segmentation accuracy improvement, and the maximum increase of mean Intersection over Union (mIoU) is 4.58. For colonoscopy, we can achieve up to mIoU of 91.49 on our Dataset A and 84.41 on the three public datasets. For esophagoscopy, mIoU of 64.32 is best achieved on the WLI dataset and 66.31 on the NBI dataset.

Resilient Consensus of Multiagent Systems Under Collusive Attacks on Communication Links.

This article addresses the resilient consensus problem of multiagent systems subject to cyber attacks on communication links, where the attacks on different links may collude to maintain undetectable. For the case with noncollusive attacks on links, a distributed fixed-time observer is designed so that the attack on each link can be detected by the two associated agents. A necessary and sufficient condition is derived to ensure the isolation of attacked links and no mistaken isolation of normal ones. For the case with collusive attacks on links, a novel attack isolation algorithm is proposed by constructing extra observers on the basis of the previous designed distributed fixed-time observer via sequentially removing the information associated with one of the links. Based on the isolation of the attacked links, a control algorithm is designed, and a necessary and sufficient condition is provided to achieve resilient consensus. Numerical examples corroborate the effectiveness of the proposed strategies.

Small-molecule inhibitor HI-TOPK-032 improves NK-92MI cell infiltration into ovarian tumours.

The effectiveness of natural killer (NK) cells transferred adoptively in combating solid tumours is limited by challenges such as their difficulty in penetrating tumours from the bloodstream and maintaining viability without the support of interleukin-2 (IL-2). Genetically modified NK-92MIcells, which can release IL-2 to sustain their viability, have been identified as a promising alternative. This adaptation addresses the negative consequences of systemic IL-2 administration. The role of PSD-95/discs large/ZO-1 (PDZ)-binding kinase (PBK) in cancer development is recognized, but its effects on immunity are not fully understood. This study explores how PBK expression influences the ability of NK-92MI cells to infiltrate ovarian tumours. Elevated levels of PBK expression have been found in various cancers, including ovarian cancer (OV), with analyses showing higher PBK mRNA levels in tumour tissues compared to normal ones. Immunohistochemistry has confirmed increased PBK expression in OV tissues. Investigations into PBK's role in immune regulation reveal its association with immune cell infiltration, indicating a potentially compromised immune environment in OV with high PBK expression. The small-molecule inhibitor HI-TOPK-032, which inhibits PBK, enhances the cytotoxicity of NK-92MI cells toward OV cells. It increases the production of interferon-γ and tumour necrosis factor-α, reduces apoptosis and encourages cell proliferation. Mechanistic studies showed that contact with OV cells treated with HI-TOPK-032 upregulates CD107a on NK-92 cells. In vivo studies demonstrated that HI-TOPK-032 improves the antitumour effects of NK-92MI cells in OVCAR3Luc xenografts, extending survival without significant side effects. Safety assessments in mice confirm HI-TOPK-032's favourable safety profile, highlighting its potential as a viable antitumour therapy. These results suggest that combining NK-92MI cells with HI-TOPK-032 enhances antitumour effectiveness against OV, indicating a promising, safe and effective treatment strategy that warrants further clinical investigation.

Attack as Detection: Using Adversarial Attack Methods to Detect Abnormal Examples

As a new programming paradigm, deep learning (DL) has achieved impressive performance in areas such as image processing and speech recognition, and has expanded its application to solve many real-world problems. However, neural networks and DL are normally black-box systems; even worse, DL-based software are vulnerable to threats from abnormal examples, such as adversarial and backdoored examples constructed by attackers with malicious intentions as well as unintentionally mislabeled samples. Therefore, it is important and urgent to detect such abnormal examples. Although various detection approaches have been proposed respectively addressing some specific types of abnormal examples, they suffer from some limitations; until today, this problem is still of considerable interest. In this work, we first propose a novel characterization to distinguish abnormal examples from normal ones based on the observation that abnormal examples have significantly different (adversarial) robustness from normal ones. We systemically analyze those three different types of abnormal samples in terms of robustness and find that they have different characteristics from normal ones. As robustness measurement is computationally expensive and hence can be challenging to scale to large networks, we then propose to effectively and efficiently measure robustness of an input sample using the cost of adversarially attacking the input, which was originally proposed to test robustness of neural networks against adversarial examples. Next, we propose a novel detection method, named attack as detection (A 2 D for short), which uses the cost of adversarially attacking an input instead of robustness to check if it is abnormal. Our detection method is generic, and various adversarial attack methods could be leveraged. Extensive experiments show that A 2 D is more effective than recent promising approaches that were proposed to detect only one specific type of abnormal examples. We also thoroughly discuss possible adaptive attack methods to our adversarial example detection method and show that A 2 D is still effective in defending carefully designed adaptive adversarial attack methods—for example, the attack success rate drops to 0% on CIFAR10.

Correlation between ferroptosis and adriamycin resistance in breast cancer regulated by transferrin receptor and its molecular mechanism.

Breast cancer is the most prevalent malignant tumor in women. Adriamycin (ADR) is a primary chemotherapy drug, but resistance limits its effectiveness. Ferroptosis, a newly identified cell death mechanism, involves the transferrin receptor (TFRC), closely linked with tumor cells. This study aimed to explore TFRC and ferroptosis's role in breast cancer drug resistance. Bioinformatics analysis showed that TFRC was significantly downregulated in drug-resistant cell lines, and patients with low TFRC expression might demonstrate a poor chemotherapeutic response to standard treatment. High expression of TFRC was positively correlated with most of the ferroptosis-related driver genes. The research findings indicate that ferroptosis markers were higher in breast cancer tissues than in normal ones. In chemotherapy-sensitive cases, Ferrous ion (Fe2+ ) and malondialdehyde (MDA) levels were higher than in resistant cases (all p < .05). TFRC expression was higher in breast cancer than in normal tissue, especially in the sensitive group (all p < .05). Cytological experiments showed increased hydrogen peroxide (H2 O2 ) after ADR treatment in both sensitive and resistant cells, with varying MDA changes (all p < .05). Elevating TFRC increased Fe2+ and MDA in ADR-resistant cells, enhancing their sensitivity to ADR. However, TFRC upregulation combined with ADR increased proliferation and invasiveness in resistant cell lines (all p < .05). In conclusion, ADR resistance to breast cancer is related to the regulation of iron ion-mediated ferroptosis by TFRC. Upregulation of TFRC in ADR-resistant breast cancer cells activates ferroptosis and reverses ADR chemotherapy resistance of breast cancer.

Parkinsons disease diagnosis through electroencephalographic signal processing and neural network classification

Parkinsons disease diagnosis through electroencephalographic signal processing and neural network classification

PH-responsive composite nanomaterial engineered from silica nanoparticles and luminescent mitochondrion-targeted Pt(II) complex as anticancer agent

The present work introduces a pH-dependent adsorption of water-soluble Pt(II) complex with diimine and alkynylphosphonium ligands ([Pt]2+) onto a surface of silica nanoparticles (SN-OH) as a strategy to develop a carrier function with an acidification-driven release of the complex. The adsorption of the complex onto a negatively charged silica surface shifts the equilibrium between dimeric and monomeric complex forms. The surface loading of [Pt]2+ is efficient at pH 7.0, and the acidification to pH 4.5 triggers the complex release. The interaction of [Pt]2+ with bovine serum albumin (BSA) influences the cell internalization and intracellular pathway of the complex, as well as the formation of the [Pt]2+-loaded SN-OH protein corona. The cytotoxicity data for the series of cancer and normal cell lines reveal the loading of [Pt]2+ into SN-OH as an efficient route for lower cytotoxicity and greater anticancer specificity of the nanoparticles compared to the complex. The flow cytometry and confocal microscopy methods reveal similarities in the cell internalization and intracellular pathway of [Pt]2+ and the [Pt]2+-loaded nanoparticles. The mitochondrial localization of [Pt]2+ and the [Pt]2+-loaded SN-OH does not cause noticeable changes in the membrane potential of mitochondria, and the cytotoxicity of [Pt]2+ in both forms is due to a non-apoptotic mechanism of cell death. Both the cytotoxicity and increased anticancer specificity of nanoparticles are associated with their carrier function, which is more pronounced in cancer cells with overdeveloped lysosomal compartments compared to normal ones.

Parabiosis Discriminates the Circulating, Endothelial, and Parenchymal Contributions of Endogenous Tissue-Type Plasminogen Activator to Stroke.

Intravenous injection of alteplase, a recombinant tPA (tissue-type plasminogen activator) as a thrombolytic agent has revolutionized ischemic stroke management. However, tPA is a more complex enzyme than expected, being for instance able to promote thrombolysis, but at the same time, also able to influence neuronal survival and to affect the integrity of the blood-brain barrier. Accordingly, the respective impact of endogenous tPA expressed/present in the brain parenchyma versus in the circulation during stroke remains debated. To address this issue, we used mice with constitutive deletion of tPA (tPANull [tPA-deficient mice]) or conditional deletion of endothelial tPA (VECad [vascular endothelial-Cadherin-Cre-recombinase]-Cre∆tPA). We also developed parabioses between tPANull and wild-type mice (tPAWT), anticipating that a tPAWT donor would restore levels of tPA to normal ones, in the circulation but not in the brain parenchyma of a tPANull recipient. Stroke outcomes were investigated by magnetic resonance imaging in a thrombo-embolic or a thrombotic stroke model, induced by local thrombin injection or FeCl3 application on the endothelium, respectively. First, our data show that endothelial tPA, released into the circulation after stroke onset, plays an overall beneficial role following thrombo-embolic stroke. Accordingly, after 24 hours, tPANull/tPANull parabionts displayed less spontaneous recanalization and reperfusion and larger infarcts compared with tPAWT/tPAWT littermates. However, when associated to tPAWT littermates, tPANull mice had similar perfusion deficits, but less severe brain infarcts. In the thrombotic stroke model, homo- and hetero-typic parabionts did not differ in the extent of brain damages and did not differentially recanalize and reperfuse. Together, our data reveal that during thromboembolic stroke, endogenous circulating tPA from endothelial cells sustains a spontaneous recanalization and reperfusion of the tissue, thus, limiting the extension of ischemic lesions. In this context, the impact of endogenous parenchymal tPA is limited.

3D hierarchic interfacial assembly of Au nanocage@Au along with IS-AgMNPs for simultaneous, ultrasensitive, reliable, and quantitative SERS detection of colorectal cancer related miRNAs

Simultaneous, reliable, and ultra-sensitive analysis of promising miRNA biomarkers of colorectal cancer (CRC) in serum is critical for early diagnosis and prognosis of CRC. In this work, we proposed a novel 3D hierarchic assembly clusters-based SERS strategy with dual enrichment and enhancement designed for the ultrasensitive and quantitative analysis of two upregulated CRC-related miRNAs (miR-21 and miR-31). The biosensor contains the following: (1) SERS probe, Au nanocage@Au nanoparticles (AuNC@Au NPs) labeled with Raman reporters (RaRs). (2) magnetic capture unit, Ag-coated Fe3O4 magnetic nanoparticles (AgMNPs) modified with internal standard (IS). (3) signal amplify probes (SA probes) for the formation of hierarchic assembly clusters. Based on this sensing strategy, the intensity ratio IRaRs/IIS with Lg miRNAs presents a wide linear range (10 aM–100 pM) with a limit of detection of 3.46 aM for miR-21, 6.49 aM for miR-31, respectively. Moreover, the biosensor shows good specificity and anti-interference ability, and the reliability and repeatability of the strategy were then verified by practical detection of clinical serum. Finally, the biosensor can distinguish CRC cancer subjects from normal ones and guide the distinct tumor, lymph node, and metastasis (TNM) stages. Overall, benefiting from the face-to-face coupling of hierarchic assembly clusters, rapid magnetic enrichment and IS signal calibration of AgMNPs, the established biosensor achieves ultra-sensitive and simultaneous detection of dual miRNAs and opens potential avenues for prediction and staging of CRC.

Quantitative evaluation of dielectrophoretic separation efficiency of cancer exosomes based on fluorescence imaging

Liquid biopsies for cancer diagnosis using exosomes have been studied. Separating cancer cell-derived exosomes from a sample mixture is crucial, especially when they do not dominate the sample at an early stage of cancer. A method based on their electrical properties could provide a simpler separation than immune-affinity methods. We have identified the differences in electrical properties of cancerous exosomes from those of normal ones, suggesting the possibility for their dielectrophoresis (DEP) based separation. This study separated cancerous exosomes from a mixture of normal exosomes. The DEP of fluorescence-labeled exosomes suspended in aqueous media with varying electrical conductivities was investigated. The observed DEP was quantitatively evaluated using the normalization method accounting for the fluorescence fading effect. The results showed that the cancerous exosomes were preferentially concentrated under the appropriate conditions. This suggests that DEP can enable the selective capture of cancer exosomes without chemical labeling.

GD3N: Adaptive clustering-based detection of selective forwarding attacks in WSNs under variable harsh environments

Wireless sensor networks (WSNs) are susceptible to numerous security threats due to their reliance on open environments and broadcast communication methods. Among these, the selective forwarding attack is notably challenging to detect. This difficulty arises from the ability of malicious nodes to imitate the behavior of normal nodes, and selectively drop data packets, which makes them virtually indistinguishable from normal ones, particularly under conditions of poor channel quality. To address this challenge with harsh environments, we introduce a novel methodology termed GD3N. This approach is underpinned by the design of a unique type of data point that encapsulates both short-term and long-term forwarding behaviors of nodes. It combines a refined version of the Gradient Diffusion Density-based Spatial Clustering of Applications with Noise (GD-DBSCAN) algorithm, with a novel Double-Parameter Neighbor Voting (DP-NV) method based on the data set. These innovations contribute to a significant enhancement in detection accuracy and a reduction in computational complexity when compared to traditional DBSCAN and NV methods. Simulation results show that our GD3N achieves a false detection rate (FDR) of less than 2%, a missed detection rate (MDR) of below 10%, and an overall detection accuracy rate (DAR) of over 95% across various testing scenarios.

Elucidating Hedgehog pathway's role in HNSCC progression: insights from a 6-gene signature

With the emergence of targeted inhibition strategies for Hedgehog signaling in cancer, multiple Hedgehog signaling pathway-related biomarkers have become the focus of research. SsGSEA algorithm was employed to analyze the Hedgehog pathway scores of samples in TCGA-HNSC dataset and divide them into two groups. Weighted co-expression network analysis was performed to identify modules strongly associated with the Hedgehog pathway. Differentially up-regulated genes in tumor samples in comparison to the normal ones were screened by Limma, in which genes belonging to modules strongly related to Hedgehog pathway were further filtered by LASSO reduction and multivariate Cox regression analysis to develop a model. ESTIMATE and CIBERSORT were served to characterize the tumor microenvironment (TME). TIDE assessed immunotherapy response. Hedgehog pathway activity was significantly higher in head and neck squamous cell carcinoma (HNSCC) tissues than in normal tissues and was correlated with HNSCC survival, glycan, cofactors and vitamins, drug metabolism, and matrix scores. Six genes (SLC2A3, EFNB2, OAF, COX4I2, MT2A and TXNRD1) were captured to form a Hedgehog associated 6-gene signature, and the resulting risk score was an independent indicator of HNSCC prognosis. It was significantly positively correlated with stromal score, metabolism, angiogenesis and inflammatory response. Patients in low-risk group with a low TIDE score had higher immunotherapy sensitivity relative to those in high-risk group. This study revealed novel findings of the Hedgehog pathway in HNSCC progression and opened up a Hedgehog pathology-related signature to help identify risk factors contributing to HNSCC progression and help predict immunotherapy outcomes.

Association of Diabetic Retinopathy and Sleep Quality

Sleep disorders are more common in diabetes mellitus (DM) cases rather than normal ones. In addition, this condition could be associated with diabetic retinopathy (DR) development with more inflammatory indices in circulation. In the present study, we have evaluated the association between DR and sleep quality. This cross-sectional study is a part of the second phase of the study of the elderly cohort of Amirkola City, which was conducted in 2015-2016 on all people aged 60 and higher. Of all diabetic cases, 44 cases had retinopathy and were selected as the case group. To compare two control groups, 135 diabetic patients without retinopathy and 135 people without diabetes were randomly selected. The presence and type of retinopathy were determined based on an eye physical examination by an ophthalmologist. In addition, sleep quality was evaluated based on the Pittsburgh Questionnaire. The obtained data were analyzed by ANOVA, t-test, and linear regression tests. In the present study, there was a significant difference in the score of the Pittsburgh questionnaire between people with DR (45.5±68.2) compared to diabetic people without retinopathy (76.5±48.2) and people without diabetes (95.4±36.2) (P=0.470), but diabetic people without retinopathy had significantly worse sleep quality than people without diabetes (P=0.019). Also, sleep quality in women with DR was worse than in men (P=014). In the linear regression analysis, it was observed that age, gender, diabetes, and history of depression significantly affect the sleep quality of the evaluated cases (P&lt;0.05 for all). According to the results of the present study, DR does not negatively influence the quality of sleep, and DR is not related to sleep disorders.

Thermally-responsive and reduced glutathione-sensitive folate-targeted nanocarrier based on alginate and pluronic F127 for on-demand release of methotrexate

A specific rheumatoid arthritis (RA)-microenvironment-triggered nanocarrier for RA treatment of a first-line antirheumatic drug (Methotrexate, MTX) has been proposed. Reduced glutathione (GSH) responsivity, cystamine, was first introduced on the alginate backbone, which was then used as the bridge to connect pluronic F127 (temperature-responsive factor) and folic acid (targeting factor for active immune cells), resulting in dual-responsive triggered targeting carrier, PCAC-FA. In vitro study demonstrated that PCAC-FA was preferentially taken up by activated macrophage cells rather than normal ones, suggesting the targeting of PCAC-FA to inflamed tissue. The loading capacity of the designed carrier was 21.23 ± 0.91 %. MTX from the PCAC-FA carrier was significantly accelerated release in the presentation of glutathione or in cold shock condition, proposing the efficacy-controlled release. MTX@PCAC-FA showed excellent hemocompatibility, confirming a suitable application with parenteral administration. Notably, the acute and subacute toxicity in the mice model showed that the toxicity of MTX had significantly reduced after encapsulating in the PCAC-FA carrier. These nanoplatforms not only provide an alternative safe strategy for the clinical treatment of rheumatoid arthritis with MTX but also deliver MTX selectively and provide on-demand drug release via external and internal signals, thus emerging as a promising therapeutic option for precise RA therapy.

In Vitro Anticancer and Cytotoxic Activity of Ethanolic Extract of Phyllanthus reticulatus Poir. Against Hela Cell Line and Vero Cell Line

The present study was designed to investigate the anticancer activity of Phyllanthus reticulatus Poir. against HeLa cell line and to predict the therapeutic potential by investigating the cytotoxicity of the extract against Vero cell line and determining the selectivity index (SI). Phytochemical screening of the ethanolic extract of Phyllanthus reticulatus Poir. was employed by using standard methods. Anticancer and cytotoxic activities were investigated from Centre for Advanced Research in Science using their commercial services. MTT assay was employed for the evaluation of the activities. The concentrations of the extract was 5 mg/ml, 2.5 mg/ml, 1.25 mg/ml and 0.625 mg/ml. From the survival rate % inhibition was calculated and graphically the IC50 value was determined by plotting the % inhibition against the concentration of the extract investigated. Finally, the selectivity index was calculated from the IC50 values of the extract against HeLa cell line and Vero cell line. Glycoside, tannin, alkaloid, flavonoid, phenol, coumarin were present in the ethanolic extract of Phyllanthus reticulatus Poir. The IC50 value of the extract against HeLa Cell and Vero Cell were 1.00 mg/ml and 8.09 mg/ml respectively. The selectivity index was 8.09. This value indicates that the cancer cell (HeLa cells) will be killed at higher rate than normal ones i.e. the extract is more toxic for cancer cells.

The design of TOPK inhibitors using similarity search, molecular docking, and MD simulations

Cancer is still a major cause of death worldwide. Unfortunately, the majority of current anticancer treatments suffer many limitations, mainly emergence of resistance and lack of selectivity which necessitate the search for new therapeutics. The TOPK enzyme emerges as a promising target due to its overexpression in many cancer types while being rarely detected in normal tissues. Therefore, targeting TOPK would affect the malignant activity of cancerous cells while sparing normal ones. Further, its vital role in cell division, particularly in cytokinesis, adds to its safety to normal non-multiplying cells. In this study, a combined ligand and structure-based approach was utilized to identify potential TOPK inhibitors. Previously, we identified TOPK inhibitors using a structure-based approach following the construction of a 3D homology model of the TOPK enzyme. Herein, the most active identified inhibitor (lead) was used as a search query to conduct similarity search against PubChem and ChemBridge databases. Retrieved hits were filtered using drug-like filters, docked into the ATP binding site of the enzyme, and finally, the binding free energies of all docked poses were calculated. Based on the computational scores, eight hits were selected as potential TOPK inhibitors. The predicted ADMET descriptors of the eight selected hits were generally favorable. Further, MD simulations of the top scoring hit were conducted to investigate its binding dynamics compared to the lead compound and OTS964 which agreed with the docking results and propose the selected hits as potential TOPK inhibitors. Yet, biochemical testing is still needed to validate these results. Communicated by Ramaswamy H. Sarma

Progenesis in dicyemids

AbstractDicyemids (Phylum Dicyemida) are the most common and characteristic endosymbiont living in the renal sac of benthic cephalopod molluscs. Precocious development of a hermaphroditic gonad occurs in the larvae and smaller juveniles of 40 dicyemid species from 17 cephalopod species so far and is the usual phenomenon in dicyemids. Based on the developmental and morphological features of precocious individuals, progenesis (a form of heterochrony) is the appropriate term for such precocious development. In general, progenetic individuals have much lower fecundity than normal ones because of their smaller body size, and therefore, it appears to be a disadvantageous reproductive trait. Nonetheless, the number of progenetic individuals consists of 30%–50% of the population, a relatively large proportion suggesting that the presence of progenetic individuals probably plays an important role in life history strategy. Precocious development significantly reduces growth time and enables early maturation. Progenetic individuals are common in short‐living cephalopod species, in which precocious development seems appropriate for dicyemids, enabling fast larval release before the end of the host's life span.

Intrinsic dual emissive insulin capped Au/Ag nanoclusters as single ratiometric nanoprobe for reversible detection of pH and temperature and cell imaging

pH and temperature are two important characteristics in cells and the environment. These, not only in the well-done regulation of cell functions but also in diagnosis and treatment, have a key role. Protein-protected bimetallic nanoclusters are abundantly used in the building of biosensors. However, insulin-stabilized Au–Ag nanoclusters with dual intrinsic emission have not been investigated yet. In this work, Dual emissive insulin templated Au–Ag nanocluster (Ins(Au/Ag)NCs) were first synthesized in a simple and green one-put manner. The two emission wavelengths of, as-prepared NCs centered at 410 and 630 nm, excited in one excitation wavelength (330 nm). These two emission peaks were assigned to the di-Tyrosine cross-linked formation and bimetallic nanoclusters respectively. Further analysis displayed that each emission band of Ins(Au/Ag)NCs responded to one variable whilst another peak remained constant; For blue and red emission wavelengths, pH dependency and thermo-responsibility were observed respectively. As-prepared nanoprobe with the intrinsic dual emissive feature was used for ratiometric determination of these parameters, each with a discrete response from another. The linear range of 6.0–9.0 for pH and 1 to 71 °C for temperature was obtained, which comprises the physiological range of pH and temperature and afforded intracellular sensing and imaging capability. As-prepared NCs probe show excellent biocompatibility and cell membrane permeability, and so were successfully applied as direct ratiometric pH and temperature probes in HeLa and HFF cells. More interestingly, this dual emissive nanoprobe is capable of distinguishing cancer cells from normal ones.

Abnormal states with unequal constituent masses

The Bethe–Salpeter equation for system of two oppositely charged particles not only reproduces the Coulomb spectrum, but, for enough large coupling constant C>π4\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\mathcal C}>\\frac{\\pi }{4}$$\\end{document}, predicts additional levels not predicted by the Schrödinger equation. These relativistic states (called abnormal), in contrast to the normal ones, are dominated, for more than 90–99%, by Fock states involving the exchange particles—the photons, whereas contribution of two massive charged particles themselves is rather small (1–10%). Since the carrier of a large (positive) charge is a heavy ion, and the negative charge is provided by electron, the masses of two constituents are very different. It is shown that in a system with so different masses the abnormal states still exist. Moreover, the effect of unequal masses is attractive. The balance between photons and charged constituents is weakly sensitive to the mass ratio, so the photons still predominate.

The expression of SLFN11 is related to the sensitivity of bladder cancer cells to DNA damage agents

BackgroundPutative DNA/RNA helicase Schlafen-11 (SLFN11) was studied for its functions in cancer cells in current years, especially its ability of sensitizing cancer cells to DNA-damaging agents (DDA). However, little is known about the roles it plays in bladder cancer. MethodsBioinformatic tools including GEPIA, UALCAN, MEXPRESS, CTRP, cBioPortal, MethSurv, and Metascape were used. RT-qPCR, CCK-8 assay, and methylation specific PCR were used to verify the results of bioinformatic analysis in bladder cancer cells. ResultsCompared to the normal samples, the expression of SLFN11 was lower in BLCA samples. SLFN11 expression was associated with clinical parameters in BLCA patients, especially histological and molecular subtypes. Besides, its expression correlated to the sensitivity of cancer cells to DDA. Furthermore, the frequency of SLFN11 genetic alterations was low in BLCA patients, and methylationwas significantly negatively related to SLFN11 expression. The mRNA levels of SLFN11 in the bladder cancer cells UMUC-3, T24, and T24-GR were significantly lower than that in the normal SV-HUC-1 cells. SLFN11 expression was positively correlated with bladder cancer cells’ sensitivity to gemcitabine. In addition, partial methylation of SLFN11 was detected in T24-GR, and can be inhibited by 5-Aza. ConclusionsSLFN11 expression was lower in BLCA samples and in vitro bladder cancer cells than in the normal ones. The level of SLFN11 correlated to the sensitivity of cancer cells to DDA. Additionally, the methylation of SLFN11 was negatively related to its expression. It couldbe a potential prognostic biomarker for predicting the therapeutic effect of DNA-damaging agents in patients with bladder cancers.