Localization Action Research Articles

Front Cover: Synthesis, Subcellular Localization and Anticancer Mechanism Studies of Unsymmetrical Iridium(III) Complexes (Eur. J. Inorg. Chem. 15/2023)

The Front Cover shows the synthesis, subcellular localization, and anticancer action mechanism of two novel unsymmetrical Ir(III) complexes, Ir1 and Ir2. Ir1 is mainly located in mitochondria. In contrast, Ir2 accumulates in mitochondria but subsequently migrates to the nucleus. Ir1 and Ir2 showed cytotoxicity toward cancerous cells, especially the cisplatin-resistant ones. Although both Ir1 and Ir2 disrupted the mitochondrial metabolism, they showed different cell death mechanisms. Ir1 induced mitochondria-mediated apoptosis in cisplatin-resistant A549R cells. Ir2 was demonstrated to cause PARP-1 activated necroptosis in A549R cells. This study provides an experimental basis for the rational design of metal-based chemotherapeutic drugs. More information can be found in the Research Article by Y. Chen, J. Long, H. Chao and co-workers.

Halogen-free photosensitizers based on meso-enamine-BODIPYs for bioimaging and photodynamic therapy.

The search for efficient heavy atom free photosensitizers (PSs) for photodynamic therapy (PDT) is a very active field. We describe herein a simple and easily accessible molecular design based on the attachment of an enamine group as an electron-donor moiety at the meso position of the BODIPY core with different alkylation patterns. The effect of the alkylation degree and solvent polarity on the photophysical properties in terms of splitting absorption bands, fluorescence efficiencies and singlet oxygen production is analyzed in depth experimentally using spectroscopic techniques, including femtosecond and nanosecond transient absorption (fs- and ns-TA) and using computational simulations based on time-dependent density functional theory. The correlation between the theoretical/experimental results permits the rationalization of the observed photophysical behavior exhibited by meso-enamine-BODIPY compounds and the determination of mechanistic details, which rule the population of the triplet state manifold. The potential applicability as a theragnostic agent for the most promising compound is demonstrated through in vitro assays in HeLa cells by analyzing the internalization, localization and phototoxic action.

Skeleton-Based Mutually Assisted Interacted Object Localization and Human Action Recognition

Skeleton data carries valuable motion information and is widely explored in human action recognition. However, not only the motion information but also the interaction with the environment provides discriminative cues to recognize the action of persons. In this paper, we propose a joint learning framework for mutually assisted ''interacted object localization'' and ''human action recognition'' based on skeleton data. The two tasks are serialized together and collaborate to promote each other, where preliminary action type derived from skeleton alone helps improve interacted object localization, which in turn provides valuable cues for the final human action recognition. Besides, we explore the temporal consistency of interacted object as constraint to better localize the interacted object with the absence of ground-truth labels. Extensive experiments on the datasets of SYSU-3D, NTU60 RGB+D, Northwestern-UCLA and UAV-Human show that our method achieves the best or competitive performance with the state-of-the-art methods for human action recognition. Visualization results show that our method can also provide reasonable interacted object localization results.

Localization and gene action studies for kernel iron and zinc concentration in groundnut (Arachis hypogaea L.)

Localization and gene action studies for kernel iron and zinc concentration in groundnut (Arachis hypogaea L.)

Novel Protonic Neuron Theory: Bettering the Fundamental Understanding of Action Potential and Neural Stimulation

Through biophysical chemistry analyses applying the transmembrane electrostatic proton localization theory, neural resting and action potential is now much better understood as the voltage contributed by the localized protons/cations at a neural liquid-membrane interface. Accordingly, the neural resting/action potential is essentially a protonic/cationic membrane capacitor behavior. It is now understood with a newly formulated protonic neural action potential equation: when action potential is below zero (negative number), the localized protons/cations charge density at the liquid-membrane interface along the periplasmic side are above zero (positive number); when the action potential is above zero, the concentration of the localized protons and localized non-proton cations is below zero, indicating a “depolarization” state. The nonlinear curve of localized protons/cations charge density in the time domain of an action potential spike appears as an inverse mirror image to the action potential signal. The protonic action potential equation provides biophysical insights for neuron electrophysiology, which may represent a complementary development to the classic Goldman-Hodgkin-Katz equation. Using the protonic neural action potential equation, the biological significance of axon myelination is now also elucidated as to provide protonic insulation and prevent any ions both inside and outside the neuron from interfering with the action potential signal, so that the action potential can quickly propagate along the axon with minimal (e.g., 40-times less) energy requirement. This new finding may have scientific implications also to better the fundamental understanding of neural stimulation in relation to the firing and propagation of action potential signals in neurons.

Laser-induced photothermal generation of flexible and salt-resistant monolithic bilayer membranes for efficient solar desalination

Harvesting solar energy and generating steam through solar thermal energy are viable approaches with diverse applications such as power generation, desalination, and water purification. Particularly, for efficient and stable solar desalination, hierarchically porous materials are desired to enable the required multiple functionalities. However, high thermal/chemical energy required and time consumed remain roadblocks. In this study, a facile, fast, and scalable laser-induced photothermal method to achieve flexible monolithic bilayer sheets (MBS) of hierarchically porous graphitic carbon (HPGC) and polymeric foam for use in salt-resistant and flexible solar steam generators is reported. The MBS-based self-floating solar steam generator shows outstanding solar desalination performance with a solar thermal efficiency of 83.2% (1-sun) and a high salt-rejection ratio (99.9%). Efficient solar thermal energy transformation is achieved by the versatile multi-functionalities of the MBS, including broad-spectrum solar light absorption, heat localization, and capillary action. Anisotropic wetting properties of hydrophobic HPGC and hydrophilic polyimide (PI) foam effectively prevent salt accumulation on the HPGC surface. The salt-resistant MBS enable long-term stability for solar desalination with actual seawater. Our laser-based photothermal method has potential in the development of high-performance solar thermal systems with substantial cost reduction by scalable production of multiscale hierarchically structured materials from micro-structured polymers.

Bioenergetics of the Dictyostelium Kinesin-8 Motor Isoform.

The functional organization of microtubules in eukaryotic cells requires a combination of their inherent dynamic properties, interactions with motor machineries, and interactions with accessory proteins to affect growth, shrinkage, stability, and architecture. In most organisms, the Kinesin-8 family of motors play an integral role in these organizations, well known for their mitotic activities in microtubule (MT) length control and kinetochore interactions. In Dictyostelium discoideum, the function of Kinesin-8 remains elusive. We present here some biochemical properties and localization data that indicate that this motor (DdKif10) shares some motility properties with other Kinesin-8s but also illustrates differences in microtubule localization and depolymerase action that highlight functional diversity.

Biological Effects of a Simplified Synthetic Analogue of Ion-Channel-Forming Polytheonamide B on Plasma Membrane and Lysosomes.

Polytheonamide B (1) is a linear 48-mer natural peptide with alternating d- and l-amino acid residues. Compound 1 forms conducting channels for monovalent ions and exhibits potent cytotoxicity against MCF-7 cells. Previously, we reported that nanomolar concentrations of 1 induce plasma membrane depolarization and lysosomal pH disruption, which triggers apoptosis. Here, we report the cellular localization and biological action of a simplified synthetic analogue of 1, polytheonamide mimic 3. Compared with 1, the toxicity of 3 against MCF-7 cells is 16 times weaker. Although its plasma membrane depolarization effect is only 3.6 times lower, more 3 (20-fold) is required to neutralize lysosomal pH. Thus, the effective concentrations for lysosomal neutralization and cytotoxicity by 3 are comparable. These results strongly suggest that the activity of 3 against the lysosomal membrane is more important for apoptotic cell death than its effects on the plasma membrane, and provide valuable information regarding the unique behavior of polytheonamide-based molecules.

An overview on wireless sensor networks and finding optimal location of nodes

In this review, our aim is to make a brief description about technology of Wireless Sensor Network (WSN) and its capability to pave the way in order to make connection between physical and virtual world based on Internet worldwide network. Hence, in this technology, sensor nodes play an important role to transmit data from a node to other defined nodes in its broaden range. Due to gain most optimal state from WSNs, subject of localization for radio frequency networks has a great importance in many technical applications such as military devices to detect specified local points to attack or defend, civil engineering and in general sensor networks. The main technology to obtain direct locations is GPS (Global Positioning System). After expressing a brief history on introduction part, we will go through in order to interrogate on main structure of WSNs regarding mathematical formulations and algorithms to find best and optimal access points based on Localization action. Then, we summarize algorithms and approaches to develop in order to introduce the best strategy in order to access nodes in the best possible state in WSNs. As a result, we conclude about the mentioned issues in order of comparison and reaching a final result. Therefore, final aim of this review is to explain efficiency and reliability of localization based on different opinions. Results show this overwhelming technology can be completely modified in order to find new solutions to find nodes in most optimal nodes based on spontaneous structure of WSNs.

Human-Like Delicate Region Erasing Strategy for Weakly Supervised Detection

We explore a principle method to address the weakly supervised detection problem. Many deep learning methods solve weakly supervised detection by mining various object proposal or pooling strategies, which may cause redundancy and generate a coarse location. To overcome this limitation, we propose a novel human-like active searching strategy that recurrently ignores the background and discovers class-specific objects by erasing undesired pixels from the image. The proposed detector acts as an agent, providing guidance to erase unremarkable regions and eventually concentrating the attention on the foreground. The proposed agents, which are composed of a deep Q-network and are trained by the Q-learning algorithm, analyze the contents of the image features to infer the localization action according to the learned policy. To the best of our knowledge, this is the first attempt to apply reinforcement learning to address weakly supervised localization with only image-level labels. Consequently, the proposed method is validated on the PASCAL VOC 2007 and PASCAL VOC 2012 datasets. The experimental results show that the proposed method is capable of locating a single object within 5 steps and has great significance to the research on weakly supervised localization with a human-like mechanism.

An Overview on Wireless Sensor Networks and Finding Optimal Location of Nodes

In this review, our aim is to make a brief description about technology of Wireless Sensor Network (WSN) and its capability to pave the way in order to make connection between physical and virtual world based on Internet worldwide network. Hence, in this technology, sensor nodes play an important role to transmit data from a node to other defined nodes in its broaden range. Due to gain most optimal state from WSNs, subject of localization for radio frequency networks has a great importance in many technical applications such as military devices to detect specified local points to attack or defend, civil engineering and in general sensor networks. The main technology to obtain direct locations is GPS (Global Positioning System). After expressing a brief history on introduction part, we will go through in order to interrogate on main structure of WSNs regarding mathematical formulations and algorithms to find best and optimal access points based on Localization action. Then, we summarize algorithms and approaches to develop in order to introduce the best strategy in order to access nodes in the best possible state in WSNs. As a result, we conclude about the mentioned issues in order of comparison and reaching a final result. Therefore, final aim of this review is to explain efficiency and reliability of localization based on different opinions. Results show this overwhelming technology can be completely modified in order to find new solutions to find nodes in most optimal nodes based on spontaneous structure of WSNs.

Exploring frame segmentation networks for temporal action localization

Temporal action localization is an important task of computer vision. Though many methods have been proposed, it still remains an open question how to predict the temporal location of action segments precisely. Most state-of-the-art works train action classifiers on video segments pre-determined by action proposal. However, recent work found that a desirable model should move beyond segment-level and make dense predictions at a fine granularity in time to determine precise temporal boundaries. In this paper, we propose a Frame Segmentation Network (FSN) that places a temporal CNN on top of the 2D spatial CNNs. Spatial CNNs are responsible for abstracting semantics in spatial dimension while temporal CNN is responsible for introducing temporal context information and performing dense predictions. The proposed FSN can make dense predictions at frame-level for a video clip using both spatial and temporal context information. FSN is trained in an end-to-end manner, so the model can be optimized in spatial and temporal domain jointly. We also adapt FSN to use it in weakly supervised scenario (WFSN), where only video level labels are provided when training. Experiment results on public dataset show that FSN achieves superior performance in both frame-level action localization and temporal action localization.

Looking Beyond Energy Efficiency: An Applied Review of Water Desalination Technologies and an Introduction to Capillary-Driven Desalination

Most notable emerging water desalination technologies and related publications, as examined by the authors, investigate opportunities to increase energy efficiency of the process. In this paper, the authors reason that improving energy efficiency is only one route to produce more cost-effective potable water with fewer emissions. In fact, the grade of energy that is used to desalinate water plays an equally important role in its economic viability and overall emission reduction. This paper provides a critical review of desalination strategies with emphasis on means of using low-grade energy rather than solely focusing on reaching the thermodynamic energy limit. Herein, it is argued that large-scale commercial desalination technologies have by-and-large reached their engineering potential. They are now mostly limited by the fundamental process design rather than process optimization, which has very limited room for improvement without foundational change to the process itself. The conventional approach toward more energy efficient water desalination is to shift from thermal technologies to reverse osmosis (RO). However, RO suffers from three fundamental issues: (1) it is very sensitive to high-salinity water, (2) it is not suitable for zero liquid discharge and is therefore environmentally challenging, and (3) it is not compatible with low-grade energy. From extensive research and review of existing commercial and lab-scale technologies, the authors propose that a fundamental shift is needed to make water desalination more affordable and economical. Future directions may include novel ideas such as taking advantage of energy localization, surficial/interfacial evaporation, and capillary action. Here, some emerging technologies are discussed along with the viability of incorporating low-grade energy and its economic consequences. Finally, a new process is discussed and characterized for water desalination driven by capillary action. The latter has great significance for using low-grade energy and its substantial potential to generate salinity/blue energy.

Effect of dose responses of hydrophilic aluminium (III) phthalocyanine chloride tetrasulphonate based photosensitizer on lung cancer cells

Photodynamic therapy (PDT) is a promising approach for the treatment of different types of cancer and has been brought into focus for its synergy, compatibility, repeatability, relatively inexpensive cost and it's typically more efficacious nature. Photosensitizers (PSs) play a major role in PDT and are the core of this specific therapy. Al (III) Phthalocyanine Chloride Tetra sulfonic Acid (AlPcS4Cl) PS is an aromatic macrocyclic metal-based compound that is synthetically derived. It aids in deep tissue penetration due to its far red light activation wavelength, low photo bleaching, increased quantum yields and stability. Lung cancer is a leading cause of cancer related deaths worldwide accounting for approximately 1 in 5 of all cancer-related deaths. In this study, we explored the photochemical properties of AlPcS4Cl, its uptake into lung cancer, the intracellular localization and photodynamic action on lung cancer (A549 cells). Results indicated that AlPcS4Cl is a stable PS that localizes in intracellular organelles including the mitochondrion and lysosomes. PDT using AlPcS4Cl indicated an increase in cell death and decrease in cell proliferation and viability. AlPcS4Cl showed to be effective in treating lung cancer in vitro, however the resulting PDT efficacy will finally depend on the biological features such as tumour vasculature and tumour specific accumulation when used as a clinical application. It is noted that PDT can be considered as an adjunct therapy until standard protocols for various tumour types along with a relevant PS has been validated.

Segment-Tube: Spatio-Temporal Action Localization in Untrimmed Videos with Per-Frame Segmentation.

Inspired by the recent spatio-temporal action localization efforts with tubelets (sequences of bounding boxes), we present a new spatio-temporal action localization detector Segment-tube, which consists of sequences of per-frame segmentation masks. The proposed Segment-tube detector can temporally pinpoint the starting/ending frame of each action category in the presence of preceding/subsequent interference actions in untrimmed videos. Simultaneously, the Segment-tube detector produces per-frame segmentation masks instead of bounding boxes, offering superior spatial accuracy to tubelets. This is achieved by alternating iterative optimization between temporal action localization and spatial action segmentation. Experimental results on three datasets validated the efficacy of the proposed method, including (1) temporal action localization on the THUMOS 2014 dataset; (2) spatial action segmentation on the Segtrack dataset; and (3) joint spatio-temporal action localization on the newly proposed ActSeg dataset. It is shown that our method compares favorably with existing state-of-the-art methods.

A comparative study on in vitro cytotoxicity, cellular uptake, localization and apoptosis-inducing mechanism of two ruthenium(II) complexes

Two ruthenium complexes [Ru(MeIm)4(bpy)]2+ (Ru1, MeIm = 1-methylimidazole, bpy = 2,2′-bipyridine) and [Ru(Im)4(bpy)]2+ (Ru2, Im = imidazole) with the same PF 6 − counter-ion but different lipophilicities were synthesized and characterized and as potent anticancer agents. The relationships between cellular uptake, localization and molecular action mechanisms of these complexes were elucidated. The results showed that Ru1 with higher logPo/w exhibited faster cellular uptake rates, but lower anticancer activity than Ru2. In addition, Ru1 predominantly accumulated in the mitochondria and cytoplasm, and induced G0/G1 cell cycle arrest, whereas the more hydrophilic Ru2 tended to localize and accumulate in the cell nucleus and mitochondria. Further mechanism studies indicated that Ru2 caused cell cycle arrest at S phase by regulating cell cycle related proteins and induced apoptosis in A549 cells through DNA damage, cellular ROS accumulation, activation of the caspase pathway and mitochondrial dysfunction.

Cellular localization of iron(II) polypyridyl complexes determines their anticancer action mechanisms

Elucidation of relationship among cellular uptake, localization and biological activities of metal complexes could make great breakthrough in the understanding of their action mechanisms and provide useful information for rational design of metal-based anticancer drugs. Iron(II) complexes have emerged as potential anticancer drug candidates with application potential in cancer imaging and therapy. Herein, a series of iron(II) polypyridyl complexes with different lipophilicity were rationally designed, synthesized and identified as potent anticancer agents. The relationship between the cellular localization and molecular action mechanisms of the complexes was also elucidated. The results showed that, the increase in planarity of the Fe(II) polypyridyl complexes enhanced their lipophilicity and cellular uptake, leading to improved anticancer efficacy. The hydrophilic Fe(II) complex entered cancer cells through transferring receptor (TfR)-mediated endocytosis, and translocated to cell nucleus, where they induced S phase cell cycle arrest through triggering DNA damage-mediated p53 pathway. Interestingly, the hydrophobic Fe(II) complexes displayed higher anticancer efficacy than the hydrophilic ones, but shared the same uptake pathway (TfR-mediated endocytosis) in cancer cells. They accumulated and localized in cell cytoplasm, and induced G0/G1 cells cycle arrest through regulation of AKT pathway and activation of downstream effector proteins. These results support that the cellular localization of Fe(II) complexes regulated by their lipophilicity could affect the anticancer efficacy and action mechanisms. Taken together, this study may enhance our understanding on the rational design of the next-generation anticancer metal complexes.

EHSP70/iHSP70 and divergent functions on the challenge: effect of exercise and tissue specificity in response to stress.

Heat-shock proteins including HSP70 are stress-related proteins that have been reported in cell protection and survival. In contrast to this, the increase in circulating levels of HSP70 (eHSP70) is associated with cellular damage and inflammatory factors. Physical stress, like exercise, is effective to induce both iHSP70 and eHSP70 in several tissues and cell types, which have different behaviours in response to stress. The different functions of HSP70 before the challenge are dependent of intracellular localization and subsequent molecular chaperone action, but when present in the extracellular space, it activates pro-inflammatory pathways. The different forms in which tissues and cells respond to stress like physical exercise, as well as the optimal intensity of the stress, are determinants for the beneficial effects or as an indicator of dangerous conditions, summoning immune cells as a warning sign to the body.

A Comprehensive Tutorial onIn VitroCharacterization of New Photosensitizers for Photodynamic Antitumor Therapy and Photodynamic Inactivation of Microorganisms

In vitro research performed on eukaryotic or prokaryotic cell cultures usually represents the initial step for characterization of a novel photosensitizer (PS) intended for application in photodynamic therapy (PDT) of cancer or photodynamic inactivation (PDI) of microorganisms. Although many experimental steps of PS testing make use of the wide spectrum of methods readily employed in cell biology, special aspects of working with photoactive substances, such as the autofluorescence of the PS molecule or the requirement of light protection, need to be considered when performing in vitro experiments in PDT/PDI. This tutorial represents a comprehensive collection of operative instructions, by which, based on photochemical and photophysical properties of a PS, its uptake into cells, the intracellular localization and photodynamic action in both tumor cells and microorganisms novel photoactive molecules may be characterized for their suitability for PDT/PDI. Furthermore, it shall stimulate the efforts to expand the convincing benefits of photodynamic therapy and photodynamic inactivation within both established and new fields of applications and motivate scientists of all disciplines to get involved in photodynamic research.

Renal cell neoplasias: reversion-inducing cysteine-rich protein with Kazal motifs discriminates tumor subtypes, while extracellular matrix metalloproteinase inducer indicates prognosis

BackgroundMatrix metalloproteinases can promote invasion and metastasis, which are very frequent in renal cell carcinoma even at the time of diagnosis. Knowing the reversion-inducing cysteine-rich protein with Kazal motifs (RECK) as an inhibitor of matrix metalloproteinases and the extracellular matrix metalloproteinase inducer (EMMPRIN) protein as inducer, we aimed to determine their expression, localization and possible antagonistic action in the pathogenesis and progression of renal cell tumors in a retrospective study.MethodsTumor and adjacent normal tissues of 395 nephrectomized patients were immunostained for RECK and EMMPRIN on a tissue microarray.ResultsRECK strongly decreased in renal cell carcinoma compared to normal counterparts (Wilcoxon signed rank test, P < 0.001), and it discriminated tumor entities showing the highest expression in oncocytomas. EMMPRIN, however, could be significantly correlated to pT stage and Fuhrman grading (Spearman’s correlation coefficient rs = 0.289 and rs = 0.382, respectively). Higher expression of EMMPRIN was associated with decreased overall survival in Kaplan-Meier analysis (P < 0.001), and the EMMPRIN level could independently predict survival for cases without metastasis and involvement of lymph nodes. Decreased RECK expression was confirmed by Western blotting in tissue of eight normal/tumor matches of patients after radical nephrectomy, whereas the EMMPRIN pattern appeared to be heterogeneous.ConclusionsWe propose RECK down regulation in renal cell carcinoma to be an early event that facilitates tumor formation and progression. EMMPRIN, however, as a prognostic tumor marker, increases only when aggressiveness is proceeding and could add an additional step to invasive properties of renal cell carcinoma.