Cellular Systems Research Articles

Peroxiredoxin 3 deficiency exacerbates DSS-induced acute colitis via exosomal miR-1260b-mediated barrier disruption and pro-inflammatory signaling.

Peroxiredoxin3 (Prdx3) is an intracellular antioxidant enzyme that is specifically localized in mitochondria and protects against oxidative stress by removing mitochondrial reactive oxygen species (ROS). The intestinal epithelium provides a physical and biochemical barrier that segregates host tissues from commensal bacteria to maintain intestinal homeostasis. An imbalance between the cellular antioxidant defense system and oxidative stress has been implicated in the pathogenesis of inflammatory bowel disease (IBD). However, the role of Prdx3 in the intestinal epithelium under intestinal inflammation has not been elucidated. To investigate the potential role of Prdx3 in intestinal inflammation, we used intestinal epithelial cell (IEC)-specific Prdx3-knockout mice. IEC-specific Prdx3-deficient mice showed more severe colitis phenotypes with greater degrees of body weight loss, colon shortening, barrier disruption, mitochondrial damage, and ROS generation in IECs. Furthermore, exosomal miR-1260b was dramatically increased in Prdx3-knockdown colonic epithelial cells. Mechanistically, Prdx3 deficiency promoted intestinal barrier disruption and inflammation via P38-MAPK/NFκB signaling. this is the first study to report the protective role of Prdx3 in acute colitis using IEC-specific conditional knockout mice. our study sheds light on the role of exosome-loaded miRNAs, particularly miR-1260b, in IBD. targeting miR-1260b or modulating exosome-mediated intercellular communication may hold promise as potential therapeutic strategies for managing IBD and restoring intestinal barrier integrity.

Dynamic SNR, Spectral Efficiency, and Rate Characterization in 5G/6G mmWave/sub-THz Systems with Macro- and Micro-Mobilities

The performance of 5G/6G cellular systems operating in millimeter wave (mmWave, 30–100 GHz) and sub-terahertz (sub-THz, 100–300 GHz) bands is conventionally assessed by utilizing the static distributions of user locations. The rationale is that the use of the beam tracking procedure allows for keeping the beams of a base station (BS) and user equipment (UE) aligned at all times. However, by introducing 3GPP Reduced Capability (RedCap) UEs utilizing the Radio Resource Management (RRM) Relaxation procedure, this may no longer be the case, as UEs are allowed to skip synchronization signal blocks (SSB) to improve energy efficiency. Thus, to characterize the performance of such UEs, methods explicitly accounting for UE mobility are needed. In this paper, we will utilize the tools of the stochastic geometry and random walk theory to derive signal-to-noise ratio (SNR), spectral efficiency, and rate as an explicit function of time by accounting for mmWave/sub-THZ specifics, including realistic directional antenna radiation patterns and micro- and macro-mobilities causing dynamic antenna misalignment. Different from other studies in the field that consider time-averaged performance measures, these metrics are obtained as an explicit function of time. Our numerical results illustrate that the macro-mobility specifies the overall trend of the time-dependent spectral efficiency, while local dynamics at 1–3 s scales are mainly governed by micro-mobility. The difference between spectral efficiency corresponding to perfectly synchronized UE and BS antennas and time-dependent spectral efficiency in a completely desynchronized system is rather negligible for realistic cell coverages and stays within approximately 5–10% for a wide range of system parameters. These conclusions are not affected by the utilized antenna array at the BS side. However, accounting for realistic radiation patterns is critical for a time-dependent performance analysis of 5G/6G mmWave/sub-THz systems.

IMMUNOLOGICAL CRITERIA OF THE EFFECTIVENESS OF IMMUNOPREVENTIVE OF THE NON-SPECIFIC IMMUNOMODULATOR BIVEL AMONG CONTACTED CHILDREN

The aim of the study - to study the feasibility of using the natural immunomodulator BIVEL (conditionally called BI-V) as a nonspecific immunoprevention of tuberculosis (TB) among contacted children from the focies of chemodrug-resistant tuberculosis infection on the basis of clinical and immunological researches. Research metods. The object of study was 120 contacted from multidrug-resistant tuberculosis infection (FsMDR-TBI) including 75 children and 45 adolescents. The first contact group included 95 children/adolescents who did not receive BI-V and the second one ‒ 25 infected children/adolescents who received BI-V. Immunological studies determining the state of the phagocytic reactivity of immunity (phagocytic number and index, testes redox activity of neutrophils and non-enzymatic cationic lysosomal proteins of granulocytic leukocytes; cellular (CD3+, CD56+, CD3+HLA-DR+, CD4+, CD8+, CD4+/CD8+, CD4+45RA, CD16/56+) and humoral (CD19+, IgA, IgM, IgG, CIC) immunity; interleukins (TNF-α, IL-6, IL-10) and specific immunity (tuberculin diagnostics, Quantiferon test). Statistical analysis of the results obtained based on the software package Excel Results and discussion. On the background of non-specific preventive with the BI-V immunomodulator among contact infected children, normalization of blood phagocytic activity indicators was noted in the form of an increase in phagocytic number, phagocytic index, non-enzymatic cationic lysosomal proteins of granulocytic leukocytes and a decrease in HST test compared to children who had not yet received preventive BI-V. In infected children/adolescents from FsMDR-TBI, while maintaining normal values of CD3+, CD3+CD4+, CD3+CD8+, insignificant functional disorders of the cell response were revealed at the level of immunoregulatory processes due to the dominance of suppressor-cytotoxic reactions were revealed (decrease by 1.3 times IRI CD3+CD4+/CD3+CD8+, p<0.05, relative to donors), balance shift in the regulatory system of pro- and anti-inflammatory cytokines towards pro-inflammatory cytokines (increase by 2.0 times TNF-α/IL-10, p<0.01, relative to normal). The existing deviations in the regulatory system and the cellular response system disappeared after the completion of the autumn-spring BI-V course. Among the children from FsMDR-TBI who took a BI-V preventive course 8% people fell ill with various forms of primary pulmonary TB, among the children who BI-V was not prescribed ‒ 22.1%, p<0.05 during the 4-year observation. The maximum TB level occurred in the first two years of observation in both groups. Conclusions. The results of the appointment of a non-specific immunomodulator BI-V confirmed the feasibility of using this immunomodulator for contacted children and adolescents from FsMDR-TBI.

Modern approaches to the creation of 2D and 3D cellular models for the study of lung fibrosis

Lung fibrosis is a consequence of many influences leading to damage to lung tissue and the development of subsequent inflammation. Fibrosis is an overgrowth of connective tissue, which can lead to a violation of the architectonics of the lungs and reduce their functionality up to a fatal outcome. At the same time, the mechanisms underlying fibrogenesis are currently insufficiently studied. In this regard, the task of studying them does not lose its relevance, and its solution requires the development of models of lung fibrosis that can reflect all the key processes of fibrogenesis.The in vivo model using animals has multiple undeniable advantages, but at the same time it has strict ethical limitations and does not reflect all the mechanisms of lung fibrosis inherent in the human body. At the same time, in vitro research, scientists can afford to use biomaterials not only of animals, but also of humans, and build cellular systems based on them — from 2D to 3D models. Modeling of pulmonary fibrosis is mainly based on the use of the main types of cells involved in the development of pulmonary fibrosis, such as myofibroblasts, fibroblasts, alveolocytes and others. Some models are also based on a specific fibrosis-associated extracellular matrix and further study of the interaction of cells with each other and with the matrix. It should be borne in mind that different models display individual nuances of the native processes of lung fibrogenesis, which requires the research community to use a wide range of models. Taking into account the multifactorial pathogenesis of pulmonary fibrosis, it is important to understand the totality of the processes taking place in order to obtain the completeness of the real picture, close to the picture in vivo, and therefore the multicomponence of models is important. This review focuses on the analysis of various models of lung fibrosis in vitro in two-dimensional and three-dimensional systems, shows approaches to their creation, key differences, main advantages and disadvantages of models, both particular and general.

An investigation on the recurrent function of the Pythagorean fuzzy cellular topological dynamical system

This study is about Pythagorean fuzzy cellular topological dynamical system which is generated using Pythagorean fuzzy cellular space. A dynamical system receives input for a certain function and performs an iterative procedure for that same function. A continuous function can be employed in a topological dynamical system and the same function is iterated again and again. As it is an iterative process, there is a perspective that the views of every individual may be ambiguous or imprecise. To overcome this uncertainty, Pythagorean fuzzy sets are employed in dynamical system. Fixing a boundary on the Pythagorean fuzzy dynamical system culminates in a Pythagorean fuzzy cellular topological dynamical system. It is shown that the Pythagorean fuzzy cellular space is compact, normal and homeomorphic and it is called the Pythagorean fuzzy cellular topological dynamical system. The Pythagorean fuzzy sets in the Pythagorean fuzzy cellular topological dynamical system are iterated under the action of Pythagorean fuzzy cellular continuous map. Then, the Pythagorean fuzzy orbit* set is obtained. Additionally, it is discussed that the stipulated dynamical system is topologically transitive and different aspects of topological transitivity are investigated.

The new science of sleep: From cells to large-scale societies.

In the past 20 years, more remarkable revelations about sleep and its varied functions have arguably been made than in the previous 200. Building on this swell of recent findings, this essay provides a broad sampling of selected research highlights across genetic, molecular, cellular, and physiological systems within the body, networks within the brain, and large-scale social dynamics. Based on this raft of exciting new discoveries, we have come to realize that sleep, in this moment of its evolution, is very much polyfunctional (rather than monofunctional), yet polyfunctional for reasons we had never previously considered. Moreover, these new polyfunctional insights powerfully reaffirm sleep as a critical biological, and thus health-sustaining, requisite. Indeed, perhaps the only thing more impressive than the unanticipated nature of these newly emerging sleep functions is their striking divergence, from operations of molecular mechanisms inside cells to entire group societal dynamics.

Optimized CRISPR-Based Knockout in BeWo Cells

CRISPR genome editing is a widely used tool to perturb genes of interest within cells and tissues and can be used as a research tool to study the connection between genotypes and cellular phenotypes. Highly efficient genome editing is limited in certain cell types due to low transfection efficiency or single-cell survivability. This is true for BeWo cells, an in vitro model of placental syncytiotrophoblast cell-cell fusion and hormone secretion. Here we describe an optimized and easy-to-use protocol for knockout in BeWo cells using CRISPR Cas9 ribonucleoprotein (RNP) complexes delivered via electroporation. Further, we describe parameters for successful guide RNA design and how to assess genetic knockouts in BeWo cells so that users can apply this technique to their own genes of interest. We provide a positive control for inducing highly efficient knockout of the cell-cell fusion protein Syncytin-2 (ERVFRD-1) and assessing editing efficiency at this locus. We anticipate that efficient RNP-mediated genetic knockouts in BeWo cells will facilitate the study of new genes involved in cell-cell fusion and hormone secretion in this important cellular model system. Furthermore, this strategy of optimized nucleofection and RNP delivery may be of use in other difficult-to-edit trophoblast cells or could be applied to efficiently deliver transgenes to BeWo cells.

The iAAA-mitochondrial protease YME1L1 regulates the degradation of the short-lived mitochondrial transporter SLC25A38.

Mitochondrial transporters facilitate the exchange of diverse metabolic intermediates across the inner mitochondrial membrane, ensuring an adequate supply of substrates and cofactors to support redox and biosynthetic reactions within the mitochondrial matrix. However, the regulatory mechanisms governing the abundance of these transporters, crucial for maintaining metabolic compartmentalization and mitochondrial functions, remain poorly defined. Through analysis of protein half-life data and mRNA-protein correlations, we identified SLC25A38, a mitochondrial glycine transporter, as a short- lived protein with a half-life of 4 hours under steady-state conditions. Pharmacological inhibition and genetic depletion of various cellular proteolytic systems revealed that SLC25A38 is rapidly degraded by the iAAA-mitochondrial protease YME1L1. Depolarization of the mitochondrial membrane potential induced by the mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrozone prevented the degradation of SLC25A38. This dual regulation of SLC25A38 abundance by YME1L1 and mitochondrial membrane potential suggests a link between SLC25A38 turnover, the integrity of the inner mitochondrial membrane, and electron transport chain function. These findings open avenues for investigating whether mitochondrial glycine import coordinates with mitochondrial bioenergetics.

High throughput cell mechanotyping of cell response to cytoskeletal modulations using a microfluidic cell deformation system.

Cellular mechanical properties influence cellular functions across pathological and physiological systems. The observation of these mechanical properties is limited in part by methods with a low throughput of acquisition or with low accessibility. To overcome these limitations, we have designed, developed, validated, and optimized a microfluidic cellular deformation system (MCDS) capable of mechanotyping suspended cells on a population level at a high throughput rate of ∼300 cells pers second. The MCDS provides researchers with a viable method for efficiently quantifying cellular mechanical properties towards defining prognostic implications of mechanical changes in pathology or screening drugs to modulate cytoskeletal integrity.

Statistical analysis in cellular systems for channel capacity improvement with dynamic pilots across different angles users

Accurate channel state information (CSI) is crucial for optimizing wireless communication systems. In scenarios with varying user-to-base station angles, the angle-dependent coherence time impacts conventional pilot strategies. Due to small angles, the coherence time of the user decreases dramatically because of doppler shift, which causes an increase in the number of pilots. We introduces an innovative sub-block design approach for systems with different user angles. This method harmonizes coherence time of high and low-angle users, while maintaining a constant pilot count. This not only improves spectral efficiency but also ensures accurate channel estimation. Through simulations, we demonstrate the effectiveness of our approach in enhancing both spectral efficiency upt to 10%\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$10 \\%$$\\end{document} and CSI precision. This breakthrough contributes to the advancement of channel estimation techniques in scenarios with angle-dependent coherence time, offering practical benefits to wireless communication systems.

Abstract B016: Discovering novel synthetic lethal relationships with large-scale cellular simulations

Abstract Synthetic Lethality (SL) is a compelling example of a large combinatorial space, with the number of (order-independent) pairwise combinations of human genes totaling approximately 400 million. When further considering higher-order combinations beyond pairs i.e. additional biomarkers that modulate the the efficacy of an SL pair, this space grows exponentially larger still. Understanding these higher-order combinations is crucial for the discovery of synthetic lethal pairs with better defined therapeutic windows and improved segmentation in clinical trials. As the size of this combinatorial space is far greater than can be searched by existing screening technologies, novel approaches are required to efficiently search this space and prioritize higher-order candidate SL combinations for screening. DeepOrigin is developing large-scale dynamical models of cellular systems to drive the in silico discovery of novel therapeutics across a range of diseases. These models can be simulated efficiently and in parallel, and are therefore ideally suited for searching large combinatorial spaces. We have applied our proprietary Cellular Simulation Pipeline to the problem of identifying higher-order combinations in Synthetic Lethality, so far predicting hundreds of novel synthetic lethal pairs. These pairs are currently being validated in vitro, and we present a selection of these results that demonstrate the utility of this approach. This approach could provide both novel therapeutic targets while providing additional stratification criteria for increased clinical study success. Citation Format: Oliver Purcell, Paul Lang, James Komianos, Nimi Vashi. Discovering novel synthetic lethal relationships with large-scale cellular simulations [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr B016.

Parameter Estimation of Cellular Communication Systems Models in Computational MATLAB Environment: A Systematic Solver-based Numerical Optimization Approaches

Parameter Estimation of Cellular Communication Systems Models in Computational MATLAB Environment: A Systematic Solver-based Numerical Optimization Approaches

A Perspective on the Characterization of Early Neural Progenitor Cell-Derived Extracellular Vesicles for Targeted Delivery to Neuroblastoma Cells.

As an element of the cellular signaling systems, extracellular vesicles (EVs) exhibit many desirable traits for usage as targeted delivery vehicles. When administered, EVs cause little to no toxic or immune response, stay in circulation for longer periods compared to synthetic carriers, preferentially accumulate in tissues that are the same or similar to their cell-of-origin and can pass through the blood-brain barrier. Combined, these traits make neural EVs a particularly promising tool for delivering drugs to the brain. This study aims to combine tissue and EVs engineering to prepare neural differentiated cells derived EVs that exhibit neural properties, to develop an effective, tissue-homing drug and gene delivery platform for the brain. Early neural differentiated cell-derived EVs were produced with neural characteristics from neural differentiated human neonatal dermal fibroblasts. The EVs carried key neural proteins such as Nestin, Sox2 and Doublecortin. The cellular uptake of early neural differentiated cell-derived EVs was higher compared to non-neural EVs during in vitro uptake assays on neuroblastoma cells. Moreover, eND-EVs were significantly decreased the viability of neuroblastoma cells. In conclusion, this study revealed that early neural differentiated cell-derived EVs have potential as a promising drug carrier for the treatment of various neural disorders.

Lipid unsaturation promotes BAX and BAK pore activity during apoptosis

BAX and BAK are proapoptotic members of the BCL2 family that directly mediate mitochondrial outer membrane permeabilition (MOMP), a central step in apoptosis execution. However, the molecular architecture of the mitochondrial apoptotic pore remains a key open question and especially little is known about the contribution of lipids to MOMP. By performing a comparative lipidomics analysis of the proximal membrane environment of BAK isolated in lipid nanodiscs, we find a significant enrichment of unsaturated species nearby BAK and BAX in apoptotic conditions. We then demonstrate that unsaturated lipids promote BAX pore activity in model membranes, isolated mitochondria and cellular systems, which is further supported by molecular dynamics simulations. Accordingly, the fatty acid desaturase FADS2 not only enhances apoptosis sensitivity, but also the activation of the cGAS/STING pathway downstream mtDNA release. The correlation of FADS2 levels with the sensitization to apoptosis of different lung and kidney cancer cell lines by co-treatment with unsaturated fatty acids supports the relevance of our findings. Altogether, our work provides an insight on how local lipid environment affects BAX and BAK function during apoptosis.

Simultaneous consideration of time and cost impacts of machine failures on cellular manufacturing systems

Cellular manufacturing systems (CMS) are essential for achieving efficient production processes, and their success relies on effective cell formation and layout design. This research paper presents a novel nonlinear mathematical programming model that employs the rectilinear distance notion to define the layout within a continuous space. The proposed model incorporates the stochastic nature of machine failures, considering the unreliability with the inclusion of a stochastic time between failures. With a bi-objective approach, the model aims to minimize inter and intra-cell movements of parts, as well as the associated costs related to exceptional elements (EEs), cell reconfigurations, and machine failures. To optimize the proposed model, several multi-objective meta-heuristic algorithms, including the multi-objective particle swarm optimization (MOPSO), multi-objective taboo search (MOTS), and non-dominated sorting genetic algorithm (NSGA-II), are introduced. The effectiveness of these algorithms is validated through numerical instances and a real case study. The results indicate that the MOPSO algorithm exhibits superior performance in optimizing various multi-objective criteria. The presented mathematical model and algorithms provide valuable tools for manufacturers to optimize their CMS, resulting in reduced costs, enhanced production efficiency, and increased competitiveness. By considering the simultaneous effects of time and cost associated with machine failures, this research offers practical insights and solutions for improving the performance of cellular manufacturing systems.

Autophagy Behavior under Local Hypothermia in Myocardiocytes Injury.

Hypothermia and autophagy are critical regulators of cell homeostasis by regulating intra and intercellular cell communication. Myocardiocyte cryotherapy poses multiple cellular and subcellular effects on the injured cell, including upregulation of autophagy. Autophagy plays a crucial role in modifying cell metabolism by regulating downregulation, reducing reactive oxygen species production, and improving the natural cellular antioxidant defense system. Reduction of reactive oxygen species production and improving natural cellular antioxidant defense system. Therapeutic hypothermia ranges from 32-34°C in terms of local myocardiocyte cooling. Hypothermia induces autophagy by phosphorylating the Akt signaling pathway. Hypothermia has a more therapeutic effect when applied at the beginning of reperfusion rather than in the beginning of ischemia. Moderate hypothermia with 33°C poses most therapeutic effect by viability maintaining and reduction of reactive oxygen species release. Application of local hypothermia to myocardiocytes can be applied to infarcted myocardiocytes, anginal and to the cardiomyopathies.

Associations of T-cell fitness prior to B-cell maturation antigen (BCMA)–targeted chimeric antigen receptor T-cell (CART) and bispecific T-cell engager (BiTE) therapies and efficacy/toxicity in relapsed/refractory multiple myeloma (RRMM).

7549 Background: While CART and BiTE have led to unprecedented responses in RRMM, some patients (pts) do not respond or have short-lived responses. Currently no predictive markers exist to identify these pts. This study explored pretreatment T-cell fitness and efficacy/toxicity in RRMM using a novel single-cell secretome analysis. We hypothesized that pretreatment Polyfunctional Strength Index (PSI) may predict efficacy to BCMA-directed T-cell therapies. Methods: We included 14 RRMM pts treated with idecabtagene vicleucel or teclistamab at Yale Cancer Center with ≥6 mos post-treatment follow-up. Peripheral blood prior to treatment was frozen and then PBMC’s thawed for analysis. PSI, a metric for T-cell fitness combining polyfunctional T-cells % with the intensity of secreted cytokines, was obtained using the IsoPlexis’ Single-Cell Secretome Platform. The overall PSI was an average of CD4+ and CD8+ PSIs. Response was assessed by the International Myeloma Working Group criteria and response duration was defined as time from response to disease progression. Responder (R) was defined as ≥very good partial response for ≥6 mos. Non-responder (NR) was defined as stable or progressive disease ≤3 mos. Cytokine release syndrome (CRS) and immune-effector cell associated neurotoxicity syndrome (ICANS) were graded using the American Society for Transplantation & Cellular Therapy system. Statistics were performed with Mann-Whitney U test using GraphPad PRISM v.9. Results: There were 7 pts in R group (2 BiTE & 5 CART) and 7 pts in NR group (3 BiTE & 4 CART). Median follow-up time was 13.5 mos(range, 7-27). Median age at treatment was 64 yrs in R and 63 yrs in NR. Extramedullary disease (EM) was present in 14.3%(n=1) in R and 71.4%(n=5) in NR. High-risk cytogenetics, defined as del17p, t(4;14), t(14;16), t(14;20), 1q gain/amplification and del1p, were seen in 42.9%(n=3) in R and 85.7%(n=6) in NR. Median prior lines of therapy was 6(range, 4-9) in R and 8(range, 4-10) in NR. CRS/ICANS occurred 85.7%(n=6) in R and 28.6%(n=2) in NR. Overall PSI was 184 in R and 91 in NR(p=0.1649). CD4+ PSI was 160 in R and 75 in NR(p=0.1649). CD8+ PSI was 207 in R and 108 in NR(p=0.1981). Overall PSI was 143 in CRS/ICANS and 130 in no CRS/ICANS(p=0.7546). Conclusions: Overall PSI, CD4+ PSI and CD8+ PSI were 1.9-2.1 times higher in R compared to NR and overall PSI was slightly higher in CRS/ICANS compared to no CRS/ICANS though the difference was not statistically significant. One limitation was a small sample size and thus testing PSI in a larger cohort might yield statistically significant results. The NR group had more high-risk cytogenetics and higher EM. One confounder could be that measuring peripheral T-cell fitness may not be sufficient to predict response in EM where spatial determinants of T-cell influx play a role.

Peak-to-average power ratio minimization and complexity reduction in MIMO-OFDM systems using spatial circular shifting and temporal interleaving method

Multiple-input multiple-output orthogonal frequency division multiplexing(MIMO-OFDM) technological support for the simultaneous and frequent access by a large number of users to radio resources. For 5G cellular systems, this exhaust is not enough to provide physical layer services. An appropriate Peak-to-average power ratio (PAPR) minimization principle, which maximizes data capacity and channel utility, has been used to address this issue. In this paper, mainly focus on minimize the high PAPR of the candidate sequence of the OFDM sub-block using modified enhancement asymmetric arithmetic coding scheme (M-EAAC). According to this, circular shifting of the candidate sequence is established in the spatial circular shifting and temporal interleaving (SCS-TI) form to generated different set of conjugated phases which is multiplied with candidate sequence. Then, the transmitting antenna is identified the best lowest PAPR of the candidate sequence is chosen for entire OFDM data transmission. The simulation results conveys that the proposed SCS-TI method provide acceptable improvement in the PAPR reduction as compared with conventional selective mapping(SLM)and pseudo-random SLM(PR-SLM). Moreover, the complexity evaluation which ensure the proposed method provides better improvement at three important stages includes inverse fast Fourier transform (IFFT) operation, optimization process, and PAPR calculation at each candidate sequence.

Human Umbilical Vein Endothelial Cells as a Versatile Cellular Model System in Diverse Experimental Paradigms: An Ultrastructural Perspective.

Human umbilical vein endothelial cells (HUVECs) are primary cells isolated from the vein of an umbilical cord, extensively used in cardiovascular studies and medical research. These cells, retaining the characteristics of endothelial cells in vivo, serve as a valuable cellular model system for understanding vascular biology, endothelial dysfunction, pathophysiology of diseases such as atherosclerosis, and responses to different drugs or treatments. Transmission electron microscopy (TEM) has been a cornerstone in revealing the detailed architecture of multiple cellular model systems including HUVECs, allowing researchers to visualize subcellular organelles, membrane structures, and cytoskeletal elements. Among them, the endoplasmic reticulum, Golgi apparatus, mitochondria, and nucleus can be meticulously examined to recognize alterations indicative of cellular responses to various stimuli. Importantly, Weibel-Palade bodies are characteristic secretory organelles found in HUVECs, which can be easily distinguished in the TEM. These distinctive structures also dynamically react to different factors through regulated exocytosis, resulting in complete or selective release of their contents. This detailed review summarizes the ultrastructural features of HUVECs and highlights the utility of TEM as a pivotal tool for analyzing HUVECs in diverse research frameworks, contributing valuable insights into the comprehension of HUVEC behavior and enriching our knowledge into the complexity of vascular biology.

Targeted Therapy of Tumors and Cancer Stem Cells based on Oxidant-Regulated Redox Pathway and its Mechanism.

A malignant tumor is a frequent and common disease that severely threatens human health. Many mechanisms, such as cell signaling pathway, anti-apoptosis mechanism, cell stemness, metabolism, and cell phenotype, have been studied to explain the reasons for chemotherapy, radioresistance, and tumor recurrences in antitumor treatment. Cancer stem cells (CSCs) are important tumor cell subclasses that can potentially organize and regulate stem cell properties. Growing evidence suggests that CSCs can initiate tumors and constitute a significant factor in metastasis, recurrence, and treatment resistance. The inability to completely target and remove CSCs is a considerable obstacle in tumor treatment. Therefore, drugs and therapeutic strategies that can effectively intervene with CSCs are essential for the treatment of different tumor types. However, the current strategies and efficacy of targeted elimination of CSCs are very limited. Oxidative stress has been recognized to play a crucial role in cancer pathophysiology. Moreover, reactive oxygen species (ROS) production and imbalance of the built-in cellular antioxidant defense system are hallmarks of tumor and cancer etiology. The current paper will focus on the regulation and mechanism behind oxidative stress in tumors and cancer stem cells and its tumor therapy applications. Additionally, the article discusses the role of CSCs in causing tumor treatment resistance and recurrence based on a redox perspective. The study also emphasizes that targeted modulation of oxidative stress in CSCs has great potential in tumor therapy, providing novel prospects for tumor therapy.