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The theme of the 2022 symposium was 'Cell Diversity in the Cardiovascular System, cell-autonomous and cell-cell signalling'. Keywords: cardiovascular physiology; cell diversity; ion channels; vascular smooth muscle EN cardiovascular physiology cell diversity ion channels vascular smooth muscle 2543 2544 2 07/04/23 20230701 NES 230701 This paper is based on the most recent UC Davis Cardiovascular Research Symposium on Systems Approach to Understanding Cardiovascular Disease and Arrhythmia. Cardiovascular physiology, ion channels, vascular smooth muscle, cell diversity. [Extracted from the article]

This essay looks at six APS classic papers published by D. H. Hubel and T. N. Wiesel that first identified a developmental critical period for environment influenced receptive field plasticity in the visual pathway. These classic papers are freely available online. These are listed here, in chronological order. WIESEL TN, HUBEL DH: Effects of visual deprivation on morphology and physiology of cells in the cat's lateral geniculate body. J Neurophysiol 26: 978–993, 1963 (http://jn.physiology.org/cgi/reprint/26/6/978). HUBEL DH, WIESEL TN: Receptive fields of cells in striate cortex of very young, visually inexperienced kittens. J Neurophysiol 26: 994–1002, 1963 (http://jn.physiology.org/cgi/reprint/26/6/994). WIESEL TN, HUBEL DH: Single-cell responses in striate cortex of kittens deprived of vision in one eye. J Neurophysiol 26: 1003–1017, 1963 (http://jn.physiology.org/cgi/reprint/26/6/1003). WIESEL TN, HUBEL DH: Comparison of the effects of unilateral and bilateral eye closure on cortical unit responses in kittens. J Neurophysiol 28: 1029–1040, 1965 (http://jn.physiology.org/cgi/reprint/28/6/1029). HUBEL DH, WIESEL TN: Binocular interaction in striate cortex of kittens reared with artificial squint. J Neurophysiol 28: 1041–1059, 1965 (http://jn.physiology.org/cgi/reprint/28/6/1041). WIESEL TN, HUBEL DH: Extent of recovery from the effects of visual deprivation in kittens. J Neurophysiol 28: 1060–1072, 1965 (http://jn.physiology.org/cgi/reprint/28/6/1060). [ABSTRACT FROM AUTHOR]

Ca2+ imaging is the most frequently used technique to study glial cell physiology. While chemical Ca2+ indicators served to visualize and measure changes in glial cell cytosolic Ca2+ concentration for several decades, genetically encoded Ca2+ indicators (GECIs) have become state of the art in recent years. Great improvements have been made since the development of the first GECI and a large number of GECIs with different physical properties exist, rendering it difficult to select the optimal Ca2+ indicator. This review discusses some of the most frequently used GECIs and their suitability for glial cell research. [ABSTRACT FROM AUTHOR]

This document is an editorial published in the journal Frontiers in Cell & Developmental Biology. The editorial discusses the topic of metabolic modulation of cellular function. It highlights the role of metabolites in regulating cell function, fate, and structure, and how metabolic changes can impact cell signaling and cell death pathways. The editorial also explores the connection between metabolic reprogramming and cell fate determination, diseases caused by metabolic dysfunction, drug discovery, embryonal development, aging, and the impact of environmental stressors on metabolic diseases. The papers presented in this Research Topic demonstrate the importance of understanding the metabolic machinery in deciphering biological processes in health and disease. [Extracted from the article]

Simple Summary: In spontaneous tumor regression, tumors shrink and disappear without conventional treatments. This phenomenon challenges the view that cancer is an irreversible genetic disease and that the only treatment option is to kill cancer cells or surgically remove them. In tumor reversion, cancer cells have been shown to return to normal cells when they are transplanted into a normal cellular environment. Additionally, people consuming a Western diet ingest excessive amounts of dietary phosphate, and a dysregulated oversupply of phosphate can be transported into cells, stimulating the cellular growth that forms tumors. Based on reviewed evidence, this paper proposes that reducing excessive dietary phosphate potentially activates tumor regression and reversion, as components of cancer cells are self-digested. Furthermore, fevers and fasting-mimicking diets are associated with tumor regression, which also may be initiated by reduced phosphate intake. Studies are needed to test dietary phosphate reduction in tumor regression and reversion to improve cancer patient survival. Tumors that spontaneously shrink from unknown causes in tumor regression, and that return to normal cells in tumor reversion, are phenomena with the potential to contribute new knowledge and novel therapies for cancer patient survival. Tumorigenesis is associated with dysregulated phosphate metabolism and an increased transport of phosphate into tumor cells, potentially mediated by phosphate overload from excessive dietary phosphate intake, a significant problem in Western societies. This paper proposes that reduced dietary phosphate overload and reregulated phosphate metabolism may reverse an imbalance of kinases and phosphatases in cell signaling and cellular proliferation, thereby activating autophagy in tumor regression and reversion. Dietary phosphate can also be reduced by sickness-associated anorexia, fasting-mimicking diets, and other diets low in phosphate, all of which have been associated with tumor regression. Tumor reversion has also been demonstrated by transplanting cancer cells into a healthy microenvironment, plausibly associated with normal cellular phosphate concentrations. Evidence also suggests that the sequestration and containment of excessive phosphate within encapsulated tumors is protective in cancer patients, preventing the release of potentially lethal amounts of phosphate into the general circulation. Reducing dietary phosphate overload has the potential to provide a novel, safe, and effective reversion therapy for cancer patients, and further research is warranted. [ABSTRACT FROM AUTHOR]

The analysis of cells frozen within the International Space Station (ISS) will provide crucial insights into the impact of the space environment on cellular functions and properties. The objective of this study was to develop a method for cryopreserving blood cells under the specific constraints of the ISS. In a ground experiment, mouse blood was directly mixed with a cryoprotectant and gradually frozen at −80 °C. Thawing the frozen blood sample resulted in the successful recovery of viable mononuclear cells when using a mixed solution of dimethylsulfoxide and hydroxyethyl starch as a cryoprotectant. In addition, we developed new freezing cases to minimize storage space utilization within the ISS freezer. Finally, we confirmed the recovery of major mononuclear immune cell subsets from the cryopreserved blood cells through a high dimensional analysis of flow cytometric data using 13 cell surface markers. Consequently, this ground study lays the foundation for the cryopreservation of viable blood cells on the ISS, enabling their analysis upon return to Earth. The application of this method in ISS studies will contribute to understanding the impact of space environments on human cells. Moreover, this method may find application in the cryopreservation of blood cells in situations where research facilities are inadequate. [ABSTRACT FROM AUTHOR]

Simple Summary: The present review was performed in order to provide a comprehensive overview of the existing literature concerning the applications of positron emission tomography (PET) radiomics in lung cancer patients candidates or those currently undergoing immunotherapy. Fifteen papers were included, thirteen were qualified as using conventional radiomics approaches, and two used deep learning radiomics. Different settings were analyzed, from the utility of radiomics as an additional tool for predicting the expression of PD-L1 or the tumor microenvironment, to the utility of artificial intelligence in evaluating the response to immunotherapy. Although radiomics seems promising in these fields, too limited data are now available. Indeed, the first limitation is the low amount of data, heterogeneity in the provided information, the still limited experience and also the small amount of expertise in this field. Therefore, radiomics is still far from to be considered for daily routine clinical practice, although some additional efforts are required for the next future, mainly in patients scheduled or undergoing immunotherapy. The aim of this review is to provide a comprehensive overview of the existing literature concerning the applications of positron emission tomography (PET) radiomics in lung cancer patient candidates or those undergoing immunotherapy. Materials and Methods: A systematic review was conducted on databases and web sources. English-language original articles were considered. The title and abstract were independently reviewed to evaluate study inclusion. Duplicate, out-of-topic, and review papers, or editorials, articles, and letters to editors were excluded. For each study, the radiomics analysis was assessed based on the radiomics quality score (RQS 2.0). The review was registered on the PROSPERO database with the number CRD42023402302. Results: Fifteen papers were included, thirteen were qualified as using conventional radiomics approaches, and two used deep learning radiomics. The content of each study was different; indeed, seven papers investigated the potential ability of radiomics to predict PD-L1 expression and tumor microenvironment before starting immunotherapy. Moreover, two evaluated the prediction of response, and four investigated the utility of radiomics to predict the response to immunotherapy. Finally, two papers investigated the prediction of adverse events due to immunotherapy. Conclusions: Radiomics is promising for the evaluation of TME and for the prediction of response to immunotherapy, but some limitations should be overcome. [ABSTRACT FROM AUTHOR]

Protein–drug interactions are crucial for understanding drug delivery and cell functions. Jacalin is a suitable molecule for such targeting, as it specifically recognizes the tumor-associated Thomsen–Friedenreich (TF) antigen that is expressed on the glycosylated proteins in cancer cells. The present paper describes the interaction of curcumin and jacalin, a possible carrier molecule for the delivery of antitumor drugs due to its ability to recognize tumor cells. Our results have shown that both steady-state fluorescence and fluorescent labelling of jacalin are two reliable methods to determine jacalin-curcumin interactions. The affinity of jacalin for curcumin is consistently within the micromolar range (using fluorescence and microscale thermophoresis) showing high-affinity binding of the complex. In vitro experiments on triple-negative breast cancer MDA-MB-231 cells indicated inhibition of cell growth after treating with the jacalin-curcumin complex for 48 h. The cell survival fraction was significantly reduced to 50% after combined treatment. In this paper, we report for the first time about the jacalin-curcumin interaction. We quantified this unique biomolecular interaction and gathered additional information on the binding event. We observed that the jacalin-curcumin complex inhibits the proliferation of the triple-negative breast cancer MDA-MB-231 cells. [ABSTRACT FROM AUTHOR]

Background: Lysine glutarylation (Kglu) is one of the most important Post-translational modifications (PTMs), which plays significant roles in various cellular functions, including metabolism, mitochondrial processes, and translation. Therefore, accurate identification of the Kglu site is important for elucidating protein molecular function. Due to the time-consuming and expensive limitations of traditional biological experiments, computational-based Kglu site prediction research is gaining more and more attention. Results: In this paper, we proposed GBDT_KgluSite, a novel Kglu site prediction model based on GBDT and appropriate feature combinations, which achieved satisfactory performance. Specifically, seven features including sequence-based features, physicochemical property-based features, structural-based features, and evolutionary-derived features were used to characterize proteins. NearMiss-3 and Elastic Net were applied to address data imbalance and feature redundancy issues, respectively. The experimental results show that GBDT_KgluSite has good robustness and generalization ability, with accuracy and AUC values of 93.73%, and 98.14% on five-fold cross-validation as well as 90.11%, and 96.75% on the independent test dataset, respectively. Conclusion: GBDT_KgluSite is an effective computational method for identifying Kglu sites in protein sequences. It has good stability and generalization ability and could be useful for the identification of new Kglu sites in the future. The relevant code and dataset are available at https://github.com/flyinsky6/GBDT_KgluSite. [ABSTRACT FROM AUTHOR]

Simple Summary: The field of cell culture technology involves the cultivation of cells in a controlled environment, mimicking the natural conditions found in living organisms. This process is performed on a large scale, utilizing a specially designed culture medium. The goal is to create either undifferentiated individual cells or multicellular aggregates with minimal differentiation. The present paper offers a comprehensive overview of the advancements and applications of primary cell culture techniques in fish. It places a particular focus on revealing the physiological roles played by fish cells during their in vitro cultivation. Maintaining the functional characteristics of fish cells is of paramount importance, as it is essential for gaining a deeper understanding of the underlying mechanisms governing various physiological processes. To facilitate the use of fish cells in research and practical applications, it is crucial to standardize the separation techniques for these cells and optimize the conditions for their culture. This not only contributes to our knowledge of fish health, disease development, and drug discovery but also drives progress in the aquaculture industry. Fish primary cell culture has emerged as a valuable tool for investigating the physiological roles and responses of various cell types found in fish species. This review aims to provide an overview of the advancements and applications of fish primary cell culture techniques, focusing on the profiling of physiological roles exhibited by fish cells in vitro. Fish primary cell culture involves the isolation and cultivation of cells directly derived from fish tissues, maintaining their functional characteristics and enabling researchers to study their behavior and responses under controlled conditions. Over the years, significant progress has been made in optimizing the culture conditions, establishing standardized protocols, and improving the characterization techniques for fish primary cell cultures. The review highlights the diverse cell types that have been successfully cultured from different fish species, including gonad cells, pituitary cells, muscle cells, hepatocytes, kidney and immune cells, adipocyte cells and myeloid cells, brain cells, primary fin cells, gill cells, and other cells. Each cell type exhibits distinct physiological functions, contributing to vital processes such as metabolism, tissue regeneration, immune response, and toxin metabolism. Furthermore, this paper explores the pivotal role of fish primary cell culture in elucidating the mechanisms underlying various physiological processes. Researchers have utilized fish primary cell cultures to study the effects of environmental factors, toxins, pathogens, and pharmaceutical compounds on cellular functions, providing valuable insights into fish health, disease pathogenesis, and drug development. The paper also discusses the application of fish primary cell cultures in aquaculture research, particularly in investigating fish growth, nutrition, reproduction, and stress responses. By mimicking the in vivo conditions in vitro, primary cell culture has proven instrumental in identifying key factors influencing fish health and performance, thereby contributing to the development of sustainable aquaculture practices. [ABSTRACT FROM AUTHOR]

Simple Summary: Cells continually sense and receive signals from the environment and respond accordingly. Due to biological noise, however, the response is not always as expected. Such a response can induce a different cell fate and may disrupt some cellular functions. In the presence of noise, cells may either mistakenly perceive non-existent signals and act accordingly, or may ignore the actual signals and do nothing. We label these two as false alarm and signal miss events, respectively. In this paper, we consider an important signaling system with one input and two outputs to show how the likelihood of false alarm and signal miss events can be computed, using the experimentally measured joint response of the two outputs of the signaling system. The two system outputs are the nuclear factor κB (NFκB) and the activating transcription factor-2 (ATF-2), whereas the system input is the tumor necrosis factor (TNF). These molecules are highly involved in essential processes such as cell survival, cell death, and viral replication. The introduced methodology and the measured false alarm and miss probabilities using experimental data can model complex cellular decision-making processes and provide insight into how they may contribute to the development of some pathological conditions. A cell constantly receives signals and takes different fates accordingly. Given the uncertainty rendered by signal transduction noise, a cell may incorrectly perceive these signals. It may mistakenly behave as if there is a signal, although there is none, or may miss the presence of a signal that actually exists. In this paper, we consider a signaling system with two outputs, and introduce and develop methods to model and compute key cell decision-making parameters based on the two outputs and in response to the input signal. In the considered system, the tumor necrosis factor (TNF) regulates the two transcription factors, the nuclear factor κB (NFκB) and the activating transcription factor-2 (ATF-2). These two system outputs are involved in important physiological functions such as cell death and survival, viral replication, and pathological conditions, such as autoimmune diseases and different types of cancer. Using the introduced methods, we compute and show what the decision thresholds are, based on the single-cell measured concentration levels of NFκB and ATF-2. We also define and compute the decision error probabilities, i.e., false alarm and miss probabilities, based on the concentration levels of the two outputs. By considering the joint response of the two outputs of the signaling system, one can learn more about complex cellular decision-making processes, the corresponding decision error rates, and their possible involvement in the development of some pathological conditions. [ABSTRACT FROM AUTHOR]

Lignocellulosic materials from municipal solid waste emerge as attractive resources for anaerobic digestion biorefinery. To increase the knowledge required for establishing efficient bioprocesses, dynamics of batch fermentation by the cellulolytic bacterium Ruminiclostridium cellulolyticum were compared using three cellulosic materials, paper handkerchief, cotton discs and Whatman filter paper. Fermentation of paper handkerchief occurred the fastest and resulted in a specific metabolic profile: it resulted in the lowest acetate-to-lactate and acetate-to-ethanol ratios. By shotgun proteomic analyses of paper handkerchief and Whatman paper incubations, 151 proteins with significantly different levels were detected, including 20 of the 65 cellulosomal components, 8 non-cellulosomal CAZymes and 44 distinct extracytoplasmic proteins. Consistent with the specific metabolic profile observed, many enzymes from the central carbon catabolic pathways had higher levels in paper handkerchief incubations. Among the quantified CAZymes and cellulosomal components, 10 endoglucanases mainly from the GH9 families and 7 other cellulosomal subunits had lower levels in paper handkerchief incubations. An in-depth characterization of the materials used showed that the lower levels of endoglucanases in paper handkerchief incubations could hypothetically result from its lower crystallinity index (50%) and degree of polymerization (970). By contrast, the higher hemicellulose rate in paper handkerchief (13.87%) did not result in the enhanced expression of enzyme with xylanase as primary activity, including enzymes from the “xyl-doc” cluster. It suggests the absence, in this material, of molecular structures that specifically lead to xylanase induction. The integrated approach developed in this work shows that subtle differences among cellulosic materials regarding chemical and structural characteristics have significant effects on expressed bacterial functions, in particular the cellulolysis machinery, resulting in different metabolic patterns and degradation dynamics. [ABSTRACT FROM AUTHOR]

This document is a retraction notice from the journal Bioscience Reports regarding an article titled "Long non-coding RNA SNHG14 exerts oncogenic functions in non-small cell lung cancer through acting as a miR-340 sponge." The retraction was initiated by the Editor-in-Chief and the Editorial Board after receiving a notification from a reader about similarities between figures in the paper and papers by different authors. The authors were contacted but did not respond to the concerns raised. Due to the extent of the issues, the article has been retracted. The document also includes copyright information and a link to download the article. [Extracted from the article]

Simple Summary: The rising population of people with obesity has presented an important need for the study of how adipocytes (fat cells) behave and affect biological function. Adipocytes have traditionally been thought to only function as energy storage for the body, an assumption that has led to them being understudied in health sciences. However, recent studies have shown that adipocytes experience forces in vivo, are reactive to mechanical stimuli, and their cell function can be altered by changes to the mechanical microenvironment and, in some cases, contribute to disease. The aim of this review is to summarize recent scientific publications on how adipocytes sense and respond to their mechanical environment, the use of engineered scaffolds to study cell behavior, adipose cell and tissue mechanical properties, and the current state of computational models. The growing obesity epidemic necessitates increased research on adipocyte and adipose tissue function and disease mechanisms that progress obesity. Historically, adipocytes were viewed simply as storage for excess energy. However, recent studies have demonstrated that adipocytes play a critical role in whole-body homeostasis, are involved in cell communication, experience forces in vivo, and respond to mechanical stimuli. Changes to the adipocyte mechanical microenvironment can affect function and, in some cases, contribute to disease. The aim of this review is to summarize the current literature on the mechanobiology of adipocytes. We reviewed over 100 papers on how mechanical stress is sensed by the adipocyte, the effects on cell behavior, and the use of cell culture scaffolds, particularly those with tunable stiffness, to study adipocyte behavior, adipose cell and tissue mechanical properties, and computational models. From our review, we conclude that adipocytes are responsive to mechanical stimuli, cell function and adipogenesis can be dictated by the mechanical environment, the measurement of mechanical properties is highly dependent on testing methods, and current modeling practices use many different approaches to recapitulate the complex behavior of adipocytes and adipose tissue. This review is intended to aid future studies by summarizing the current literature on adipocyte mechanobiology. [ABSTRACT FROM AUTHOR]

Tumor–immune system interactions are very complicated, being highly nonlinear and not well understood. A large number of tumors can potentially weaken the immune system through various mechanisms such as secreting cytokines that suppress the immune response. In this paper, we propose a tumor–immune system interaction model with a nonmonotonic immune response function and adoptive cellular immunotherapy (ACI). The model has a tumor-free equilibrium and at most three tumor-presence equilibria (low, moderate and high ones). The stability of all equilibria is studied by analyzing their characteristic equations. The consideration of nonmonotonic immune response results in a series of bifurcations such as the saddle-node bifurcation, transcritical bifurcation, Hopf bifurcation and Bogdanov–Takens bifurcation. In addition, numerical simulation results show the coexistence of periodic orbits and homoclinic orbits. Interestingly, along with various bifurcations, we also found two bistable scenarios: the coexistence of a stable tumor-free as well as a high-tumor-presence equilibrium and the coexistence of a stable-low as well as a high-tumor-presence equilibrium, which can show symmetric and antisymmetric properties in a range of model parameters and initial cell concentrations. The new findings indicate that under ACI, patients can possibly reach either a stable tumor-free state or a low-tumor-presence state in the presence of nonmonotonic immune response once the immune system is activated. [ABSTRACT FROM AUTHOR]

Introduction: B cells play a pivotal role in adaptive immunity which has been extensively characterised primarily via flow cytometry-based gating strategies. This study addresses the discrepancies between flow cytometry-defined B cell subsets and their high-confidence molecular signatures using single-cell multiomics approaches. Methods: By analysing multi-omics single-cell data from healthy individuals and patients across diseases, we characterised the level and nature of cellular contamination within standard flow cytometric-based gating, resolved some of the ambiguities in the literature surrounding unconventional B cell subsets, and demonstrated the variable effects of flow cytometric-based gating cellular heterogeneity across diseases. Results: We showed that flow cytometric-defined B cell populations are heterogenous, and the composition varies significantly between disease states thus affecting the implications of functional studies performed on these populations. Importantly, this paper draws caution on findings about B cell selection and function of flow cytometric-sorted populations, and their roles in disease. As a solution, we developed a simple tool to identify additional markers that can be used to increase the purity of flow-cytometric gated immune cell populations based on multi-omics data (AlliGateR). Here, we demonstrate that additional non-linear CD20, CD21 and CD24 gating can increase the purity of both naïve and memory populations. Discussion: These findings underscore the need to reconsider B cell subset definitions within the literature and propose leveraging single-cell multi-omics data for refined characterisation. We show that single-cell multi-omics technologies represent a powerful tool to bridge the gap between surface marker-based annotations and the intricate molecular characteristics of B cell subsets. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer Metastasis has been mostly misunderstood and underestimated by the general public regarding cancer deaths. The aims and objectives of the present report was to more fully describe the scientific activities and components that are involved in the malignant cell's fulfillment of the metastatic process and to impress the readership that metastasis is the major cause on all cancer deaths. The paper proceeds to enumerate and describe certain factors that contribute to cancer cell proliferation and subsequent metastasis such as; (a) calcium levels, (b) multiple cell membrane channels, and (c) the chemokine/receptor system. These latter components could serve to provide ideal molecular targets for possible future peptide therapeutic applications in treating cancer patients. Metastasis (Met) largely contributes to the major cause of cancer deaths throughout the world, rather than the growth of the tumor mass itself. The present report brings together several of the pertinent contributors to cancer growth and metastatic processes from an activity standpoint. Such biological activities include the following: (1) cell adherence and detachment; (2) cell-to-cell contact; (3) contact inhibition; (4) the cell interfacing with the extracellular matrix (ECM); (5) tumor cell-to-stroma communication networks; (6) chemotaxis; and (7) cell membrane potential. Moreover, additional biochemical factors that contribute to cancer growth and metastasis have been shown to comprise the following: (a) calcium levels in the extracellular matrix and in intracellular compartments; (b) cation voltage and ATP-regulated potassium channels; (c) selective and non-selective cation channels; and (d) chemokines (cytokines) and their receptors, such as CXCL12 (SDF-1) and its receptor/binding partner, CXCR4. These latter molecular components represent a promising group of an interacting and synchronized set of candidates ideal for peptide therapeutic targeting for cancer growth and metastasis. Such peptides can be obtained from naturally occurring proteins such as alpha-fetoprotein (AFP), an onco-fetal protein and clinical biomarker. [ABSTRACT FROM AUTHOR]

Simple Summary: The word "model" can be used with different meanings and different contexts, like a model student, clay models or a model railway. In some cases, the context can clarify exactly what is meant by "model", but sometimes several meanings of model can be present in one area. For instance, with reference to cancer research, there can be ambiguity for what is meant by model. This paper reviews the use of the word model as related to cancer research and within the specific area of the microenvironment that surrounds a cancer tumour. The review grouped different definitions of model into four categories (model organisms, in vitro models, mathematical models and computational models) and explored what is meant in each case, mentioning the advantages and disadvantages of the different models Next, a quantitative investigation of the scientific publications listed in the database of the United States National Library of Medicine was performed by counting the frequencies of use of these terms, as well as the components of the microenvironments and the organs modelled with these techniques. The Oxford English Dictionary includes 17 definitions for the word "model" as a noun and another 11 as a verb. Therefore, context is necessary to understand the meaning of the word model. For instance, "model railways" refer to replicas of railways and trains at a smaller scale and a "model student" refers to an exemplary individual. In some cases, a specific context, like cancer research, may not be sufficient to provide one specific meaning for model. Even if the context is narrowed, specifically, to research related to the tumour microenvironment, "model" can be understood in a wide variety of ways, from an animal model to a mathematical expression. This paper presents a review of different "models" of the tumour microenvironment, as grouped by different definitions of the word into four categories: model organisms, in vitro models, mathematical models and computational models. Then, the frequencies of different meanings of the word "model" related to the tumour microenvironment are measured from numbers of entries in the MEDLINE database of the United States National Library of Medicine at the National Institutes of Health. The frequencies of the main components of the microenvironment and the organ-related cancers modelled are also assessed quantitatively with specific keywords. Whilst animal models, particularly xenografts and mouse models, are the most commonly used "models", the number of these entries has been slowly decreasing. Mathematical models, as well as prognostic and risk models, follow in frequency, and these have been growing in use. [ABSTRACT FROM AUTHOR]

First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping researchers promote themselves alongside their papers. Anthony Dornan is first author on ‘Compromised junctional integrity phenocopies age)dependent renal dysfunction in Drosophila Snakeskin mutants’, published in JCS. Anthony conducted the research described in this article while at Prof. Julian Dow’s lab at School of Molecular Biosciences, University of Glasgow, UK, where he currently works as a Lab Manager/Research Technician. Anthony’s research focuses on applying molecular genetic techniques, predominantly using the model organism Drosophila and in particular the fly’s Malpighian (renal) tubules, to address fundamental questions in the physiology of cell signalling, transport and stress responses. [ABSTRACT FROM AUTHOR]

A Micro Electro-Mechanical System (MEMS) is a micro-sized mechatronic device based on semiconductor integrated-circuit manufacturing technology. MEMS technology is inherently a very powerful tool for researchers to manipulate and measure the microscopic biological components of biological tissues since their basic constituent units, cells and intracellular microstructures, are also micron or even submicron in size. MEMS technology applied to medicine and life sciences is called Bio-MEMS. Many Bio-MEMS devices and technologies have been developed in recent years, including microfluidic devices for cell culture, manipulation, and measurement, as well as lab-on-a-chip devices for chemical reactions and analyses on MEMS devices. This special issue consists of 13 papers: 1 review article, 1 letter, and 11 research papers. These papers include studies on mechanical stress on cells using MEMS devices, the control of cell functions through microfabrication techniques, cell measurement and in vivo microenvironment simulation using microfluidic devices, and basic research on wearable devices and self-assembling microstructures using MEMS technologies. The editorial committee members are confident that this special issue will make a significant contribution to the further development of Bio-MEMS. We sincerely appreciate the excellent contributions of the authors and the time and effort of the reviewers. We would also like to thank the editorial board of the Journal of Robotics and Mechatronics for their support of this special issue. [ABSTRACT FROM AUTHOR]

Counting and analyzing of blood cells, as well as their subcellular structures, are indispensable for understanding biological processes, studying cell functions, and diagnosing diseases. In this paper, we combine digital holographic microscopy with cell segmentation guided by the Sobel operator using Dice coefficients for automatic threshold selection and aimed to automatic counting and analysis of blood cells in flow and different kinds of cells in the static state. We demonstrate the proposed method with automatic counting and analyzing rat red blood cells (RBCS) flowing in a microfluidic device, extracting quickly and accurately the size, concentration, and dry mass of the sample in a label-free manner. The proposed technique was also demonstrated for automatic segmentation of different cell types, such as COS7 and Siha. This method can help us in blood inspection, providing pathological information in disease diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells are unique from other immune cells in that they can rapidly kill multiple neighboring cells without the need for antigenic pre-sensitization once the cells display surface markers associated with oncogenic transformation. Given the dynamic role of NK cells in tumor surveillance, NK cell-based immunotherapy is rapidly becoming a "new force" in tumor immunotherapy. However, challenges remain in the use of NK cell immunotherapy in the treatment of solid tumors. Many metabolic features of the tumor microenvironment (TME) of solid tumors, including oxygen and nutrient (e.g., glucose, amino acids) deprivation, accumulation of specific metabolites (e.g., lactate, adenosine), and limited availability of signaling molecules that allow for metabolic reorganization, multifactorial shaping of the immune-suppressing TME impairs tumor-infiltrating NK cell function. This becomes a key barrier limiting the success of NK cell immunotherapy in solid tumors. Restoration of endogenous NK cells in the TME or overt transfer of functionally improved NK cells holds great promise in cancer therapy. In this paper, we summarize the metabolic biology of NK cells, discuss the effects of TME on NK cell metabolism and effector functions, and review emerging strategies for targeting metabolism-improved NK cell immunotherapy in the TME to circumvent these barriers to achieve superior efficacy of NK cell immunotherapy. [ABSTRACT FROM AUTHOR]

This paper proposes a new method for assessing the state of charge (SoC) and identifying the types of different lithium-ion cells used in the battery systems of light electric vehicles. A particular challenge in the development of this method was the SoC estimation time, as the method is intended for implementation in the control system of a bicycle charging station, where the state of charge must be determined immediately after the bicycle is plugged in in order to start the charging process as quickly as possible according to the appropriate charging algorithm. The method is based on the identification of the transfer function, i.e., the dynamic response of the battery voltage to the current pulse. In the learning phase of this method, a database of reference transfer functions and corresponding SoCs for a specific type of battery cell is created. The transfer functions are described by coefficients determined through the optimization procedure. The algorithm for estimating the unknown battery cell SoCs is based on the comparison of the measured voltage response with the responses of the reference transfer functions from the database created during the learning process to the same current signal. The comparison is made by calculating the integral of the square error (ISE) between the response of the specific reference transfer function and the measured voltage response of the battery cell. Each transfer function corresponds to a specific SoC and cell type. The specific SoC of the unknown battery is determined by quadratic interpolation of the SoC near the reference point with the smallest ISE for each battery type. The cell type detection algorithm is based on the fact that the integral squared error criterion near the actual SoC for the actual cell type changes less than the squared error criterion for any other battery cell type with the same SoC. An algorithm for estimating the SoC and cell type is described and tested on several different cell types. The relative error between the estimated SoC and the actual SoC was used as a measure of the accuracy of the algorithm, where the actual SoC was calculated using the Coulomb counting method. [ABSTRACT FROM AUTHOR]

This review paper delves into the current body of evidence, offering a thorough analysis of the impact of large-conductance Ca2+-activated K+ (BKCa or BK) channels on the electrical dynamics of the heart. Alterations in the activity of BKCa channels, responsible for the generation of the overall magnitude of Ca2+-activated K+ current at the whole-cell level, occur through allosteric mechanisms. The collaborative interplay between membrane depolarization and heightened intracellular Ca2+ ion concentrations collectively contribute to the activation of BKCa channels. Although fully developed mammalian cardiac cells do not exhibit functional expression of these ion channels, evidence suggests their presence in cardiac fibroblasts that surround and potentially establish close connections with neighboring cardiac cells. When cardiac cells form close associations with fibroblasts, the high single-ion conductance of these channels, approximately ranging from 150 to 250 pS, can result in the random depolarization of the adjacent cardiac cell membranes. While cardiac fibroblasts are typically electrically non-excitable, their prevalence within heart tissue increases, particularly in the context of aging myocardial infarction or atrial fibrillation. This augmented presence of BKCa channels' conductance holds the potential to amplify the excitability of cardiac cell membranes through effective electrical coupling between fibroblasts and cardiomyocytes. In this scenario, this heightened excitability may contribute to the onset of cardiac arrhythmias. Moreover, it is worth noting that the substances influencing the activity of these BKCa channels might influence cardiac electrical activity as well. Taken together, the BKCa channel activity residing in cardiac fibroblasts may contribute to cardiac electrical function occurring in vivo. [ABSTRACT FROM AUTHOR]

Simple Summary: Penile cancer is a rare and aggressive disease. Current treatment options when the cancer is locally advanced are suboptimal and potentially mutilating. Insight into the immune dysregulation necessary for the emergence of penile cancer could suggest innovative ways to manipulate the immune system which have already demonstrated efficacy in other, more common malignancies. In this paper, we use multiplex immunofluorescence, a novel technology, to investigate the immune microenvironment of penile cancer for the first time. We describe a pattern of immune exhaustion as cancer becomes more advanced and identify tumor-associated macrophages as a potential key player in regulating this process. Penile squamous cell carcinoma (PSCC) is a rare and deadly malignancy. Therapeutic advances have been stifled by a poor understanding of disease biology. Specifically, the immune microenvironment is an underexplored component in PSCC and the activity of immune checkpoint inhibitors observed in a subset of patients suggests immune escape may play an important role in tumorigenesis. Herein, we explored for the first time the immune microenvironment of 57 men with PSCC and how it varies with the presence of human papillomavirus (HPV) infection and across tumor stages using multiplex immunofluorescence of key immune cell markers. We observed an increase in the density of immune effector cells in node-negative tumors and a progressive rise in inhibitory immune players such as type 2 macrophages and upregulation of the PD-L1 checkpoint in men with N1 and N2-3 disease. There were no differences in immune cell densities with HPV status. [ABSTRACT FROM AUTHOR]

Space-related stressors such as microgravity are associated with cellular and molecular alterations of the immune and inflammatory homeostasis that have been linked to the disorders that astronauts suffer from during their missions. Most of the research of the past 30 years has consistently established that innate adaptive immune cells represent a target of microgravity, which leads to their defective or dysfunctional activation, as well as to an altered ability to produce soluble mediators—e.g., cytokines/chemokines and bioactive lipids—that altogether control tissue homeostasis. Bioactive lipids include a vast array of endogenous molecules of immune origin that control the induction, intensity and outcome of the inflammatory events. However, none of the papers published so far focus on a newly characterized class of lipid mediators called specialized pro-resolving mediators (SPMs), which orchestrate the "resolution of inflammation"—i.e., the active control and confinement of the inflammatory torrent mostly driven by eicosanoids. SPMs are emerging as crucial players in those processes that avoid acute inflammation to degenerate into a chronic event. Given that SPMs, along with their metabolism and signaling, are being increasingly linked to many inflammatory disorders, their study seems of the outmost importance in the research of pathological processes involved in space-related diseases, also with the perspective of developing therapeutic countermeasures. Here, we show that microgravity, simulated in the rotary cell culture system (RCCS) developed by NASA, rearranges SPM receptors both at the gene and protein level, in human monocytes but not in lymphocytes. Moreover, RCCS treatment reduces the biosynthesis of a prominent SPM like resolvin (Rv) D1. These findings strongly suggest that not only microgravity can impair the functioning of immune cells at the level of bioactive lipids directly involved in proper inflammation, but it does so in a cell-specific manner, possibly perturbing immune homeostasis with monocytes being primary targets. [ABSTRACT FROM AUTHOR]

The elemental ratios of marine phytoplankton emerge from complex interactions between the biotic and abiotic components of the ocean, and reflect the plastic response of individuals to changes in their environment. The stoichiometry of phytoplankton is, thus, dynamic and dependent on the physiological state of the cell. We present a theoretical model for the dynamics of the carbon, nitrogen and phosphorus contents of a phytoplankton population. By representing the regulatory processes controlling nutrient uptake, and focusing on the relation between nutrient content and protein synthesis, our model qualitatively replicates existing experimental observations for nutrient content and ratios. The population described by our model takes up nutrients in proportions that match the input ratios for a broad range of growth conditions. In addition, there are two zones of single-nutrient limitation separated by a wide zone of co-limitation. Within the co-limitation zone, a single point can be identified where nutrients are supplied in an optimal ratio. The existence of a wide co-limitation zone affects the standard picture for species competing for nitrogen and phosphorus, which shows here a much richer pattern. However, additional comprehensive laboratory experiments are needed to test our predictions. Our model contributes to the understanding of the global cycles of oceanic nitrogen and phosphorus, as well as the elemental ratios of these nutrients in phytoplankton populations. [ABSTRACT FROM AUTHOR]

Time-lapse light microscopy combined with in vitro neuronal cultures has provided a significant contribution to the field of Developmental Neuroscience. The establishment of the neuronal polarity, i.e., formation of axons and dendrites, key structures responsible for inter-neuronal signaling, was described in 1988 by Dotti, Sullivan and Banker in a milestone paper that continues to be cited 30 years later. In the following decades, numerous fluorescently labeled tags and dyes were developed for live cell imaging, providing tremendous advancements in terms of resolution, acquisition speed and the ability to track specific cell structures. However, long-term recordings with fluorescence-based approaches remain challenging because of light-induced phototoxicity and/or interference of tags with cell physiology (e.g., perturbed cytoskeletal dynamics) resulting in compromised cell viability leading to cell death. Therefore, a label-free approach remains the most desirable method in long-term imaging of living neurons. In this paper we will focus on label-free high-resolution methods that can be successfully used over a prolonged period. We propose novel tools such as scanning ion conductance microscopy (SICM) or digital holography microscopy (DHM) that could provide new insights into live cell dynamics during neuronal development and regeneration after injury. [ABSTRACT FROM AUTHOR]

In recent years, sphingolipids have attracted significant attention due to their pivotal role in cellular functions and physiological diseases. A valuable tool for investigating the characteristics of sphingolipids can be represented via FT-IR spectroscopy, generally recognized as a very powerful technique that provides detailed biochemical information on the examined sample with the unique properties of sensitivity and accuracy. In the present paper, some fundamental aspects of sphingolipid components of human cells are summarized, and the most relevant articles devoted to the FT-IR spectroscopic studies of sphingolipids are revised. A short description of different FT-IR experimental approaches adopted for investigating sphingolipids is also given, with details about the most commonly used data analysis procedures. The present overview of FT-IR investigations, although not exhaustive, attests to the relevant role this vibrational technique has played in giving significant insight into many aspects of this fascinating class of lipids. [ABSTRACT FROM AUTHOR]

Cell biologists have long aimed at quantitatively modeling cell function. Recently, the outstanding progress of high-throughput measurement methods and data processing tools has made this a realistic goal. The aim of this paper is twofold: First, to suggest that, while much progress has been done in modeling cell states and transitions, current accounts of environmental cues driving these transitions remain insufficient. There is a need to provide an integrated view of the biochemical, topographical and mechanical information processed by cells to take decisions. It might be rewarding in the near future to try to connect cell environmental cues to physiologically relevant outcomes rather than modeling relationships between these cues and internal signaling networks. The second aim of this paper is to review exogenous signals that are sensed by living cells and significantly influence fate decisions. Indeed, in addition to the composition of the surrounding medium, cells are highly sensitive to the properties of neighboring surfaces, including the spatial organization of anchored molecules and substrate mechanical and topographical properties. These properties should thus be included in models of cell behavior. It is also suggested that attempts at cell modeling could strongly benefit from two research lines: (i) trying to decipher the way cells encode the information they retrieve from environment analysis, and (ii) developing more standardized means of assessing the quality of proposed models, as was done in other research domains such as protein structure prediction. [ABSTRACT FROM AUTHOR]

Background: Up to now, the physiology, pathology, and recovery of beta-cells have been intensively studied and made great progress, and these are of major significance for the treatment of related diseases. Nevertheless, a comprehensive and objective report on the status of beta-cell research is lacking. Therefore, this study aims to conduct a bibliometric analysis to quantify and identify the current status and trending issues in beta-cell research. Methods: The articles and reviews related to beta-cell were obtained from the Web of Science Core Collection on August 31, 2022. Two scientometric software (CiteSpace 6.1.R3 and VOSviewer 1.6.18) were used to perform bibliometric and knowledge-map analysis. Results: A total of 4098 papers were published in 810 academic journals in 2938 institutions from 83 countries/regions. The number of beta-cell-related publications was increasing steadily. The United States was the most productive country, while Universite libre de Bruxelles, University of Toronto and University of Geneva were the most active institutions. Diabetes published the most beta-cell studies and received the largest number of co-citations. Decio I Eizirik published the most papers and had the most co-citations. Twelve references on reviews and mechanisms were regarded as the knowledge base. Four major aspects of betacell research included the pathological mechanism of beta-cell failure, the recovery of beta cells, the risk factor related to beta cells, and the physiology of beta cells. Endoplasmic reticulum stress and oxidative stress have been core elements throughout the research in this field. In addition, beta-cell dedifferentiation, inflammation, autophagy, miRNA, and lncRNA are hot topics nowadays. Additionally, stem cell replacement therapies might be the alternative way to reverse beta-cell failure. Restoring beta-cell mass and function will remain a research goal in the future. Conclusion: This study provided a comprehensive overview of beta-cell research through bibliometric and visual methods. The information would provide helpful references for scholars focusing on beta cells. [ABSTRACT FROM AUTHOR]

This paper reports the simulation and optimization of the perovskitebased photovoltaic solar cell. The basic perovskite solar cell simulated in this work is a planar n–i–p structure. It consists of three different layers: a perovskite absorbing layer, which is sandwiched between the electrontransport layer (ETL) and the hole-transport layer (HTL). The present paper shows numerical simulations of a planar heterojunction solar cell having the following structure: FTO/ETL/perovskite/HTL/Au (FTO— fluorine-doped tin oxide). Formamidinium lead triiodide (FAPbI3) is used as perovskite absorber material; intrinsic tin oxide (i-SnO2) and tungsten disulphide (WS2) are used as electron-transport layer, and cuprous oxide (Cu2O) and Spiro-OMeTAD are used as hole-transport layer. The effects of the ETL and HTL types and the thickness of each layer are given by means of simulation using SCAPS-1D software. The obtained results show that a cell with WS2 (50 nm), FAPbI3 (750 nm) and Cu2O (10 nm) gives better efficiency of 26.07%. [ABSTRACT FROM AUTHOR]

The focuses on a study to examine the movements of single cells in early embryonic development using a recently developed technology. Researchers chose the chick embryos as an animal model. They used the multi-photon microscope, which can penetrate deep into tissues and obtain high-resolution three-dimensional images. To see the movements of individual cells, researchers used single lines to connect groups of three cells into triangles on each video frame. Then compared the movement of triangles in different regions of the embryo.

This paper proposes a deep learning-based method for mitosis detection in breast histopathology images. A main problem in mitosis detection is that most of the datasets only have weak labels, i.e., only the coordinates indicating the center of the mitosis region. This makes most of the existing powerful object detection methods hardly be used in mitosis detection. Aiming at solving this problem, this paper firstly applies a CNN-based algorithm to pixelwisely segment the mitosis regions, based on which bounding boxes of mitosis are generated as strong labels. Based on the generated bounding boxes, an object detection network is trained to accomplish mitosis detection. Experimental results show that the proposed method is effective in detecting mitosis, and the accuracies outperform state-of-the-art literatures. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic tumours present significant treatment challenges due to their resistance to chemotherapy and complex tumour microenvironment. Choosing the appropriate preclinical models and understanding how their characteristics affect drug delivery to the tumours is essential for designing clinically relevant experiments. This study investigates pancreatic tumours growing orthotopically or subcutaneously and presents the properties of their tumour microenvironments and their impacts on drug delivery. Pancreatic ductal adenocarcinoma (PDAC) remains a challenging malignancy, mainly due to its resistance to chemotherapy and its complex tumour microenvironment characterised by stromal desmoplasia. There is a need for new strategies to improve the delivery of drugs and therapeutic response. Relevant preclinical tumour models are needed to test potential treatments. This paper compared orthotopic and subcutaneous PDAC tumour models and their suitability for drug delivery studies. A novel aspect was the broad range of tumour properties that were studied, including tumour growth, histopathology, functional vasculature, perfusion, immune cell infiltration, biomechanical characteristics, and especially the extensive analysis of the structure and the orientation of the collagen fibres in the two tumour models. The study unveiled new insights into how these factors impact the uptake of a fluorescent model drug, the macromolecule called 800CW. While the orthotopic model offered a more clinically relevant microenvironment, the subcutaneous model offered advantages for drug delivery studies, primarily due to its reproducibility, and it was characterised by a more efficient drug uptake facilitated by its collagen organisation and well-perfused vasculature. The tumour uptake seemed to be influenced mainly by the structural organisation and the alignment of the collagen fibres and perfusion. Recognising the diverse characteristics of these models and their multifaceted impacts on drug delivery is crucial for designing clinically relevant experiments and improving our understanding of pancreatic cancer biology. [ABSTRACT FROM AUTHOR]

TAB182 participates in DNA damage repair and radio-/chemosensitivity regulation in various tumors, but its role in tumorigenesis and therapeutic resistance in breast cancer remains unclear. In the current paper, we observed that triple-negative Breast Cancer (TNBC), a highly aggressive type of breast cancer, exhibits a lower expression of TAB182. TAB182 knockdown stimulates the proliferation, migration, and invasion of TNBC cells. Our study first obtained RNA-seq data to explore the cellular functions mediated by TAB182 at the genome level in TNBC cells. A transcriptome analysis and in vitro experiments enabled us to identify that TAB182 downregulation drives the enhanced properties of cancer stem-like cells (CSCs) in TNBC cells. Furthermore, TAB182 deletion contributes to the resistance of cells to olaparib or cisplatin, which can be rescued by silencing GLI2, a gene downstream of cancer stemness-related signaling pathways. Our results reveal a novel function of TAB182 as a potential negative regulator of cancer stem-like properties and drug sensitivity in TNBC cells, suggesting that TAB182 may be a tumor suppressor gene and is associated with increased therapeutic benefits for TNBC patients. [ABSTRACT FROM AUTHOR]

The efficiency of antimony selenide (Sb2Se3) solar cells is still limited by significant interface and deep‐level defects, in addition to carrier recombination at the back contact surface. This paper investigates the use of lithium (Li) ions as dopant for Sb2Se3 films, using lithium hydroxide (LiOH) as a dopant medium. Surprisingly, the LiOH solution not only reacts at the back surface of the Sb2Se3 film but also penetrate inside the film along the (Sb4Se6)n molecular chain. First, the Li ions modify the grain boundary's carrier type and create an electric field between p‐type grain interiors and n‐type grain boundary. Second, a gradient band structure is formed along the vertical direction with the diffusion of Li ions. Third, carrier collection and transport are improved at the surface between Sb2Se3 and the Au layer due to the reaction between the film and alkaline solution. Additionally, the diffusion of Li ions increases the crystallinity, orientation, surface evenness, and optical electricity. Ultimately, the efficiency of Sb2Se3 solar cells is improved to 7.57% due to the enhanced carrier extraction, transport, and collection, as well as the reduction of carrier recombination and deep defect density. This efficiency is also a record for CdS/Sb2Se3 solar cells fabricated by rapid thermal evaporation. [ABSTRACT FROM AUTHOR]

The nuclear membrane serves a critical role in protecting the contents of the nucleus and facilitating material and signal exchange between the nucleus and cytoplasm. While extensive research has been dedicated to topics such as nuclear membrane assembly and disassembly during cell division, as well as interactions between nuclear transmembrane proteins and both nucleoskeletal and cytoskeletal components, there has been comparatively less emphasis on exploring the regulation of nuclear morphology through nuclear membrane integrity. In particular, the role of type II integral proteins, which also function as transcription factors, within the nuclear membrane remains an area of research that is yet to be fully explored. The integrity of the nuclear membrane is pivotal not only during cell division but also in the regulation of gene expression and the communication between the nucleus and cytoplasm. Importantly, it plays a significant role in the development of various diseases. This review paper seeks to illuminate the biomolecules responsible for maintaining the integrity of the nuclear membrane. It will delve into the mechanisms that influence nuclear membrane integrity and provide insights into the role of type II membrane protein transcription factors in this context. Understanding these aspects is of utmost importance, as it can offer valuable insights into the intricate processes governing nuclear membrane integrity. Such insights have broad-reaching implications for cellular function and our understanding of disease pathogenesis. [ABSTRACT FROM AUTHOR]

Simple Summary: Oncology is a rapidly advancing field in small-animal medicine, underscoring the importance of innovative therapeutic approaches. Tyrosine kinase inhibitors (TKIs) are drugs that block various important cellular functions and play an important role in treating cancer in people and dogs. However, their role in feline oncology is less established. This comprehensive review surveys the existing literature on tyrosine kinases (TKs) and the use of TKIs in cats, aiming to identify knowledge gaps, speculate on potential indications and lay the groundwork for future investigations. Diverse feline tissues have been examined for various TK expressions. However, although limited evidence exists on the use of TKIs in specific feline tumors, it trails behind progress in human and canine oncology. We believe additional research could identify new uses for these drugs and improve therapeutic options for cats with cancer in the future. Tyrosine kinase inhibitors (TKIs) have become invaluable in the treatment of human and canine malignancies, but their role in feline oncology is less defined. While toceranib phosphate and masitinib mesylate are licensed for use in dogs, no TKI is yet approved for cats. This review systematically maps the research conducted on the expression of tyrosine kinases in neoplastic and non-neoplastic domestic feline tissues, as well as the in vitro/in vivo use of TKIs in domestic cats. We identify and discuss knowledge gaps and speculate on the further research and potential indications for TKI use in cats. A comprehensive search of three electronic databases and relevant paper reference lists identified 139 studies meeting the inclusion criteria. The most commonly identified tumors were mast cell tumors (MCTs), mammary and squamous cell carcinomas and injection-site sarcomas. Based on the current literature, toceranib phosphate appears to be the most efficacious TKI in cats, especially against MCTs. Exploring the clinical use of TKIs in mammary carcinomas holds promise. Despite the progress, currently, the evidence falls short, underscoring the need for further research to discover new indications in feline oncology and to bridge the knowledge gaps between human and feline medicine. [ABSTRACT FROM AUTHOR]