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They demonstrated an increase in cell proliferation in Wharton's jelly-derived mesenchymal stem cells exposed to pressure stimuli during the primary step of culture without causing alteration changes in the stemness biology [[21]]. The papers in the Special Issue "Mechanobiology in Cells and Tissues" explored the multidisciplinary aspects of mechanobiology and highlighted the role of cell mechanobiology in physiology and pathology. Mechanobiology pathways are also essential for cardiac cells' function over their lifespan [[11]], and therefore, innovative therapeutic approaches attempt to regenerate the damaged tissue by re-establishing the mechanical microenvironment (e.g., stiffness range, topography, and viscoelasticity). Our group also provided an overview of the molecular basis of mechanosensing and mechanotransduction pathways, and of their role in the cross-talk between stem cells and microenvironments, and how these dynamic interplays are critical in the control of stem cell identity and function, including their therapeutic application in regenerative medicine [[2]]. [Extracted from the article]

Simple Summary: Liver cancer continues to exhibit increasing incidence and mortality worldwide. Subsequently, there has been a concomitant effort to development novel therapeutics that effectively target and treat these malignancies. This paper aims to provide a thorough review of the available immunotherapy treatments that target liver cancer, with a specific focus on the role and potential therapeutic strategies available to the interventional radiologist. The underlying biochemical and molecular mechanisms underlying these diseases are discussed to highlight the specific targets for immunotherapy, the clinical efficacy and safety of available pharmaceutical treatments are analyzed, and future advancements in the field, such as combination therapies and personalized medicine, are explored as they pertain to the immunotherapy of liver cancer. Liver cancer, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, is increasing in incidence and mortality across the globe. An improved understanding of the complex tumor microenvironment has opened many therapeutic doors and led to the development of novel pharmaceuticals targeting cellular signaling pathways or immune checkpoints. These interventions have significantly improved tumor control rates and patient outcomes, both in clinical trials and in real-world practice. Interventional radiologists play an important role in the multidisciplinary team given their expertise in minimally invasive locoregional therapy, as the bulk of these tumors are usually in the liver. The aim of this review is to highlight the immunological therapeutic targets for primary liver cancers, the available immune-based approaches, and the contributions that interventional radiology can provide in the care of these patients. [ABSTRACT FROM AUTHOR]

Several studies and research papers have been published to elucidate and understand the mechanism of the coronavirus disease 2019 (COVID-19) pandemic and its long-term effects on the human body. COVID-19 affects a number of organs, including the female reproductive system. However, less attention has been given to the effects of COVID-19 on the female reproductive system due to their low morbidity. The results of studies investigating the relationship between COVID-19 infection and ovarian function in women of reproductive age have shown the harmless involvement of COVID-19 infection. Several studies have reported the involvement of COVID-19 infection in oocyte quality, ovarian function, and dysfunctions in the uterine endometrium and the menstrual cycle. The findings of these studies indicate that COVID-19 infection negatively affects the follicular microenvironment and dysregulate ovarian function. Although the COVID-19 pandemic and female reproductive health have been studied in humans and animals, very few studies have examined how COVID-19 affects the female reproductive system. The objective of this review is to summarize the current literature and categorize the effects of COVID-19 on the female reproductive system, including the ovaries, uterus, and hormonal profiles. The effects on oocyte maturation, oxidative stress, which causes chromosomal instability and apoptosis in ovaries, in vitro fertilization cycle, high-quality embryos, premature ovarian insufficiency, ovarian vein thrombosis, hypercoagulable state, women's menstrual cycle, the hypothalamus-pituitary-ovary axis, and sex hormones, including estrogen, progesterone, and the anti- Müllerian hormone, are discussed in particular. [ABSTRACT FROM AUTHOR]

The CD34 protein was identified almost four decades ago as a biomarker for hematopoietic stem cell progenitors. CD34 expression of these stem cells has been exploited for therapeutic purposes in various hematological disorders. In the last few decades, studies have revealed the presence of CD34 expression on other types of cells with non-hematopoietic origins, such as interstitial cells, endothelial cells, fibrocytes, and muscle satellite cells. Furthermore, CD34 expression may also be found on a variety of cancer stem cells. Nowadays, the molecular functions of this protein have been involved in a variety of cellular functions, such as enhancing proliferation and blocking cell differentiation, enhanced lymphocyte adhesion, and cell morphogenesis. Although a complete understanding of this transmembrane protein, including its developmental origins, its stem cell connections, and other functions, is yet to be achieved. In this paper, we aimed to carry out a systematic analysis of the structure, functions, and relationship with cancer stem cells of CD34 based on the literature overview. [ABSTRACT FROM AUTHOR]

Simple Summary: The tumor microenvironment (TME) has a vital role in cancer development, progression, and metastasis. It can shape immune infiltration and activation within tumors, including the role of macrophages, tumor effector cells, and the uptake of therapeutic drugs or nanoparticles. In this manuscript, we report on the feasibility and preliminary efficacy of administering E. coli phagelysate (EcPHL) as a primer to modify the TME, including the enhanced uptake of magnetic nanoparticles (mNP) by tumor-associated macrophages (TAM) and tumor cells. The tumor microenvironment (TME), where cancer cells reside, plays a crucial role in cancer progression and metastasis. It maintains an immunosuppressive state in many tumors and regulates the differentiation of precursor monocytes into M1 (anti-tumor)- and M2 (pro-tumor)-polarized macrophages, and greatly reduces anticancer drug and nanoparticle delivery. As a result, the effectiveness of recently developed chemo- and/or nanotechnology-mediated immune and magnetic nanoparticle hyperthermia (mNPH) therapies is inhibited significantly. One of the ways to overcome this limitation is to use E. coli phagelysate as a primer to modify the tumor microenvironment by switching tumor-associated M2 macrophages to anti-tumor M1 macrophages, and initiate the infiltration of tumor-associated macrophages (TAMs). Recently, bacteriophages and phage-induced lysed bacteria (bacterial phagelysates—BPLs) have been shown to be capable of modifying the tumor-associated environment. Phage/BPL-coated proteins tend to elicit strong anti-tumor responses from the innate immune system, prompting phagocytosis and cytokine release. It has also been reported that the microenvironments of bacteriophage- and BPL-treated tumors facilitate the conversion of M2-polarized TAMS to a more M1-polarized (tumoricidal) environment post-phage treatment. This paper demonstrates the feasibility and enhanced efficacy of combining E. coli phagelysate (EcPHL) and mNPH, a promising technology for treating cancers, in a rodent model. Specifically, we illustrate the EcPHL vaccination effect on the TME and mNP distribution in Ehrlich adenocarcinoma tumors by providing the tumor growth dynamics and histology (H&E and Prussian blue) distribution of mNP in tumor and normal tissue. [ABSTRACT FROM AUTHOR]

This paper investigated the effect and mechanism of theaflavins (TFs) on fluoride (F−) uptake and transport in the Caco-2 cell model through structural chemistry and transcriptome analysis. The results showed that the four major TFs (TF, TF3G, TF3′G and TFDG) at a 150 μg/mL concentration could all significantly decrease F− transport in Caco-2 cells after 2 h of treatment and, at 2 μg/mL F− concentration, the F− transport was more inclined to efflux. During transport, the F− retention in Caco-2 cells was significantly increased by TF3G while it was clearly decreased by TF. The interaction between TFs and F− was analyzed by Raman spectroscopy and isothermal titration calorimetry, and F− was shown to affect the π bond vibration on the benzene ring of TFs, thus influencing their stability. Additionally, F− showed weak binding to TF3G, TF3′G and TFDG, which may inhibit F− transport and absorption in the Caco-2 cell line. Transcriptome and RT-PCR analysis identified three key differentially expressed genes related to cell permeability, and TFs can be assumed to mediate F− transport by regulating the expression of permeability-related genes to change cell monolayer permeability and enhance cell barrier function; however, this needs to be further elucidated in future studies. [ABSTRACT FROM AUTHOR]

Autophagy is a highly conserved process that maintains cell stability in eukaryotes, participates in the turnover of intracellular substances to maintain cell function, helps to resist pathogen invasion, and improves cell tolerance to environmental changes. Autophagy has been observed in many diseases, and the symptoms of these diseases are significantly improved by regulating autophagy. Autophagy is also involved in the development of lung diseases. Studies have shown that autophagy may play a beneficial or harmful role in acute lung injury (ALI), and ALI has been treated with traditional Chinese medicine designed to promote or inhibit autophagy. In this paper, the molecular mechanism and common pathways regulating autophagy and the relationship between autophagy and ALI are introduced, and the active ingredients of traditional Chinese medicine that improve ALI symptoms by regulating autophagy are summarized. [ABSTRACT FROM AUTHOR]

In 2020, a total of 106 original research articles, 84 reviews, and 1 other paper were published within the "Cell Nuclei: Function, Transport and Receptors" section. The overexpression of progerin resulted in an induction of endothelial cell dysfunction characterized by increased inflammation, oxidative stress along with persistent DNA damage, an elevated expression of cell cycle arrest proteins, and cellular senescence. 33003364 13 Conti I., Varano G., Simioni C., Laface I., Milani D., Rimondi E., Neri L.M. miRNAs as influencers of cell-cell communication in tumor microenvironment. [Extracted from the article]

Simple Summary: The glaziovianin A derivative gatastatin, presented as a γ-tubulin-specific inhibitor, could represent a viable chemotherapeutic strategy to solve the specificity issues associated with targeting α and β tubulin. Since gatastatin's specificity for γ tubulin has not been confirmed by an in silico analysis or verified experimentally by other groups, we undertook finding a molecular-level elucidation of the binding mode of gatastatin and comparing its predicted binding affinity values for both α-β and γ tubulin. We believe that our paper opens the possibility for the rational design of a long-sought candidate drug with desired specificity and selectivity for γ tubulin. Given its critical role in cell mitosis, the tubulin γ chain represents a viable chemotherapeutic target to solve the specificity issues associated with targeting α and β tubulin. Since γ tubulin is overexpressed in glioblastoma multiforme (GBM) and some breast lesions, the glaziovianin A derivative gatastatin, presented as a γ-tubulin-specific inhibitor, could yield a successful therapeutic strategy. The present work aims to identify the binding sites and modes of gatastatin and its derivatives through molecular-docking simulations. Computational binding free energy predictions were compared to experimental microscale thermophoresis assay results. The computational simulations did not reveal a strong preference toward γ tubulin, suggesting that further derivatization may be needed to increase its specificity. [ABSTRACT FROM AUTHOR]

Major advances have been achieved in imaging technologies but most methodological approaches currently used to study the enteric neuronal functions rely on exogenous contrast dyes that can interfere with cellular functions or survival. In the present paper, we investigated whether full-field optical coherence tomography (FFOCT), could be used to visualize and analyze the cells of the enteric nervous system. Experimental work on whole-mount preparations of unfixed mouse colons showed that FFOCT enables the visualization of the myenteric plexus network whereas dynamic FFOCT enables to visualize and identify in situ individual cells in the myenteric ganglia. Analyzes also showed that dynamic FFOCT signal could be modified by external stimuli such veratridine or changes in osmolarity. These data suggest that dynamic FFOCT could be of great interest to detect changes in the functions of enteric neurons and glia in normal and disease conditions. Full-field optical coherence tomography (FFOCT) can be used for the visualization of the myenteric plexus network and individual myenteric ganglia cells in situ, showing that FFOCT is a suitable method to image enteric nervous system activity. [ABSTRACT FROM AUTHOR]

The initiation and progression of tumors are complex. The cancer evolution-development hypothesis holds that the dysregulation of immune balance is caused by the synergistic effect of immune genetic factors and environmental factors that stimulate and maintain non-resolving inflammation. Throughout the cancer development process, this inflammation creates a microenvironment for the evolution and development of cancer. Research on the inflammatory tumor microenvironment (TME) explains the initiation and progression of cancer and guides anti-cancer immunotherapy. Single-cell RNA sequencing (scRNA-seq) can detect the transcription levels of cells at the single-cell resolution level, reveal the heterogeneity and evolutionary trajectory of infiltrated immune cells and cancer cells, and provide insight into the composition and function of each cell group in the inflammatory TME. This paper summarizes the application of scRNA-seq in inflammatory TME. [ABSTRACT FROM AUTHOR]

Simple Summary: B cells are increasingly appreciated as important contributors to the tumor microenvironment in a myriad of cancer histologies, including sarcoma. In sarcoma, recent investigations have revealed associations between B cell expression signatures, the presence of tertiary lymphoid structures, and responses to immunotherapy. In this paper, we aim to provide a comprehensive review of the multiple putative roles of B cells in sarcoma, including a historical overview, an assessment of B cells within the sarcoma microenvironment, the role of tertiary lymphoid structures, the relationship between immunotherapy efficacy and B cell signatures, sarcoma antigens and anti-tumor antibodies, pro-tumor B cell relationships, and future research directions. Despite being one of the first types of cancers studied that hinted at a major role of the immune system in pro- and anti-tumor biology, little is known about the immune microenvironment in sarcoma. Few types of sarcoma have shown major responses to immunotherapy, and its rarity and heterogeneity makes it challenging to study. With limited systemic treatment options, further understanding of the underlying mechanisms in sarcoma immunity may prove crucial in advancing sarcoma care. While great strides have been made in the field of immunotherapy over the last few decades, most of these efforts have focused on harnessing the T cell response, with little attention on the role B cells may play in the tumor microenvironment. A growing body of evidence suggests that B cells have both pro- and anti-tumoral effects in a large variety of cancers, and in the age of bioinformatics and multi-omic analysis, the complexity of the humoral response is just being appreciated. This review explores what is currently known about the role of B cells in sarcoma, including understanding the various B cell populations associated with sarcoma, the organization of intra-tumoral B cells in tertiary lymphoid structures, recent trials in immunotherapy in sarcoma, intra-tumoral immunoglobulin, the pro-tumor effects of B cells, and exciting future areas for research. [ABSTRACT FROM AUTHOR]

Amyloid aggregates play a major role in diseases as well as in normal physiological function. Receptor-interacting protein kinases 1 and 3 (RIP1/RIP3) aggregates complexes in cellular necroptosis is one example of protein aggregation in normal cellular function. Although recently there have been several studies on full kinase proteins aggregation, the aggregation potential of small peptide sequences of RIP1/RIP3, the physicochemical properties, and the potential in biomedical applications have not been explored. Hence, in this paper, we study the aggregation propensity of peptides consisting of four and twelve amino acid sequences in the RHIM region of RIP1/RIP3 proteins that are known to drive the beta-sheet formation and the subsequent aggregation. The aggregation kinetics, physicochemical characterization, mechanosensitive properties, cellular effects, and potential as a cancer drug depot have been investigated. The results show that the number and concentration of amino acids play a role in amyloid-like aggregates' properties. Further, the aggregates when formulated with cisplatin-induced significant lung cancer cell toxicity compared to an equal amount of cisplatin with and without ultrasound. The study would serve as a platform for further investigation on RIP1/RIP3 peptide and protein aggregates, their role in multiple cellular functions and diseases, and their potential as drug depots. [ABSTRACT FROM AUTHOR]

ROS in cancer cells play a key role in pathways regulating cell death, stemness maintenance, and metabolic reprogramming, all of which have been implicated in resistance to chemo/ immunotherapy. Adjusting ROS levels to reverse the resistance of cancer cells without impairing normal cell functions is a new therapeutic avenue. In this paper, we describe new inhibitors of NADPH oxidase (NOX), a key enzyme in many cells of the tumor microenvironment. The first inhibitor, called Nanoshutter-1, NS1, decreased the level of tumor-promoting "M2" macrophages differentiated from human blood monocytes. NS1 disrupted the active NADPH oxidase-2 (NOX2) complex at the membrane and in the mitochondria of the macrophages, as shown by confocal microscopy. As one of the characteristics of tumor invasion is hypoxia, we tested whether NS1 would affect vascular reactivity by reducing ROS or NO levels in wire and pressure myograph experiments on isolated blood vessels. The results show that NS1 vasodilated blood vessels and would likely reduce hypoxia. Finally, as both NOX2 and NOX4 are key proteins in tumors and their microenvironment, we investigated whether NS1 would probe these proteins differently. Models of NOX2 and NOX4 were generated by homology modeling, showing structural differences at their C-terminal NADPH site, in particular in their last Phe. Thus, the NADPH site presents an unexploited chemical space for addressing ligand specificity, which we exploited to design a novel NOX2-specific inhibitor targeting variable NOX2 residues. With the proper smart vehicle to target specific cells of the microenvironment as TAMs, NOX2-specific inhibitors could open the way to new precision therapies. [ABSTRACT FROM AUTHOR]

Simple Summary: Postparturient hemoglobinuria is a rare but deadly disease of dairy cows. Cows are affected mainly in the period closely following calving. The main clinical sign—the passing of strongly discolored urine—is caused by the breakdown of red blood cells within the bloodstream. The condition is generally believed to be associated with a dietary phosphorus deficiency, but the precise etiology is unknown. We, therefore, designed two studies to explore the effect of phosphorus deprivation on red blood cell form and function. In the first study, we fed a ration low in phosphorus for four weeks before to four weeks after calving. In the second study, we restricted phosphorus only before calving. Feeding a diet low in phosphorus throughout the periparturient period (Study I), resulted in severe anemia and hemoglobinuria in a subset of cows after calving. In addition, a subclinical form of the disease was discovered. The results provide insight into, and increase awareness of, the occurrence of postparturient hemoglobinuria and the role of phosphorus. Postparturient hemoglobinuria is a sporadic disease characterized by intravascular hemolysis and hemoglobinuria in early lactating dairy cows. The condition has empirically been associated with phosphorus (P) deficiency or hypophosphatemia; however, the exact etiology remains obscure. This paper summarizes two controlled studies investigating the effect of P deprivation during the transition period. In Study I, 36 late pregnant dairy cows were randomly assigned to either a diet with low, or adequate, P content from four weeks before calving to four weeks after calving. In Study II, 30 late pregnant dairy cows were again assigned to either a diet with low, or adequate, P for the last four weeks before calving only. Pronounced hypophosphatemia developed during periods of restricted P supply. In early lactation, a subtle decline of the red blood cell count occurred independently of the dietary P supply. In Study I, anemia developed in 11 cows on deficient P supply, which was associated with hemoglobinuria in five cases. Neither erythrocyte total P content nor osmotic resistance of erythrocytes were altered by dietary P deprivation. Restricted dietary P supply, particularly in early lactation, may lead to postparturient hemoglobinuria, but more frequently causes clinically inapparent hemolysis and anemia in cows. [ABSTRACT FROM AUTHOR]

Introduction: The potential mechanisms governing drug induced osteonecrosis of the jaw (ONJ) is not well understood, and is one of the objectives of this study. Thus, we tested the release of IFN-g within different immune compartments including bone marrow and gingivae upon treatment with zoledronic acid (ZOL) and denosumab which are known to induce ONJ in susceptible individuals. Methods: We used humanized-BLT mouse model for the in-vivo studies reported in this paper. To determine the effects of zoledronic acid and denosumab on IFN-g secretion and NK cell-mediated cytotoxicity; peripheral blood, bone marrow, spleen and gingiva were obtained after the injection of ZOL and denosumab in mice. Results: Percentages of B cells are much higher in wild-type mice whereas the proportions of immune subsets in humans and reconstituted hu-BLT peripheralblood are similar. Therefore, hu-BLT mice are preferable model to study human disease, in particular, immune-pathologies induced by ZOL and denosumab. Both agents resulted in a severe suppression of IFN-g in the gingiva, whereas they heightened the release of IFN-g and NK cell-mediated cytotoxicity by the BMderived immune cells. ZOL increased the IFN-g secretion by the spleen and peripheral blood immune cells, whereas denosumab decreased the release IFNg by these cells significantly. Discussion: ZOL and denosumab may likely suppress IFN-g secretion in gingiva through different mechanisms. In addition, to the suppression of IFN-g secretion, denosumab mediated effect could in part be due to the decrease in the bone resorptive function of osteoclasts due to the induction of antibody dependent cellular cytotoxicity and lysis of osteoclasts, whereas ZOL is able to mediate cell death of osteoclasts directly. Suppression of IFN-gamma in gingiva is largely responsible for the inhibition of immune cell function, leading to dysregulated osteoblastic and osteoclastic activities. Restoration of IFN-gamma in the local microenvironment may result in establishment of homeostatic balance in the gingiva and prevention of osteonecrosis of jaw. [ABSTRACT FROM AUTHOR]

Simple Summary: Tumors are not masses of cancer cells alone but made up of cancer cells, other cells including fibroblasts, macrophages, endothelial cells, as well as secreted factors, blood vessels and the extracellular matrix (ECM). This comprehensive review presents new findings on the role of each component of the tumor cell surroundings and the effect on the success of cancer drugs. We show in this paper that the tumor cell's surroundings are not simply 'bystanders' but are actively involved in tumor growth and can cause resistance to treatment. Initially, cells and ECM around tumor cells do not promote their growth but over time, tumor cells 'convert' their surroundings to promote their growth. An increase in tumor size means tumor cells must overcome a lack of oxygen and nutrients, be able to remove waste and form secondary tumors. A better knowledge of tumor cells and their surrounding means better drugs for tumor cells and their surroundings. Tumorigenesis is a complex and dynamic process involving cell-cell and cell-extracellular matrix (ECM) interactions that allow tumor cell growth, drug resistance and metastasis. This review provides an updated summary of the role played by the tumor microenvironment (TME) components and hypoxia in tumorigenesis, and highlight various ways through which tumor cells reprogram normal cells into phenotypes that are pro-tumorigenic, including cancer associated- fibroblasts, -macrophages and -endothelial cells. Tumor cells secrete numerous factors leading to the transformation of a previously anti-tumorigenic environment into a pro-tumorigenic environment. Once formed, solid tumors continue to interact with various stromal cells, including local and infiltrating fibroblasts, macrophages, mesenchymal stem cells, endothelial cells, pericytes, and secreted factors and the ECM within the tumor microenvironment (TME). The TME is key to tumorigenesis, drug response and treatment outcome. Importantly, stromal cells and secreted factors can initially be anti-tumorigenic, but over time promote tumorigenesis and induce therapy resistance. To counter hypoxia, increased angiogenesis leads to the formation of new vascular networks in order to actively promote and sustain tumor growth via the supply of oxygen and nutrients, whilst removing metabolic waste. Angiogenic vascular network formation aid in tumor cell metastatic dissemination. Successful tumor treatment and novel drug development require the identification and therapeutic targeting of pro-tumorigenic components of the TME including cancer-associated- fibroblasts (CAFs) and -macrophages (CAMs), hypoxia, blocking ECM-receptor interactions, in addition to the targeting of tumor cells. The reprogramming of stromal cells and the immune response to be anti-tumorigenic is key to therapeutic success. Lastly, this review highlights potential TME- and hypoxia-centered therapies under investigation. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a neurodegenerative disorder that results from the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Since there are only symptomatic treatments available, new cellular and molecular targets involved in the onset and progression of this disease are needed to develop effective treatments. CCAAT/Enhancer Binding Protein β (C/EBPβ) transcription factor levels are altered in patients with a variety of neurodegenerative diseases, suggesting that it may be a good therapeutic target for the treatment of PD. A list of genes involved in PD that can be regulated by C/EBPβ was generated by the combination of genetic and in silico data, the mitochondrial transcription factor A (TFAM) being among them. In this paper, we observed that C/EBPβ overexpression increased TFAM promoter activity. However, downregulation of C/EBPβ in different PD/neuroinflammation cellular models produced an increase in TFAM levels, together with other mitochondrial markers. This led us to propose an accumulation of non-functional mitochondria possibly due to the alteration of their autophagic degradation in the absence of C/EBPβ. Then, we concluded that C/EBPβ is not only involved in harmful processes occurring in PD, such as inflammation, but is also implicated in mitochondrial function and autophagy in PD-like conditions. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is distinguished by the absence of human epidermal growth factor 2 receptors, estrogen, and progesterone. Due to its destructive character and inability to be treated with current endocrine medications, it has one of the worst prognoses of any breast cancer subtype. The only therapies available are chemo-and/or radiation and surgery, which necessitates the development of new biomarkers or therapeutic targets. Due to of their inherent inclination to operate as antisense regulators and interactors of whole gene set implicated in cancer, microRNAs (miRNAs) are a potential target for TNBC-focused therapy. In this paper, we summarize the role of epigenetics variation with a focus on DNA methylation in TNBC patients. Other biomarkers alterations and interactions with miRNAs may lead to the identification of novel therapy options for TNBC in the future as well. [ABSTRACT FROM AUTHOR]

In this work, we present a method to study thermal runaway effects in thin-film solar cells. Partial shading of solar cells often leads to permanent damage to shaded cells and degrades the performance of solar modules over time. Under partial shading, the shaded cells may experience a reverse bias junction breakdown. In large-area devices such as solar cells, this junction breakdown tends to take place very locally, thus leading to very local heating and so-called "hot-spots". Previously, it was shown that a positive feedback effect exists in Cu(In,Ga)Se2 (CIGS) thin-film solar cells, where a highly localized power dissipation is amplified, which may lead to an unstable thermal runaway process. Furthermore, we introduced a novel characterization technique, laser induced Hot-Spot Lock-In Thermography (HS-LIT), which visualizes the positive feedback effect. In this paper, we present a modified HS-LIT technique that allows us to quantify directly a loop-gain for hot-spot formation. By quantifying the loop-gain we obtain a direct measure of how unstable a local hot-spot is, which allows the non-destructive study of hot-spot formation under various conditions and in various cells and cell types. We discuss the modified HS-LIT setup for the direct measurement of the loop-gain. Furthermore, we demonstrate the new method by measuring the loop-gain of the thermal runaway effect in a CIGS solar cell as a function of reverse bias voltage. [ABSTRACT FROM AUTHOR]

As one of the most important parameters of biochemical analysis and detection, the pH value plays a very important role in cell function, food preservation and production, soil and water sources, and other applications. This makes it increasingly important to explore pH detection methods in depth. In this paper, a pH-responsive SERS probe based on the cyano Raman Tag was designed to realize pH sensing detection through the influence of the pH value of analytes on the displacement of the cyano Raman peak in the SERS probe. This cyano Raman tag exhibited not only excellent sensitivity in the liner range of pH 3.0–9.0 with a limit of detection (LOD) of pH 0.33, but also the anti-interference performance and stability (the relative standard deviation (RSD) was calculated to be 6.68%, n = 5). These results indicated that this pH SERS probe with the Raman cyano tag can provide new research ideas for future biological detection, bioimaging, and environmental detection. [ABSTRACT FROM AUTHOR]

Endo-ß-1,4-glucanase AkEG21 belonging to glycosyl hydrolase family 45 (GHF45) is the most abundant cellulase in the digestive fluid of sea hare (Aplysia kurodai). The specific activity of this 21-kDa enzyme is considerably lower than those of other endo ß-1,4-glucanases in the digestive fluid of A. kurodai, therefore its role in whole cellulose hydrolysis by sea hare is still uncertain. Although AkEG21 has a catalytic domain without a cellulose binding domain, it demonstrated stable binding to cellulose fibers, similar to that of fungal cellobiohydrolase (CBH) 1 and CBH 2, which is strongly inhibited by cellohexaose, suggesting the involvement of the catalytic site in cellulose binding. Cellulose-bound AkEG21 hydrolyzed cellulose to cellobiose, cellotriose and cellotetraose, but could not digest an external substrate, azo-carboxymethyl cellulose. Cellulose hydrolysis was considerably stimulated by the synergistic action of cellulose-bound AkEG21 and AkEG45, another ß-1,4-endoglucanase present in the digestive fluid of sea hare; however no synergy in carboxymethylcellulose hydrolysis was observed. When AkEG21 was removed from the digestive fluid by immunoprecipitation, the cellulose hydrolyzing activity of the fluid was significantly reduced, indicating a critical role of AkEG21 in cellulose hydrolysis by A. kurodai. These findings suggest that AkEG21 is a processive endoglucanase functionally equivalent to the CBH, which provides a CBH-independent mechanism for the mollusk to digest seaweed cellulose to glucose. [ABSTRACT FROM AUTHOR]

The quality of life of diabetic patients is seriously affected by wound healing difficulty, which can lead to increased infection, skin deep tissue injury and continuous pain. By analyzing the research trends and hot spots in this field, the visualization analysis map is constructed. Methods: The contents of the selected articles were sorted out and analyzed by bibliometrics. We use CiteSpace, Vosviewer and HistCite to visualize literature information, including national publication statistics, institutions, authors, journal partnerships, and citations of published articles. Results: Among the 2942 articles, the United States and China ranked first in both article circulation and TGCS, and many countries also cooperated. The collaboration between schools and research institutions is a core part of dissertation research institution collaboration, with most authors coming from the same institution. Most of the literature studies on the mechanisms and methods of promoting diabetic wound healing. Improving cell function or making innovative attempts in local treatment are the fruits of researchers' efforts to promote diabetic wound healing in recent years. Conclusion: Through the metrology method, the time distribution, author institution, cooperation network, research status, research hotspot and development trend of the literature on the influence of diabetes on wound healing were intuitively displayed, which provided a reference for further research and development direction. [ABSTRACT FROM AUTHOR]

Simple Summary: Osteosarcoma is the most common type of bone cancer seen in children to young adults with poor prognosis. To find effective treatments, it is crucial to understand the mechanism of the initiation and progression of the osteosarcoma tumors. In this paper, we introduce a PDE model for the progression of osteosarcoma tumors by considering the location of different cell types, including immune and cancer cells, in the tumors. We perform several simulations using the developed model to investigate the importance and role of the different immune cells' location in the growth of the tumors. The results show that the co-localization of macrophages and cancer cells promotes tumors' growth. Osteosarcoma is the most common malignant bone tumor in children and adolescents with a poor prognosis. To describe the progression of osteosarcoma, we expanded a system of data-driven ODE from a previous study into a system of Reaction-Diffusion-Advection (RDA) equations and coupled it with Biot equations of poroelasticity to form a bio-mechanical model. The RDA system includes the spatio-temporal information of the key components of the tumor microenvironment. The Biot equations are comprised of an equation for the solid phase, which governs the movement of the solid tumor, and an equation for the fluid phase, which relates to the motion of cells. The model predicts the total number of cells and cytokines of the tumor microenvironment and simulates the tumor's size growth. We simulated different scenarios using this model to investigate the impact of several biomedical settings on tumors' growth. The results indicate the importance of macrophages in tumors' growth. Particularly, we have observed a high co-localization of macrophages and cancer cells, and the concentration of tumor cells increases as the number of macrophages increases. [ABSTRACT FROM AUTHOR]

Biogenic amines (BAs) occur in a wide variety of foodstuffs, mainly from the decomposition of proteins by the action of microorganisms. They are involved in several cellular functions but may become toxic when ingested in high amounts through the diet. In the case of oenological products, BAs are already present in low concentrations in must, and their levels rise dramatically during the fermentation processes. This paper proposes a rapid method for the determination of BAs in wines and related samples based on precolumn derivatization with dansyl chloride and further detection by flow injection analysis with tandem mass spectrometry. Some remarkable analytes such as putrescine, ethanolamine, histamine, and tyramine have been quantified in the samples. Concentrations obtained have shown interesting patterns, pointing out the role of BAs as quality descriptors. Furthermore, it has been found that the BA content also depends on the vinification practices, with malolactic fermentation being a significant step in the formation of BAs. From the point of view of health, concentrations found in the samples are, in general, below 10 mg L−1, so the consumption of these products does not represent any special concern. In conclusion, the proposed method results in a suitable approach for a fast screening of this family of bioactive compounds in wines to evaluate quality and health issues. [ABSTRACT FROM AUTHOR]

Regulatory T cells (Tregs) are the master regulators of immunity and they have been implicated in different disease states such as infection, autoimmunity and cancer. Since their discovery, many studies have focused on understanding Treg development, differentiation, and function. While there are many players in the generation and function of truly suppressive Tregs, the role of checkpoint pathways in these processes have been studied extensively. In this paper, we systematically review the role of different checkpoint pathways in Treg homeostasis and function. We describe how co-stimulatory and coinhibitory pathways modulate Treg homeostasis and function and highlight data from mouse and human studies. Multiple checkpoint pathways are being targeted in cancer and autoimmunity; therefore, we share insights from the clinic and discuss the effect of experimental and approved therapeutics on Treg biology. [ABSTRACT FROM AUTHOR]

Cytoskeleton proteins have been long recognized as structural proteins that provide the necessary mechanical architecture for cell development and tissue homeostasis. With the completion of the cancer genome project, scientists were surprised to learn that huge numbers of mutated genes are annotated as cytoskeletal or associated proteins. Although most of these mutations are considered as passenger mutations during cancer development and evolution, some genes show high mutation rates that can even determine clinical outcomes. In addition, (phospho)proteomics study confirms that many cytoskeleton-associated proteins, e.g., β-catenin, PIK3CA, and MB21D2, are important signaling mediators, further suggesting their biofunctional roles in cancer development. With emerging evidence to indicate the involvement of mechanotransduction in stemness formation and cell differentiation, mutations in these key cytoskeleton components may change the physical/mechanical properties of the cells and determine the cell fate during cancer development. In particular, tumor microenvironment remodeling triggered by such alterations has been known to play important roles in autophagy, metabolism, cancer dormancy, and immune evasion. In this review paper, we will highlight the current understanding of how aberrant cytoskeleton networks affect cancer behaviors and cellular functions through mechanotransduction. [ABSTRACT FROM AUTHOR]

Nanoarchitectonics has emerged as a post-nanotechnology concept. As one of the applications of nanoarchitectonics, this review paper discusses the control of stem cell fate and function as an important issue. For hybrid nanoarchitectonics involving living cells, it is crucial to understand how biomaterials and their nanoarchitected structures regulate behaviours and fates of stem cells. In this review, biomaterials for the regulation of stem cell fate are firstly discussed. Besides multipotent differentiation, immunomodulation is an important biological function of mesenchymal stem cells (MSCs). MSCs can modulate immune cells to treat multiple immune- and inflammation-mediated diseases. The following sections summarize the recent advances of the regulation of the immunomodulatory functions of MSCs by biophysical signals. In the third part, we discussed how biomaterials direct the self-organization of pluripotent stem cells for organoid. Bioactive materials are constructed which mimic the biophysical cues of in vivo microenvironment such as elasticity, viscoelasticity, biodegradation, fluidity, topography, cell geometry, and etc. Stem cells interpret these biophysical cues by different cytoskeletal forces. The different cytoskeletal forces lead to substantial transcription and protein expression, which affect stem cell fate and function. Regulations of stem cells could not be utilized only for tissue repair and regenerative medicine but also potentially for production of advanced materials systems. Materials nanoarchitectonics with integration of stem cells and related biological substances would have high impacts in science and technology of advanced materials. [ABSTRACT FROM AUTHOR]

Due to their unprecedented ability to flexibly manipulate the parameters of light, metasurfaces offer a new approach to integrating multiple functions in a single optical element. In this paper, based on a single-celled metasurface composed of chiral umbrella-shaped metal–insulator–metal (MIM) unit cells, a strategy for simultaneous multiple polarization generation and wavefront shaping is proposed. The unit cells can function as broadband and high-performance polarization-preserving mirrors. In addition, by introducing a chiral-assisted Aharonov–Anandan (AA) geometric phase, the phase profile and phase retardation of two spin-flipped orthogonal circular polarized components can be realized simultaneously and independently with a single-celled metasurface via two irrelevant parameters. Benefiting from this flexible phase manipulation ability, a vectorial hologram generator and metalens array with spatially varying polarizations were demonstrated. This work provides an effective approach to avoid the pixel and efficiency losses caused by the intrinsic symmetry of the PB geometric phase, and it may play an important role in the miniaturization and integration of multipolarization-involved displays, real-time imaging, and spectroscopy systems. [ABSTRACT FROM AUTHOR]

Over the last decade, researchers have found abnormal expression of transient receptor potential (TRP) channels. In particular, members of the thermally sensitive subclass (thermo-TRPs) are involved in many disease processes. Moreover, they have a vital role in the occurrence and development of gastric cancer (GC). Accordingly, thermo-TRPs constitute a major pharmacological target, and the elucidation of the mechanisms underlying their response to physiological stimuli or drugs is key for notable advances in GC treatment. Therefore, this paper summarizes the existing literature about thermo-TRP protein expression changes that are linked to the incidence and progression of GC. The review also discusses the implication of such association to pathology and cell physiology and identifies potential thermo-TRP protein targets for diagnosis and treatment of GC. [ABSTRACT FROM AUTHOR]

Microalgae are organisms that have the ability to perform photosynthesis, capturing CO2 from the atmosphere to produce different metabolites such as vitamins, sugars, lipids, among others, many of them with different biotechnological applications. Recently, these microorganisms have been widely studied due to their possible use to obtain clean energy. It has been postulated that the growth of microalgae and the production of high-energy metabolites depend on the correct function of cellular organelles such as mitochondria and chloroplasts. Thus, the development of different genetic tools to improve the function of these organelles is of high scientific and technological interest. In this paper we review the recent advances in microalgae engineering and the role of cellular organelles in order to increase cell productivity and biomass. [ABSTRACT FROM AUTHOR]

TP53-induced glycolysis and apoptosis regulator (TIGAR) mainly regulates pentose phosphate pathway by inhibiting glycolysis, so as to synthesize ribose required by DNA, promote DNA damage repair and cell proliferation, maintain cell homeostasis and avoid body injury. Its physiological functions include anti-oxidative stress, reducing inflammation, maintaining mitochondrial function, inhibiting apoptosis, reducing autophagy etc. This paper reviews the research of TIGAR in neurological diseases, including stroke, Parkinson's disease (PD), Alzheimer's disease (AD), seizures and brain tumors, aiming to provide reference for the development of new therapeutic targets. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer in the head and neck region (HNSCC) is exponentially increasing due to human papillomavirus (HPV) infections. This paper helps us to understand the complexity of the inflammatory networks and the mechanisms of immune evasion in HPV+ HNSCC to open up new avenues and drive the discovery of useful tools to be translated clinically in the screening and treatment of these cases, especially to overcome resistance and improve patients' quality of life. Head and neck squamous cell carcinomas (HNSCC) are a heterogeneous group of malignancies which have shown exponential incidence in the last two decades especially due to human papillomavirus (HPV) infection. The HPV family comprises more than 100 types of viruses with HPV16 and HPV18 being the most prevalent strains in HNSCC. Literature data reveal that the mutation profile as well as the response to chemotherapy and radiotherapy are distinct among HPV+ versus HPV-negative tumors. Furthermore, the presence of the virus induces activation of an immune response, in particular the recruitment of specific antiviral T lymphocytes to tumor sites. These T cells when activated produce soluble factors including cytokines and chemokines capable of modifying the local immune tumor microenvironment and impact on tumor response to the treatment. In this comprehensive review we investigated current knowledge on how the presence of an HPV can modify the inflammatory response systemically and within the tumor microenvironment's immunological responses, thereby impacting on disease prognosis and survival. We highlighted the research gaps and emerging approaches necessary to discover novel immunotherapeutic targets for HPV-associated HNSCC. [ABSTRACT FROM AUTHOR]

The number of papers that have investigated the interaction between microglia and pericytes is still relatively low, but recent evidence has demonstrated the importance of the association of pericytes with microglia [[83]]. Keywords: blood-brain barrier; blood vessel; brain development; cortex; endothelial cell; microglia; neurovascular unit; pericyte; vascular structure EN blood-brain barrier blood vessel brain development cortex endothelial cell microglia neurovascular unit pericyte vascular structure 1835 14 11/17/22 20221101 NES 221101 1. Glp1r SP + sp mural cells are largely SMCs, while the majority of Gipr SP + sp mural cells are pericytes, indicating that Gipr may be a useful marker of pericytes [[14]]. A previous study reported that FACS-isolated cells expressing Tbx18, a transcription factor that is selectively expressed in pericytes and vascular SMCs in multiple organs of adult mice, behaved similarly to mesenchymal stem cells in vitro, but lineage tracing experiments using an inducible Tbx18-CreERT2 line revealed that pericytes and vascular SMCs maintained their identity with age and in diverse pathological settings, suggesting that these cell types did not significantly contribute to other cell lineages [[104]]. An in vitro cell culture experiment of microglia and pericytes, which were isolated as NG2 SP + sp PDGFR SP - sp cells, demonstrated that the density of microglia was increased in microglia cultured together with pericytes as compared to microglia cultured alone, suggesting that pericytes promote microglial proliferation. [Extracted from the article]

Leber hereditary optic neuropathy (LHON) is a rare disease with a prevalence of 1 in 25,000 births. LHON usually presents in young males, with painless loss of visual acuity in one or both eyes. Recently an autosomal recessive form of the disease (arLHON or LHONAR) has been described, which is caused by a biallelic mutation in the DNAJC30 gene (usually a missense mutation c.152A>G). The phenotypic and clinical characteristics of patients with arLHON are similar to those of mtLHON, but some differences have been described. Therapy is problematic and challenging. This paper describes clinical and electrophysiological findings in one family (three children and two parents) with arLHON and emphasizes the role of Photopic Negative Response Electroretinography, which provides objective measurement of retinal ganglion cells function. In Leber hereditary optic neuropathy, abnormal retinal ganglion cells function can be found in both eyes, even if visual acuity loss only occurs in one eye. Early clinical diagnosis, confirmed by genetic analysis, may be the key to sight-preserving treatment. [ABSTRACT FROM AUTHOR]

Orthodontic tooth movement (OTM) is a tissue remodeling process based on orthodontic force loading. Compressed periodontal tissues have a complicated aseptic inflammatory cascade, which are considered the initial factor of alveolar bone remodeling. Since skeletal and immune systems shared a wide variety of molecules, osteoimmunology has been generally accepted as an interdisciplinary field to investigate their interactions. Unsurprisingly, OTM is considered a good mirror of osteoimmunology since it involves immune reaction and bone remolding. In fact, besides bone remodeling, OTM involves cementum resorption, soft tissue remodeling, orthodontic pain, and relapse, all correlated with immune cells and/or immunologically active substance. The aim of this paper is to review the interaction of immune system with orthodontic tooth movement, which helps gain insights into mechanisms of OTM and search novel method to short treatment period and control complications. [ABSTRACT FROM AUTHOR]

Simple Summary: Lymphatic metastasis of pancreatic cancer is an important factor leading to poor prognosis of patients. In order to explore the relevant mechanism, we designed research and found that pancreatic cancer cell-derived exosomes promote lymphangiogenesis by downregulating the ABHD11-AS1 expression. This finding provides a new therapeutic strategy for inhibiting lymphatic metastasis metastasis in pancreatic cancer. Research on pancreatic cancer microbiomes has attracted attention in recent years. The current view is that enriched microbial communities in pancreatic cancer tissues may affect pancreatic cancer metastasis, including lymph node (LN) metastasis. Similar to carriers of genetic information between cells, such as DNA, mRNA, protein, and non-coding RNA, exosomes are of great importance in early LN metastasis in tumors, including pancreatic cancer. Our previous study showed that the long non-coding RNA ABHD11-AS1 was highly expressed in tissues of patients with pancreatic cancer, and was correlated with patient survival time. However, the role of ABHD11-AS1 in pancreatic cancer LN metastasis has rarely been studied. Hence, in this paper we confirmed that exosomes derived from pancreatic cancer cells could promote lymphangiogenesis in vitro and in vivo, and that the mechanism was related to the downregulation of ABHD11-AS1 expression in lymphatic endothelial cells, and to the enhancement of their ability to proliferate, migrate, and form tubes. These findings preliminarily show a new mechanism by which pancreatic cancer cells regulate peripheral lymphangiogenesis, providing a new therapeutic strategy for inhibiting LN metastasis in pancreatic cancer. [ABSTRACT FROM AUTHOR]

Food allergy is a serious public health problem because of its high incidence and risk. Probiotics can induce immune regulation in patients with allergic diseases, but its mechanism is not fully clear. In this paper, b-lactoglobulin (bLG)-sensitized mice were used as models to explore the mechanism of Bifidobacterium animalis KV9 (KV9) and Lactobacillus vaginalis FN3 (FN3) on reducing allergic reactions and regulating immune cell function. The results showed that oral administration of KV9 and FN3 significantly reduced the scores of allergic symptoms, hypothermia symptoms, and serum levels of bLG-specific immunoglobulins E (b-LG-sIgE), histamine, and mast cell protease in allergic mice. Flow cytometry analysis of intestinal dendritic cells (DCs) showed that the proportion of CD11c+major histocompatibility complex (MHC)-II+DCs, CD11c+CD80+DCs, and CD11c+ CD86+DCs increased after KV9 and FN3 intervention, indicating that the strains induced immature DCs and decreased the antigen-presenting capacity of DCs. Meanwhile, the toll-like receptor 4 (TLR4)-NF-kB signaling pathway was activated in DCs. The secretion of interleukin-12 (IL-12) was significantly increased, while interleukin-4 (IL-4) was decreased by DCs after KV9 and FN3 intervention, indicating that DCs have the potential to promote T-cell differentiation into T helper type 1 (Th1) cells. Furthermore, the proportion of CD3+CD8−IFN-g+ T cells in the spleen increased, while CD3+CD8−IL-4+T cells decreased after oral administration of KV9 and FN3, correcting the T helper type 2 (Th2)-skewed immune responses. These results indicate that KV9 and FN3 reduce b-LGinduced allergic symptoms in mice, and suggest that the two potential probiotics might be used as an alternative therapeutic agent for mitigating food allergy. [ABSTRACT FROM AUTHOR]

Objective: Infiltration of tumor-associated macrophages is closely linked to the malignant development of human cancers. This research studies the function of C-C motif chemokine ligand 7 (CCL7) in the macrophage accumulation in lung adenocarcinoma (LUAD) and the underpinning mechanism.Methods: The expression profile of CCL7 in LUAD and its correlations with patient's prognosis and macrophage infiltration were predicted via bioinformatics systems. Artificial up- or downregulation of CCL7 was induced in LUAD cells to explore its function in the mobility, EMT of cancer cells, and migration of M2 macrophages. Cancer cells were implanted in NOD/SCID mice to induce xenograft tumors. The CCL7-related transcription factors or factors were predicted by bioinformatic tools, and the molecular interactions were confirmed by immunoprecipitation or luciferase assays.Results: CCL7 was highly expressed in LUAD and linked to increased TAM infiltration. Knockdown of CCL7 suppressed the chemotaxis and M2 skewing of macrophages, and it blocked the EMT and mobility of LUAD cells. CCL7 downregulation also suppressed macrophage infiltration in xenograft tumors in mice. Spi-1 proto-oncogene (SPI1) was confirmed as an upstream factor activating CCL7 transcription, and LINC01094 was found to bind to SPI1 to promote its nuclear translocation. Upregulation of SPI1 restored the chemotactic migration and M2 polarization of macrophages in LUAD cells.Conclusion: This paper reveals that LINC01094 binds to SPI1 to promote its nuclear translocation, which further activates CCL7 transcription by binding to its promoter, leading to M2 macrophage accumulation and dissemination of tumor cells. [ABSTRACT FROM AUTHOR]

Simple Summary: Thyroid cancer is the most common solid tumor of the endocrine glands. The cancer cell contribution to thyroid cancer development and progression has been studied extensively, whereas the involvement of the tumor microenvironment, particularly of cancer-associated fibroblasts (CAFs), in thyroid cancer growth still must be largely analyzed. The tumor microenvironment, comprising molecules, blood and lymphatic tumor vessels and several non cancer stromal cells, such as CAFs, dramatically influences solid tumor growth and therapy resistance. In particular, investigations on CAF contribution to solid tumor growth and therapeutic resistance represent an important area of oncological research. Moreover, studies focused on the role of CAFs in thyroid cancer could lead to a better comprehension of mechanisms regulating cancer growth and to the development of new therapeutic strategies. Therefore, in this paper, we review the hallmarks of CAFs and their role on thyroid cancer. Thyroid cancer is the most common type of endocrine cancer, and its prevalence continue to rise. Non-metastatic thyroid cancer patients are successfully treated. However, looking for new therapeutic strategies is of great importance for metastatic thyroid cancers that still lead to death. With respect to this, the tumor microenvironment (TME), which plays a key role in tumor progression, should be considered as a new promising therapeutic target to hamper thyroid cancer progression. Indeed, thyroid tumors consist of cancer cells and a heterogeneous and ever-changing niche, represented by the TME, which contributes to establishing most of the features of cancer cells. The TME consists of extracellular matrix (ECM) molecules, soluble factors, metabolites, blood and lymphatic tumor vessels and several stromal cell types that, by interacting with each other and with tumor cells, affect TME remodeling, cancer growth and progression. Among the thyroid TME components, cancer-associated fibroblasts (CAFs) have gained more attention in the last years. Indeed, recent important evidence showed that thyroid CAFs strongly sustain thyroid cancer growth and progression by producing soluble factors and ECM proteins, which, in turn, deeply affect thyroid cancer cell behavior and aggressiveness. Hence, in this article, we describe the thyroid TME, focusing on the desmoplastic stromal reaction, which is a powerful indicator of thyroid cancer progression and an invasive growth pattern. In addition, we discuss the origins and features of the thyroid CAFs, their influence on thyroid cancer growth and progression, their role in remodeling the ECM and their immune-modulating functions. We finally debate therapeutic perspectives targeting CAFs. [ABSTRACT FROM AUTHOR]