Dual ifgMosaic: A Versatile Method for Multispectral and Combinatorial Mosaic Gene-Function Analysis.

Improved methods for manipulating and analyzing gene function have provided a better understanding of how genes work during organ development and disease. Inducible functional genetic mosaics can be extraordinarily useful in the study of biological systems; however, this experimental approach is still rarely used in vertebrates. This is mainly due to technical difficulties in the assembly of large DNA constructs carrying multiple genes and regulatory elements and their targeting to the genome. In addition, mosaic phenotypic analysis, unlike classical single gene-function analysis, requires clear labeling and detection of multiple cell clones in the same tissue. Here, we describe several methods for the rapid generation of transgenic or gene-targeted mice and embryonic stem (ES) cell lines containing all the necessary elements for inducible, fluorescent, and functional genetic mosaic (ifgMosaic) analysis. This technology enables the interrogation of multiple and combinatorial gene function with high temporal and cellular resolution.

Arterialization requires the timely suppression of cell growth.

The formation of arteries is thought to occur by the induction of a highly conserved arterial genetic programme in a subset of vessels that will later experience an increase in oxygenated blood flow1,2. The initial steps of arterial specification require both the VEGF and Notch signalling pathways3-5. Here, we combine inducible genetic mosaics and transcriptomics to modulate and define the function of these signalling pathways in cell proliferation, arteriovenous differentiation and mobilization. We show that endothelial cells with high levels of VEGF or Notch signalling are intrinsically biased to mobilize and form arteries; however, they are not genetically pre-determined, and can also form veins. Mechanistically, we found that increased levels of VEGF and Notch signalling in pre-arterial capillaries suppresses MYC-dependent metabolic and cell-cycle activities, and promotes the incorporation of endothelial cells into arteries. Mosaic lineage-tracing studies showed that endothelial cells that lack the Notch-RBPJ transcriptional activator complex rarely form arteries; however, these cells regained the ability to form arteries when the function of MYC was suppressed. Thus, the development of arteries does not require the direct induction of a Notch-dependent arterial differentiation programme, but instead depends on the timely suppression of endothelial cell-cycle progression and metabolism, a process that precedes arterial mobilization and complete differentiation.

Molecular Connectors Boosting the Performance of MoS2 Cathodes in Zinc-Ion Batteries.

Zinc-ion batteries (ZIBs) are promising energy storage systems due to high energy density, low-cost, and abundant availability of zinc as a raw material. However, the greatest challenge in ZIBs research is lack of suitable cathode materials that can reversibly intercalate Zn2+ ions. 2D layered materials, especially MoS2 -based, attract tremendous interest due to large surface area and ability to intercalate/deintercalate ions. Unfortunately, pristine MoS2 obtained by traditional protocols such as chemical exfoliation or hydrothermal/solvothermal methods exhibits limited electronic conductivity and poor chemical stability upon charge/discharge cycling. Here, a novel molecular strategy to boost the electrochemical performance of MoS2 cathode materials for aqueous ZIBs is reported. The use of dithiolated conjugated molecular pillars, that is, 4,4'-biphenyldithiols, enables to heal defects and crosslink the MoS2 nanosheets, yielding covalently bridged networks (MoS2 -SH2) with improved ionic and electronic conductivity and electrochemical performance. In particular, MoS2 -SH2 electrodes display high specific capacity of 271.3 mAh g-1 at 0.1 A g-1 , high energy density of 279 Wh kg-1 , and high power density of 12.3 kW kg-1 . With its outstanding rate capability (capacity of 148.1 mAh g-1 at 10 A g-1 ) and stability (capacity of 179 mAh g-1 after 1000 cycles), MoS2 -SH2 electrodes outperform other MoS2 -based electrodes in ZIBs.

Role of Artificial Intelligence in Colonoscopy Detection of Advanced Neoplasias : A Randomized Trial.

BACKGROUND: The role of computer-aided detection in identifying advanced colorectal neoplasia is unknown. OBJECTIVE: To evaluate the contribution of computer-aided detection to colonoscopic detection of advanced colorectal neoplasias as well as adenomas, serrated polyps, and nonpolypoid and right-sided lesions. DESIGN: Multicenter, parallel, randomized controlled trial. (ClinicalTrials.gov: NCT04673136). SETTING: Spanish colorectal cancer screening program. PARTICIPANTS: 3213 persons with a positive fecal immunochemical test. INTERVENTION: Enrollees were randomly assigned to colonoscopy with or without computer-aided detection. MEASUREMENTS: Advanced colorectal neoplasia was defined as advanced adenoma and/or advanced serrated polyp. RESULTS: The 2 comparison groups showed no significant difference in advanced colorectal neoplasia detection rate (34.8% with intervention vs. 34.6% for controls; adjusted risk ratio [aRR], 1.01 [95% CI, 0.92 to 1.10]) or the mean number of advanced colorectal neoplasias detected per colonoscopy (0.54 [SD, 0.95] with intervention vs. 0.52 [SD, 0.95] for controls; adjusted rate ratio, 1.04 [99.9% CI, 0.88 to 1.22]). Adenoma detection rate also did not differ (64.2% with intervention vs. 62.0% for controls; aRR, 1.06 [99.9% CI, 0.91 to 1.23]). Computer-aided detection increased the mean number of nonpolypoid lesions (0.56 [SD, 1.25] vs. 0.47 [SD, 1.18] for controls; adjusted rate ratio, 1.19 [99.9% CI, 1.01 to 1.41]), proximal adenomas (0.94 [SD, 1.62] vs. 0.81 [SD, 1.52] for controls; adjusted rate ratio, 1.17 [99.9% CI, 1.03 to 1.33]), and lesions of 5 mm or smaller (polyps in general and adenomas and serrated lesions in particular) detected per colonoscopy. LIMITATIONS: The high adenoma detection rate in the control group may limit the generalizability of the findings to endoscopists with low detection rates. CONCLUSION: Computer-aided detection did not improve colonoscopic identification of advanced colorectal neoplasias. PRIMARY FUNDING SOURCE: Medtronic.

Assessment of Untargeted Metabolomics by Hydrophilic Interaction Liquid Chromatography-Mass Spectrometry to Define Breast Cancer Liquid Biopsy-Based Biomarkers in Plasma Samples.

An early diagnosis of cancer is fundamental not only in regard to reducing its mortality rate but also in terms of counteracting the progression of the tumor in the initial stages. Breast cancer (BC) is the most common tumor pathology in women and the second deathliest cancer worldwide, although its survival rate is increasing thanks to improvements in screening programs. However, the most common techniques to detect a breast tumor tend to be time-consuming, unspecific or invasive. Herein, the use of untargeted hydrophilic interaction liquid chromatography-mass spectrometry analysis appears as an analytical technique with potential use for the early detection of biomarkers in liquid biopsies from BC patients. In this research, plasma samples from 134 BC patients were compared with 136 from healthy controls (HC), and multivariate statistical analyses showed a clear separation between four BC phenotypes (LA, LB, HER2, and TN) and the HC group. As a result, we identified two candidate biomarkers that discriminated between the groups under study with a VIP > 1 and an AUC of 0.958. Thus, targeting the specific aberrant metabolic pathways in future studies may allow for better molecular stratification or early detection of the disease.

Pitahaya (Hylocereus ocamponis)-Peel and -Flesh Flour Obtained from Fruit Co-Products-Assessment of Chemical, Techno-Functional and In Vitro Antioxidant Properties.

The aim of this work was to assess the chemical composition and physico-chemical, techno-functional, and in vitro antioxidant properties of flours obtained from the peel and flesh of pitahaya (Hylocereus ocamponis) to determine their potential for use as ingredients for food enrichment. The chemical composition, including total betalains, mineral content, and polyphenolic profile, was determined. The techno-functional properties (water holding, oil holding, and swelling capacities) were also evaluated. For the antioxidant capacity, four different methodologies, namely ferrous ion-chelating ability assay, ferric-reducing antioxidant power assay; 1,1-Diphenyl-2-picrylhydrazyl radical scavenging ability assay, and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical assay, were used. Pitahaya-peel flour had higher values for protein (6.72 g/100 g), ash (11.63 g/100 g), and dietary fiber 56.56 g/100 g) than pitahaya-flesh flour, with values of 6.06, 3.63, and 8.22 g/100 g for protein, ash, and dietary fiber, respectively. In the same way, pitahaya peel showed a higher content of minerals, betalains, and polyphenolic compounds than pitahaya-flesh flour, with potassium (4.43 g/100 g), catechin (25.85 mg/g), quercetin-3-rhamnoside (11.66 mg/g) and myricetrin (12.10 mg/g) as principal compounds found in the peel. Again, pitahaya-peel flour showed better techno-functional and antioxidant properties than pitahaya-flesh flour. The results obtained suggest that the flours obtained from the peel and pulp of pitahaya (H. ocamponis) constitute a potential material to be utilized as an ingredient in the food industry due to the high content of bioactive compounds such as betalains, phenolic acids, and flavonoids, with notable antioxidant capacity.

Maternal hepatocytes heterogeneously and dynamically exhibit developmental phenotypes partially via yes-associated protein 1 during pregnancy.

Pregnancy induces reprogramming of maternal physiology to support fetal development and growth. Maternal hepatocytes undergo hypertrophy and hyperplasia to drive maternal liver growth and alter their gene expression profiles simultaneously. This study aimed to further understand maternal hepatocyte adaptation to pregnancy. Timed pregnancies were generated in mice. In a nonpregnant state, most hepatocytes expressed Cd133, α-fetal protein (Afp) and epithelial cell adhesion molecule (Epcam) mRNAs, whereas overall, at the protein level, they exhibited a CD133-/AFP- phenotype; however, pericentral hepatocytes were EpCAM+. As pregnancy advanced, although most maternal hepatocytes retained Cd133, Afp, and Epcam mRNA expression, they generally displayed a phenotype of CD133+/AFP+, and EpCAM protein expression was switched from pericentral to periportal maternal hepatocytes. In addition, we found that the Hippo/yes-associated protein (YAP) pathway does not respond to pregnancy. Yap1 gene deletion specifically in maternal hepatocytes did not affect maternal liver growth or metabolic zonation. However, the absence of Yap1 gene eliminated CD133 protein expression without interfering with Cd133 transcript expression in maternal livers. We demonstrated that maternal hepatocytes acquire heterogeneous and dynamic developmental phenotypes, resembling fetal hepatocytes, partially via YAP1 through a posttranscriptional mechanism. Moreover, maternal liver is a new source of AFP. In addition, maternal liver grows and maintains its metabolic zonation independent of the Hippo/YAP1 pathway. Our findings revealed a novel and gestation-dependent phenotypic plasticity in adult hepatocytes.NEW & NOTEWORTHY We found that maternal hepatocytes exhibit developmental phenotypes in a temporal and spatial manner, similarly to fetal hepatocytes. They acquire this new property partially via yes-associated protein 1.

Analysis of the Differential Efficacy of the Reduced Version Over the Extended Version of an Affective-Sexual Education Program for Adults with Intellectual Disabilities.

Recently, with the increase in demand, multiple intervention proposals aimed at improving the sexual health of people with intellectual disabilities have emerged. Among them is the SALUDIVERSEX program, which takes a positive approach to sexuality. It has an extended version, consisting of 16 sessions and whose efficacy has already been proven, and a reduced version of 10 sessions. Thus, the present study aimed to test the differential efficacy of the two versions. A total of 208 participants (103 women and 105 men) aged between 19 and 67 years (M = 37.23, SD = 10.66) completed a battery of instruments before and after the intervention. Statistical analyses showed that users who participated in the reduced version of the program presented a significantly higher rate of improvement in their sexual behaviors compared to those who participated in the extended version (Sexual response: ß10 = - 0.46 ± 0.19, p = .034; Sex practices: ß10 = - 0.52 ± 0.23, p = .037; Use condoms: ß10 = - 1.56 ± 0.59, p = .017), as well as a significantly higher decrease in the risk of suffering sexual abuse (ß10 = 3.95 ± 0.64, p < .001). However, no statistically significant differences in sexuality knowledge were obtained with respect to the improvement between the two versions (ß10 = - 0.09 ± 1.21, p = .94). Meanwhile, the professionals who applied the program found that those who participated in the reduced version, although they presented a significantly greater increase in their knowledge about privacy (ß10 = - 0.48 ± 0.08, p < .001), did not improve their concerns about their inappropriate sexual behaviors as much as the users of the extended version (ß10 = - 1.35 ± 0.21, p < .001). Thus, although both versions were effective, the reduced version seems to do so to a greater extent and in a shorter time, which makes it the more recommendable option.

A New COVID-19 Detection Method Based on CSK/QAM Visible Light Communication and Machine Learning.

This article proposes a novel method for detecting coronavirus disease 2019 (COVID-19) in an underground channel using visible light communication (VLC) and machine learning (ML). We present mathematical models of COVID-19 Deoxyribose Nucleic Acid (DNA) gene transfer in regular square constellations using a CSK/QAM-based VLC system. ML algorithms are used to classify the bands present in each electrophoresis sample according to whether the band corresponds to a positive, negative, or ladder sample during the search for the optimal model. Complexity studies reveal that the square constellation N=22i×22i,(i=3) yields a greater profit. Performance studies indicate that, for BER = 10-3, there are gains of -10 [dB], -3 [dB], 3 [dB], and 5 [dB] for N=22i×22i,(i=0,1,2,3), respectively. Based on a total of 630 COVID-19 samples, the best model is shown to be XGBoots, which demonstrated an accuracy of 96.03%, greater than that of the other models, and a recall of 99% for positive values.

User Experience Design for Social Robots: A Case Study in Integrating Embodiment.

Social robotics is an emerging field with a high level of innovation. For many years, it was a concept framed in the literature and theoretical approaches. Scientific and technological advances have made it possible for robots to progressively make their way into different areas of our society, and now, they are ready to make the leap out of the industry and extend their presence into our daily lives. In this sense, user experience plays a fundamental role in achieving a smooth and natural interaction between robots and humans. This research focused on the user experience approach in terms of the embodiment of a robot, centring on its movements, gestures, and dialogues. The aim was to investigate how the interaction between robotic platforms and humans takes place and what differential aspects should be considered when designing the robot tasks. To achieve this objective, a qualitative and quantitative study was conducted based on a real interview between several human users and the robotic platform. The data were gathered by recording the session and having each user complete a form. The results showed that participants generally enjoyed interacting with the robot and found it engaging, which led to greater trust and satisfaction. However, delays and errors in the robot's responses caused frustration and disconnection. The study found that incorporating embodiment into the design of the robot improved the user experience, and the robot's personality and behaviour were significant factors. It was concluded that robotic platforms and their appearance, movements, and way of communicating have a decisive influence on the user's opinion and the way they interact.

Beyond the Clinic: The Activation of Diverse Cellular and Humoral Factors Shapes the Immunological Status of Patients with Active Tuberculosis.

Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis (TB), has killed nearly one billion people in the last two centuries. Nowadays, TB remains a major global health problem, ranking among the thirteen leading causes of death worldwide. Human TB infection spans different levels of stages: incipient, subclinical, latent and active TB, all of them with varying symptoms, microbiological characteristics, immune responses and pathologies profiles. After infection, Mtb interacts with diverse cells of both innate and adaptive immune compartments, playing a crucial role in the modulation and development of the pathology. Underlying TB clinical manifestations, individual immunological profiles can be identified in patients with active TB according to the strength of their immune responses to Mtb infection, defining diverse endotypes. Those different endotypes are regulated by a complex interaction of the patient's cellular metabolism, genetic background, epigenetics, and gene transcriptional regulation. Here, we review immunological categorizations of TB patients based on the activation of different cellular populations (both myeloid and lymphocytic subsets) and humoral mediators (such as cytokines and lipid mediators). The analysis of the participating factors that operate during active Mtb infection shaping the immunological status or immune endotypes of TB patients could contribute to the development of Host Directed Therapy.

SALUDIVERSEX: A quality of life and sexual health intervention for adults with mild intellectual disabilities.

Individuals with intellectual disabilities need an affective and sexual education adapted to their characteristics. There are few interventions that meet these objectives and offer empirical evidence of their efficacy. To respond to the limitations of existing interventions, an evidence-based affective-sexual educational intervention for adults with a mild degree of intellectual disability is proposed: SALUDIVERSEX. Participants will be randomly assigned to an intervention group that will receive the SALUDIVERSEX program or to a waiting list group. The intervention will be implemented by educators of occupational centers after a thorough training phase. Our main hypothesis is that the SALUDIVERSEX program will improve the sexual health and quality of life, through the joint action built into three components: the acquisition of basic information, the development of skills and strategies and the achievement of healthy attitudes towards the experience and expression of sexuality. The results of this approach could have important implications for optimizing the quality of life and self-determination of individuals with Intellectual disability by contributing to the development of healthy sexuality.

Supramolecular Engineering of Cathode Materials for Aqueous Zinc-ion Energy Storage Devices: Novel Benzothiadiazole Functionalized Two-Dimensional Olefin-Linked COFs.

Two-dimensional covalent organic frameworks (COFs) have emerged as promising materials for energy storage applications exhibiting enhanced electrochemical performance. While most of the reported organic cathode materials for zinc-ion batteries use carbonyl groups as electrochemically-active sites, their high hydrophilicity in aqueous electrolytes represents a critical drawback. Herein, we report a novel and structurally robust olefin-linked COF-TMT-BT synthesized via the aldol condensation between 2,4,6-trimethyl-1,3,5-triazine (TMT) and 4,4'-(benzothiadiazole-4,7-diyl)dibenzaldehyde (BT), where benzothiadiazole units are explored as novel electrochemically-active groups. Our COF-TMT-BT exhibits an outstanding Zn2+ storage capability, delivering a state-of-the-art capacity of 283.5 mAh g-1 at 0.1 A g-1 . Computational and experimental analyses reveal that the charge-storage mechanism in COF-TMT-BT electrodes is based on the supramolecularly engineered and reversible Zn2+ coordination by the benzothiadiazole units.

New Anderson-Based Polyoxometalate Covalent Organic Frameworks as Electrodes for Energy Storage Boosted Through Keto-Enol Tautomerization.

The unique electrochemical properties of polyoxometalates (POMs) render them ideal components for the fabrication of next-generation high-performance energy storage systems. However, their practical applications have been hindered by their high solubility in common electrolytes. This problem can be overcome by the effective hybridization of POMs with other materials. Here we present the design and synthesis of two novel polyoxometalate-covalent organic frameworks (POCOF) via one-pot solvothermal strategy between an amino-functionalized Anderson-type POM and a trialdehyde-based building unit. We show that structural and functional complexity can be enriched by adding hydroxyl groups in the 2,4,6 position to the benzene-1,3,5-tricarbaldehyde allowing to exploit for the first time in POCOFs the keto-enol tautomerization as additional feature to impart greater chemical stability to the COFs and enhanced properties leading to large specific surface area (347 m2 /g) and superior electrochemical performance of the POCOF-1 electrodes, when compared with POCOF-2 electrodes that possess only imine-type linkage and with pristine POM electrodes. Specifically, POCOF-1 electrodes display remarkable specific, areal, and volumetric capacitance (125 F/g, 248 mF/cm2 and 41.9 mF/cm3 , respectively) at a current density of 0.5 A/g, a maximum energy density (56.2 Wh/kg), a maximum power density (3.7 kW/kg) and an outstanding cyclability (90 % capacitance retention after 5000 cycles).

Selective Ion Sensing in Artificial Sweat Using Low-Cost Reduced Graphene Oxide Liquid-Gated Plastic Transistors.

Health monitoring is experiencing a radical shift from clinic-based to point-of-care and wearable technologies, and a variety of nanomaterials and transducers have been employed for this purpose. 2D materials (2DMs) hold enormous potential for novel electronics, yet they struggle to meet the requirements of wearable technologies. Here, aiming to foster the development of 2DM-based wearable technologies, reduced graphene oxide (rGO)-based liquid-gated transistors (LGTs) for cation sensing in artificial sweat endowed with distinguished performance and great potential for scalable manufacturing is reported. Laser micromachining is employed to produce flexible transistor test patterns employing rGO as the electronic transducer. Analyte selectivity is achieved by functionalizing the transistor channel with ion-selective membranes (ISMs) via a simple casting method. Real-time monitoring of K+ and Na+ in artificial sweat is carried out employing a gate voltage pulsed stimulus to take advantage of the fast responsivity of rGO. The sensors show excellent selectivity toward the target analyte, low working voltages (<0.5 V), fast (5-15 s), linear response at a wide range of concentrations (10 µm to 100 mm), and sensitivities of 1 µA/decade. The reported strategy is an important step forward toward the development of wearable sensors based on 2DMs for future health monitoring technologies.

Prospective associations between a priori dietary patterns adherence and kidney function in an elderly Mediterranean population at high cardiovascular risk.

PURPOSE: To assess the association between three different a priori dietary patterns adherence (17-item energy reduced-Mediterranean Diet (MedDiet), Trichopoulou-MedDiet and Dietary Approach to Stop Hypertension (DASH)), as well as the Protein Diet Score and kidney function decline after one year of follow-up in elderly individuals with overweight/obesity and metabolic syndrome (MetS). METHODS: We prospectively analyzed 5675 participants (55-75 years) from the PREDIMED-Plus study. At baseline and at one year, we evaluated the creatinine-based estimated glomerular filtration rate (eGFR) and food-frequency questionnaires-derived dietary scores. Associations between four categories (decrease/maintenance and tertiles of increase) of each dietary pattern and changes in eGFR (ml/min/1.73m2) or ≥ 10% eGFR decline were assessed by fitting multivariable linear or logistic regression models, as appropriate. RESULTS: Participants in the highest tertile of increase in 17-item erMedDiet Score showed higher upward changes in eGFR (ß: 1.87 ml/min/1.73m2; 95% CI: 1.00-2.73) and had lower odds of ≥ 10% eGFR decline (OR: 0.62; 95% CI: 0.47-0.82) compared to individuals in the decrease/maintenance category, while Trichopoulou-MedDiet and DASH Scores were not associated with any renal outcomes. Those in the highest tertile of increase in Protein Diet Score had greater downward changes in eGFR (ß: - 0.87 ml/min/1.73m2; 95% CI: - 1.73 to - 0.01) and 32% higher odds of eGFR decline (OR: 1.32; 95% CI: 1.00-1.75). CONCLUSIONS: Among elderly individuals with overweight/obesity and MetS, only higher upward change in the 17-item erMedDiet score adherence was associated with better kidney function after one year. However, increasing Protein Diet Score appeared to have an adverse impact on kidney health. TRIAL REGISTRATION NUMBER: ISRCTN89898870 (Data of registration: 2014).

Airflow Analysis in the Context of Sleep Apnea.

The airflow (AF) is a physiological signal involved in the overnight polysomnography (PSG) that reflects the respiratory activity. This signal is able to show the particularities of sleep apnea and is therefore used to define apneic events. In this regard, a growing number of studies have shown the usefulness of employing the overnight airflow as the only or combined information source for diagnosing sleep apnea in both children and adults. Due to its easy acquisition and interpretation, this biosignal has been widely analyzed by means of different signal processing techniques. In this chapter, we review the main methodological approaches applied to characterize and extract relevant information from this signal. In view of the results, we can conclude that the overnight airflow successfully reflects the particularities caused by the occurrence of apneic and hypopneic events and provides useful information for obtaining relevant biomarkers that characterize this disease.

Conventional Machine Learning Methods Applied to the Automatic Diagnosis of Sleep Apnea.

The overnight polysomnography shows a range of drawbacks to diagnose obstructive sleep apnea (OSA) that have led to the search for artificial intelligence-based alternatives. Many classic machine learning methods have been already evaluated for this purpose. In this chapter, we show the main approaches found in the scientific literature along with the most used data to develop the models, useful and large easily available databases, and suitable methods to assess performances. In addition, a range of results from selected studies are presented as examples of these methods. Very high diagnostic performances are reported in these results regardless of the approaches taken. This leads us to conclude that conventional machine learning methods are useful techniques to develop new OSA diagnosis simplification proposals and to act as benchmark for other more recent methods such as deep learning.

Chemical sensing with Au and Ag nanoparticles.

Noble metal nanoparticles (NPs) are ideal scaffolds for the fabrication of sensing devices because of their high surface-to-volume ratio combined with their unique optical and electrical properties which are extremely sensitive to changes in the environment. Such characteristics guarantee high sensitivity in sensing processes. Metal NPs can be decorated with ad hoc molecular building blocks which can act as receptors of specific analytes. By pursuing this strategy, and by taking full advantage of the specificity of supramolecular recognition events, highly selective sensing devices can be fabricated. Besides, noble metal NPs can also be a pivotal element for the fabrication of chemical nose/tongue sensors to target complex mixtures of analytes. This review highlights the most enlightening strategies developed during the last decade, towards the fabrication of chemical sensors with either optical or electrical readout combining high sensitivity and selectivity, along with fast response and full reversibility, with special attention to approaches that enable efficient environmental and health monitoring.

IKKα Induces Epithelial-Mesenchymal Changes in Mouse Skin Carcinoma Cells That Can Be Partially Reversed by Apigenin.

NMSC (non-melanoma skin cancer) is a common tumor in the Caucasian population, accounting for 90% of skin cancers. Among them, squamous cell carcinomas (SCCs) can metastasize and, due to its high incidence, constitute a severe health problem. It has been suggested that cutaneous SCCs with more risk to metastasize express high levels of nuclear IKKα. However, the molecular mechanisms that lead to this enhanced aggressiveness are largely unknown. To understand in depth the influence of nuclear IKKα in skin SCC progression, we have generated murine PDVC57 skin carcinoma cells expressing exogenous IKKα either in the nucleus or in the cytoplasm to further distinguish the tumor properties of IKKα in both localizations. Our results show that IKKα promotes changes in both subcellular compartments, resembling EMT (epithelial-mesenchymal transition), which are more pronounced when IKKα is in the nucleus of these tumor cells. These EMT-related changes include a shift toward a migratory phenotype and induction of the expression of proteins involved in cell matrix degradation, cell survival and resistance to apoptosis. Additionally, we have found that apigenin, a flavonoid with anti-cancer properties, inhibits the expression of IKKα and attenuates most of the pro-tumoral EMT changes induced by IKKα in mouse tumor keratinocytes. Nevertheless, we have found that apigenin only inhibits the expression of the IKKα protein when it is localized in the cytoplasm.