ZFP207 sustains pluripotency by coordinating OCT4 stability, alternative splicing and RNA export.

The pluripotent state is not solely governed by the action of the core transcription factors OCT4, SOX2, and NANOG, but also by a series of co-transcriptional and post-transcriptional events, including alternative splicing (AS) and the interaction of RNA-binding proteins (RBPs) with defined subpopulations of RNAs. Zinc Finger Protein 207 (ZFP207) is an essential transcription factor for mammalian embryonic development. Here, we employ multiple functional analyses to characterize its role in mouse embryonic stem cells (ESCs). We find that ZFP207 plays a pivotal role in ESC maintenance, and silencing of Zfp207 leads to severe neuroectodermal differentiation defects. In striking contrast to human ESCs, mouse ZFP207 does not transcriptionally regulate neuronal and stem cell-related genes but exerts its effects by controlling AS networks and by acting as an RBP. Our study expands the role of ZFP207 in maintaining ESC identity, and underscores the functional versatility of ZFP207 in regulating neural fate commitment.

Mediterranean diet adherence and glycemic control in children and adolescents with type 1 diabetes.

To effectively manage type 1 diabetes (T1D) insulin is essential, with dosages based on lifestyle. The Mediterranean diet has demonstrated its advantages in preventing and enhancing the management of chronic diseases. Our objective was to investigate the potential mediation of sensor activity on the relationship between adherence to the Mediterranean diet and glycemic control in children and adolescents. A total of 150 children and adolescents (mean age = 13.09, SD = 3.54; 44% female) with T1D were recruited. Adherence to the Mediterranean diet was assessed using the KIDMED questionnaire which evaluates 16 items and gives higher scores when adherence is higher. Glycemic control and the duration of sensor activity were evaluated with data from flash glucose monitoring. The data confirmed our hypothesis by revealing that adherence to the Mediterranean diet positively influenced glycemic control (direct effect = 1.505; P < 0.01) and that this relationship was mediated by the duration of sensor activity (indirect effect = 0.531; P < 0.01).  Conclusions: Our results support the increased utilization of glycemic control devices, as they contribute to improve glycemic control and mediate on the positive relationship between adherence to the Mediterranean diet and adequate glycemic control. Furthermore, our findings highlight the importance of incorporating Mediterranean diet recommendations to achieve better glycemic control in children and adolescents with T1D. What is Known: • The Mediterranean diet and glycemic control have proven benefits in improving cardiovascular health in the general population. Scarce evidence exists of these benefits among children and adolescents with T1D. What is New: • Adherence to the Mediterranean diet and greater use of glucose monitoring devices in children and adolescents with T1D are related to better glycemic control. These variables can be enhanced by psychoeducational interventions such as structured diabetes education programs or peer group-based sessions, which highlights the importance of focusing on these aspects.

Charting a path to health: The empowering influence of self-efficacy for the self-management of type 1 diabetes in children and adolescents.

Type 1 diabetes (T1D) in children and adolescents requires a lifelong commitment to disease control, which involves insulin treatment and constant blood glucose monitoring. Framed by Albert Bandura's self-efficacy theory, we focused on analysing the impact of domain-specific self-efficacy for T1D control in children and adolescents and its relationship with different indicators of glycaemic control over time. The study included 205 participants (56.1% male), including 51.7% children and 48.3% adolescents aged 6-18 (M = 13.27, SD = 3.66) years in four longitudinal phases (6 months between phases). The results revealed that higher self-efficacy predicted better health outcomes, with more time spent actively monitoring glucose and more time in the target range. The positive effect of self-efficacy was observed to be maintained over time. This study underscores the importance of taking into account the developmental timing in the onset of T1D. There was a significant relationship between self-efficacy and glucose indicators in adolescents. Although their glucose indicators were worse, self-efficacy became more relevant as they moved from parental management to the self-management of T1D. Implications of the results show the positive effect of self-efficacy on health per glucose indicators, thus suggesting interventions that promote self-efficacy in this population.

Immunomodulatory effects of inactivated Ligilactobacillus salivarius CECT 9609 on respiratory epithelial cells.

The microbiota in humans and animals play crucial roles in defense against pathogens and offer a promising natural source for immunomodulatory products. However, the development of physiologically relevant model systems and protocols for testing such products remains challenging. In this study, we present an experimental condition where various natural products derived from the registered lactic acid bacteria Ligilactobacillus salivarius CECT 9609, known for their immunomodulatory activity, were tested. These products included live and inactivated bacteria, as well as fermentation products at different concentrations and culture times. Using our established model system, we observed no morphological changes in the airway epithelium upon exposure to Pasteurella multocida, a common respiratory pathogen. However, early molecular changes associated with the innate immune response were detected through transcript analysis. By employing diverse methodologies ranging from microscopy to next-generation sequencing (NGS), we characterized the interaction of these natural products with the airway epithelium and their potential beneficial effects in the presence of P. multocida infection. In particular, our discovery highlights that among all Ligilactobacillus salivarius CECT 9609 products tested, only inactivated cells preserve the conformation and morphology of respiratory epithelial cells, while also reversing or altering the natural immune responses triggered by Pasteurella multocida. These findings lay the groundwork for further exploration into the protective role of these bacteria and their derivatives.

Aryl hydrocarbon receptor controls skin homeostasis, regeneration, and hair follicle cycling by adjusting epidermal stem cell function.

Skin integrity requires constant maintenance of a quiescent, yet responsive, population of stem cells. While interfollicular epidermal progenitors control normal homeostasis, hair follicle stem cells residing within the bulge provide regenerative potential during hair cycle and in response to wounding. The aryl hydrocarbon receptor (AhR) modulates cell plasticity and differentiation and its overactivation results in severe skin lesions in humans. However, its physiological role in skin homeostasis and hair growth is unknown. Reconstitution assays grafting primary keratinocytes and dermal fibroblasts into nude mice and 3-D epidermal equivalents revealed a positive role for AhR in skin regeneration, epidermal differentiation, and stem cell maintenance. Furthermore, lack of receptor expression in AhR-/- mice delayed morphogenesis and impaired hair regrowth with a phenotype closely correlating with a reduction in suprabasal bulge stem cells (α6low CD34+ ). Moreover, RNA-microarray and RT-qPCR analyses of fluorescence-activated cell sorting (FACS)-isolated bulge stem cells revealed that AhR depletion impaired transcriptional signatures typical of both epidermal progenitors and bulge stem cells but upregulated differentiation markers likely compromising their undifferentiated phenotype. Altogether, our findings support that AhR controls skin regeneration and homeostasis by ensuring epidermal stem cell identity and highlights this receptor as potential target for the treatment of cutaneous pathologies.

p53 regulation by MDM2 contributes to self-renewal and differentiation of basal stem cells in mouse and human airway epithelium.

Proper physiological function of mammalian airways requires the differentiation of basal stem cells into secretory or multiciliated cells, among others. In addition, the self-renewal ability of these basal stem cells is crucial for developing a quick response to toxic agents in order to re-establish the epithelial barrier function of the airways. Although these epithelial missions are vital, little is known about those mechanism controlling airway epithelial regeneration in health and disease. p53 has been recently proposed as the guardian of homeostasis, promoting differentiation programs, and antagonizing a de-differentiation program. Here, we exploit mouse and human tracheal epithelial cell culture models to study the role of MDM2-p53 signaling in self-renewal and differentiation in the airway epithelium. We show that p53 protein regulation by MDM2 is crucial for basal stem cell differentiation and to keep proper cell proliferation. Therefore, we suggest that MDM2/p53 interaction modulation is a potential target to control regeneration of the mammalian airway epithelia without massively affecting the epithelium integrity and differentiation potential.

Centriole planar polarity assessment in Drosophila wings.

In vertebrates, planar polarization of ciliary basal bodies has been associated with actin polymerization that occurs downstream of the Frizzled-planar cell polarity (Fz-PCP) pathway. In Drosophila wing epithelial cells, which do not have cilia, centrioles also polarize in a Fz-PCP-dependent manner, although the relationship with actin polymerization remains unknown. By combining existing and new quantitative methods, we unexpectedly found that known PCP effectors linked to actin polymerization phenotypes affect neither final centriole polarization nor apical centriole distribution. But actin polymerization is required upstream of Fz-PCP to maintain the centrioles in restricted areas in the apical-most planes of those epithelial cells before and after the actin-based hair is formed. Furthermore, in the absence of proper core Fz-PCP signalling, actin polymerization is insufficient to drive this off-centred centriole migration. Altogether, the results reveal that there are at least two pathways controlling centriole positioning in Drosophila pupal wings - an upstream actin-dependent mechanism involved in centriole distribution that is PCP independent, and an unknown mechanism that links core Fz-PCP and centriole polarization.

Distribution of planar cell polarity proteins in the developing avian retina.

Planar cell polarity (PCP) is evolutionary conserved and play a critical role in proper tissue development and function. During central nervous system development, PCP proteins exhibit specific patterns of distribution and are indispensable for axonal growth, dendritogenesis, neuronal migration, and neuronal differentiation. The retina constitutes an excellent model in which to study molecular mechanisms involved in neural development. The analysis of the spatiotemporal expression of PCP proteins in this model constitutes an useful histological approach in order to identify possible roles of these proteins in retinogenesis. Immunohistochemical techniques revealed that Frz6, Celsr1, Vangl1, Pk1, Pk3, and Fat1 were present in emerging axons from recently differentiated ganglion cells in the chicken retina. Except for Vangl1, they were also asymmetrically distributed in differentiated amacrine cells. Pk1 and Pk3 were restricted in the outer nuclear layer to the outer segment of photoreceptors. Vangl1 was also located in the cell somata of Müller glia. Given these findings together, the distribution of PCP proteins in the developing chicken retina suggest essential roles in axonal guidance during early retinogenesis and a possible involvement in the establishment of cell asymmetry and maintenance of retinal cell phenotypes.

Bmi1 regulates murine intestinal stem cell proliferation and self-renewal downstream of Notch.

Genetic data indicate that abrogation of Notch-Rbpj or Wnt-ß-catenin pathways results in the loss of the intestinal stem cells (ISCs). However, whether the effect of Notch is direct or due to the aberrant differentiation of the transit-amplifying cells into post-mitotic goblet cells is unknown. To address this issue, we have generated composite tamoxifen-inducible intestine-specific genetic mouse models and analyzed the expression of intestinal differentiation markers. Importantly, we found that activation of ß-catenin partially rescues the differentiation phenotype of Rbpj deletion mutants, but not the loss of the ISC compartment. Moreover, we identified Bmi1, which is expressed in the ISC and progenitor compartments, as a gene that is co-regulated by Notch and ß-catenin. Loss of Bmi1 resulted in reduced proliferation in the ISC compartment accompanied by p16(INK4a) and p19(ARF) (splice variants of Cdkn2a) accumulation, and increased differentiation to the post-mitotic goblet cell lineage that partially mimics Notch loss-of-function defects. Finally, we provide evidence that Bmi1 contributes to ISC self-renewal.

Alu retrotransposons promote differentiation of human carcinoma cells through the aryl hydrocarbon receptor.

Cell differentiation is a central process in development and in cancer growth and dissemination. OCT4 (POU5F1) and NANOG are essential for cell stemness and pluripotency; yet, the mechanisms that regulate their expression remain largely unknown. Repetitive elements account for almost half of the Human Genome; still, their role in gene regulation is poorly understood. Here, we show that the dioxin receptor (AHR) leads to differentiation of human carcinoma cells through the transcriptional upregulation of Alu retrotransposons, whose RNA transcripts can repress pluripotency genes. Despite the genome-wide presence of Alu elements, we provide evidences that those located at the NANOG and OCT4 promoters bind AHR, are transcribed by RNA polymerase-III and repress NANOG and OCT4 in differentiated cells. OCT4 and NANOG repression likely involves processing of Alu-derived transcripts through the miRNA machinery involving the Microprocessor and RISC. Consistently, stable AHR knockdown led to basal undifferentiation, impaired Alus transcription and blockade of OCT4 and NANOG repression. We suggest that transcripts produced from AHR-regulated Alu retrotransposons may control the expression of stemness genes OCT4 and NANOG during differentiation of carcinoma cells. The control of discrete Alu elements by specific transcription factors may have a dynamic role in genome regulation under physiological and diseased conditions.

Basolateral sorting of the coxsackie and adenovirus receptor through interaction of a canonical YXXPhi motif with the clathrin adaptors AP-1A and AP-1B.

The coxsackie and adenovirus receptor (CAR) plays key roles in epithelial barrier function at the tight junction, a localization guided in part by a tyrosine-based basolateral sorting signal, (318)YNQV(321). Sorting motifs of this type are known to route surface receptors into clathrin-mediated endocytosis through interaction with the medium subunit (µ2) of the clathrin adaptor AP-2, but how they guide new and recycling membrane proteins basolaterally is unknown. Here, we show that YNQV functions as a canonical YxxΦ motif, with both Y318 and V321 required for the correct basolateral localization and biosynthetic sorting of CAR, and for interaction with a highly conserved pocket in the medium subunits (µ1A and µ1B) of the clathrin adaptors AP-1A and AP-1B. Knock-down experiments demonstrate that AP-1A plays a role in the biosynthetic sorting of CAR, complementary to the role of AP-1B in basolateral recycling of this receptor. Our study illustrates how two clathrin adaptors direct basolateral trafficking of a plasma membrane protein through interaction with a canonical YxxΦ motif.

Dioxin receptor and SLUG transcription factors regulate the insulator activity of B1 SINE retrotransposons via an RNA polymerase switch.

Complex genomes utilize insulators and boundary elements to help define spatial and temporal gene expression patterns. We report that a genome-wide B1 SINE (Short Interspersed Nuclear Element) retrotransposon (B1-X35S) has potent intrinsic insulator activity in cultured cells and live animals. This insulation is mediated by binding of the transcription factors dioxin receptor (AHR) and SLUG (SNAI2) to consensus elements present in the SINE. Transcription of B1-X35S is required for insulation. While basal insulator activity is maintained by RNA polymerase (Pol) III transcription, AHR-induced insulation involves release of Pol III and engagement of Pol II transcription on the same strand. B1-X35S insulation is also associated with enrichment of heterochromatin marks H3K9me3 and H3K27me3 downstream of B1-X35S, an effect that varies with cell type. B1-X35S binds parylated CTCF and, consistent with a chromatin barrier activity, its positioning between two adjacent genes correlates with their differential expression in mouse tissues. Hence, B1 SINE retrotransposons represent genome-wide insulators activated by transcription factors that respond to developmental, oncogenic, or toxicological stimuli.

Unravelling the effect of control agents on Gnomoniopsis smithogilvyi on a chestnut-based medium by proteomics.

BACKGROUND: Gnomoniopsis smithogilvyi is the major chestnut pathogen, responsible for economic losses and recently described as a 3-nitropropionic acid and diplodiatoxin mycotoxin producer. Bacillus amyloliquefaciens QST 713 (Serenade® ASO), B. amyloliquefaciens CIMO-BCA1, and the fungicide Horizon® (tebuconazole) have been shown to reduce the growth of G. smithogilvyi. However, they enhanced mycotoxin production. Proteomics can clarify the mould's physiology and the impact of antifungal agents on the mould's metabolism. Thus, the aim of this study was to assess the impact of Horizon®, Serenade®, and B. amyloliquefaciens CIMO-BCA1 in the proteome of G. smithogilvyi to unveil their modes of action and decipher why the mould responds by increasing the mycotoxin production. For this, the mycelium close to the inhibition zone provoked by antifungals was macroscopically and microscopically observed. Proteins were extracted and analysed using a Q-Exactive plus Orbitrap. RESULTS: The results did not elucidate specific proteins involved in the mycotoxin biosynthesis, but these agents provoked different kinds of stress on the mould, mainly affecting the cell wall structures and antioxidant response, which points to the mycotoxins overproduction as a defence mechanism. The biocontrol agent CIMO-BCA1 acts similar to tebuconazole. The results revealed different responses on the mould's metabolism when co-cultured with the two B. amyloliquefaciens, showing different modes of action of each bacterium, which opens the possibility of combining both biocontrol strategies. CONCLUSION: These results unveil different modes of action of the treatments that could help to reduce the use of toxic chemicals to combat plant pathogens worldwide. © 2023 Society of Chemical Industry.

Are women breaking the glass ceiling? A gendered analysis of the duration of sick leave in Spain.

We study the gender gap in the duration of sick leave in Spain by splitting this duration into two types of days - those which are related to biological characteristics and those derived from behavioral reasons. Using the Statistics of Accidents at Work for 2011-2019, we found that women presented longer standard durations (i.e., purely attached to physiological reasons) compared to men. However, when estimating individuals' efficiency as the ratio between actual and standard durations, we found that women were more inefficient at lower levels of income, whereas in case of men, this occurred at higher levels of income. These results were reinforced when considering that men and women do not recover from the same injury at the same rate. Women were more efficient than men across all the compensation distribution, especially at higher income levels.

Variations in Fruit Ploidy Level and Cell Size between Small- and Large-Fruited Olive Cultivars during Fruit Ontogeny.

Olive (Olea europaea L.) is one of the major oil fruit tree crops worldwide. However, the mechanisms underlying olive fruit growth remain poorly understood. Here, we examine questions regarding the interaction of endoreduplication, cell division, and cell expansion with olive fruit growth in relation to the final fruit size by measuring fruit diameter, pericarp thickness, cell area, and ploidy level during fruit ontogeny in three olive cultivars with different fruit sizes. The results demonstrate that differences in the fruit size are related to the maximum growth rate between olive cultivars during early fruit growth, about 50 days post-anthesis (DPA). Differences in fruit weight between olive cultivars were found from 35 DPA, while the distinctive fruit shape became detectable from 21 DPA, even though the increase in pericarp thickness became detectable from 7 DPA in the three cultivars. During early fruit growth, intense mitotic activity appeared during the first 21 DPA in the fruit, whereas the highest cell expansion rates occurred from 28 to 42 DPA during this phase, suggesting that olive fruit cell number is determined from 28 DPA in the three cultivars. Moreover, olive fruit of the large-fruited cultivars was enlarged due to relatively higher cell division and expansion rates compared with the small-fruited cultivar. The ploidy level of olive fruit pericarp between early and late growth was different, but similar among olive cultivars, revealing that ploidy levels are not associated with cell size, in terms of different 8C levels during olive fruit growth. In the three olive cultivars, the maximum endoreduplication level (8C) occurred just before strong cell expansion during early fruit growth in fruit pericarp, whereas the cell expansion during late fruit growth occurred without preceding endoreduplication. We conclude that the basis for fruit size differences between olive cultivars is determined mainly by different cell division and expansion rates during the early fruit growth phase. These data provide new findings on the contribution of fruit ploidy and cell size to fruit size in olive and ultimately on the control of olive fruit development.

Next generation sequencing technologies to address aberrant mRNA translation in cancer.

In this review, we explore the transformative impact of next generation sequencing technologies in the realm of translatomics (the study of how translational machinery acts on a genome-wide scale). Despite the expectation of a direct correlation between mRNA and protein content, the complex regulatory mechanisms that affect this relationship remark the limitations of standard RNA-seq approaches. Then, the review characterizes crucial techniques such as polysome profiling, ribo-seq, trap-seq, proximity-specific ribosome profiling, rnc-seq, tcp-seq, qti-seq and scRibo-seq. All these methods are summarized within the context of cancer research, shedding light on their applications in deciphering aberrant translation in cancer cells. In addition, we encompass databases and bioinformatic tools essential for researchers that want to address translatome analysis in the context of cancer biology.

Early Atf4 activity drives airway club and goblet cell differentiation.

Activating transcription factor 4 (Atf4), which is modulated by the protein kinase RNA-like ER kinase (PERK), is a stress-induced transcription factor responsible for controlling the expression of a wide range of adaptive genes, enabling cells to withstand stressful conditions. However, the impact of the Atf4 signaling pathway on airway regeneration remains poorly understood. In this study, we used mouse airway epithelial cell culture models to investigate the role of PERK/Atf4 in respiratory tract differentiation. Through pharmacological inhibition and silencing of ATF4, we uncovered the crucial involvement of PERK/Atf4 in the differentiation of basal stem cells, leading to a reduction in the number of secretory cells. ChIP-seq analysis revealed direct binding of ATF4 to regulatory elements of genes associated with osteoblast differentiation and secretory cell function. Our findings provide valuable insights into the role of ATF4 in airway epithelial differentiation and its potential involvement in innate immune responses and cellular adaptation to stress.

Real-World Evidence of Off-Label Use of Commercially Automated Insulin Delivery Systems Compared to Multiple Daily Insulin Injections in Pregnancies Complicated by Type 1 Diabetes.

Aims: To compare glycemic control and maternal-fetal outcomes of women with type 1 diabetes (T1D) using hybrid closed loop (HCL) versus multiple daily insulin injections (MDI) plus continuous glucose monitoring. Methods: Multicenter prospective cohort study of pregnant women with T1D in Spain. We evaluated HbA1c and time spent within (TIR), below (TBR), and above (TAR) the pregnancy-specific glucose range of 3.5-7.8 mmol/L. Adjusted models were performed for adverse pregnancy outcomes, including baseline maternal characteristics and center. Results: One hundred twelve women were included (HCL n = 59). Women in the HCL group had a longer duration of diabetes and higher rates of prepregnancy care. There was no between-group difference in HbA1c in any trimester. However, in the second trimester, MDI users had a greater decrease in HbA1c (-6.12 ± 9.06 vs. -2.16 ± 7.42 mmol/mol, P = 0.031). No difference in TIR (3.5-7.8 mmol/L) and TAR was observed between HCL and MDI users, but with a higher total insulin dose in the second trimester [+0.13 IU/kg·day)]. HCL therapy was associated with increased maternal weight gain during pregnancy (ßadjusted = 3.20 kg, 95% confidence interval [CI] 0.90-5.50). Regarding neonatal outcomes, newborns of HCL users were more likely to have higher birthweight (ßadjusted = 279.0 g, 95% CI 39.5-518.5) and macrosomia (ORadjusted = 3.18, 95% CI 1.05-9.67) compared to MDI users. These associations disappeared when maternal weight gain or third trimester HbA1c was included in the models. Conclusions: In a real-world setting, HCL users gained more weight during pregnancy and had larger newborns than MDI users, while achieving similar glycemic control in terms of HbA1c and TIR.

The scaffolding function of LSD1 controls DNA methylation in mouse ESCs.

Lysine-specific histone demethylase 1 (LSD1), which demethylates mono- or di- methylated histone H3 on lysine 4 (H3K4me1/2), is essential for early embryogenesis and development. Here we show that LSD1 is dispensable for mouse embryonic stem cell (ESC) self-renewal but is required for mouse ESC growth and differentiation. Reintroduction of a catalytically-impaired LSD1 (LSD1MUT) recovers the proliferation capability of mouse ESCs, yet the enzymatic activity of LSD1 is essential to ensure proper differentiation. Indeed, increased H3K4me1 in Lsd1 knockout (KO) mouse ESCs does not lead to major changes in global gene expression programs related to stemness. However, ablation of LSD1 but not LSD1MUT results in decreased DNMT1 and UHRF1 proteins coupled to global hypomethylation. We show that both LSD1 and LSD1MUT control protein stability of UHRF1 and DNMT1 through interaction with HDAC1 and the ubiquitin-specific peptidase 7 (USP7), consequently, facilitating the deacetylation and deubiquitination of DNMT1 and UHRF1. Our studies elucidate a mechanism by which LSD1 controls DNA methylation in mouse ESCs, independently of its lysine demethylase activity.

A Multicenter Prospective Evaluation of the Benefits of Two Advanced Hybrid Closed-Loop Systems in Glucose Control and Patient-Reported Outcomes in a Real-world Setting.

OBJECTIVE: Advanced hybrid closed-loop systems (AHCL) have been shown to improve glycemic control and patient-reported outcomes in type 1 diabetes. The aim was to analyze the outcomes of two commercially available AHCL in real life. RESEARCH DESIGN AND METHODS: A prospective study was performed, including adolescents and adults with type 1 diabetes, AHCL naïve, from 14 centers, who initiated the use of MM780G with SmartGuard or Tandem t:slimX2 with Control-IQ. Baseline and 3-month evaluations were performed, assessing HbA1c, time in different glycemic ranges, and patient-reported outcomes. The primary outcome was the between-group time in range 70-180 mg/dL difference from beginning to end of follow-up. RESULTS: One hundred fifty participants were included, with 75 initiating each system (age: 39.9 ± 11.4 years [16-72]; 64% female; diabetes duration: 21.6 ± 11.9 years). Time in range increased from 61.53 ± 14.01% to 76.17 ± 9.48% (P < 0.001), with no between-group differences (P = 0.591). HbA1c decreased by 0.56% (95% CI 0.44%, 0.68%) (6 mmol/mol, 95% CI 5, 7) (P < 0.001), from 7.43 ± 1.07% to 6.88 ± 0.60% (58 ± 12 to 52 ± 7 mmol/mol) in the MM780G group, and from 7.14 ± 0.70% to 6.56 ± 0.53% (55 ± 8 to 48 ± 6 mmol/mol) in the Control-IQ group (both P < 0.001 to baseline, P = 0.819 between groups). No superiority of one AHCL over the other regarding fear of hypoglycemia or quality of life was found. Improvement in diabetes-related distress was higher in Control-IQ users (P = 0.012). Sleep quality was improved (PSQI: from 6.94 ± 4.06 to 6.06 ± 4.05, P = 0.004), without differences between systems. Experience with AHCL, evaluated by the INSPIRE measures, exceeded the expectations. CONCLUSIONS: The two AHCL provide significant improvement in glucose control and satisfaction, with no superiority of one AHCL over the other.