Capturing totipotency in human cells through spliceosomal repression.

The cleavage of zygotes generates totipotent blastomeres. In human 8-cell blastomeres, zygotic genome activation (ZGA) occurs to initiate the ontogenesis program. However, capturing and maintaining totipotency in human cells pose significant challenges. Here, we realize culturing human totipotent blastomere-like cells (hTBLCs). We find that splicing inhibition can transiently reprogram human pluripotent stem cells into ZGA-like cells (ZLCs), which subsequently transition into stable hTBLCs after long-term passaging. Distinct from reported 8-cell-like cells (8CLCs), both ZLCs and hTBLCs widely silence pluripotent genes. Interestingly, ZLCs activate a particular group of ZGA-specific genes, and hTBLCs are enriched with pre-ZGA-specific genes. During spontaneous differentiation, hTBLCs re-enter the intermediate ZLC stage and further generate epiblast (EPI)-, primitive endoderm (PrE)-, and trophectoderm (TE)-like lineages, effectively recapitulating human pre-implantation development. Possessing both embryonic and extraembryonic developmental potency, hTBLCs can autonomously generate blastocyst-like structures in vitro without external cell signaling. In summary, our study provides key criteria and insights into human cell totipotency.

Mouse totipotent stem cells captured and maintained through spliceosomal repression.

Since establishment of the first embryonic stem cells (ESCs), in vitro culture of totipotent cells functionally and molecularly comparable with in vivo blastomeres with embryonic and extraembryonic developmental potential has been a challenge. Here we report that spliceosomal repression in mouse ESCs drives a pluripotent-to-totipotent state transition. Using the splicing inhibitor pladienolide B, we achieve stable in vitro culture of totipotent ESCs comparable at molecular levels with 2- and 4-cell blastomeres, which we call totipotent blastomere-like cells (TBLCs). Mouse chimeric assays combined with single-cell RNA sequencing (scRNA-seq) demonstrate that TBLCs have a robust bidirectional developmental capability to generate multiple embryonic and extraembryonic cell lineages. Mechanically, spliceosomal repression causes widespread splicing inhibition of pluripotent genes, whereas totipotent genes, which contain few short introns, are efficiently spliced and transcriptionally activated. Our study provides a means for capturing and maintaining totipotent stem cells.

A transient transcriptional activation governs unpolarized-to-polarized morphogenesis during embryo implantation.

During implantation, embryos undergo an unpolarized-to-polarized transition to initiate postimplantation morphogenesis. However, the underlying molecular mechanism is unknown. Here, we identify a transient transcriptional activation governing embryonic morphogenesis and pluripotency transition during implantation. In naive pluripotent embryonic stem cells (ESCs), which represent preimplantation embryos, we find that the microprocessor component DGCR8 can recognize stem-loop structures within nascent mRNAs to sequester transcriptional coactivator FLII to suppress transcription directly. When mESCs exit from naive pluripotency, the ERK/RSK/P70S6K pathway rapidly activates, leading to FLII phosphorylation and disruption of DGCR8/FLII interaction. Phosphorylated FLII can bind to transcription factor JUN, activating cell migration-related genes to establish poised pluripotency akin to implanting embryos. Resequestration of FLII by DGCR8 drives poised ESCs into formative pluripotency. In summary, we identify a DGCR8/FLII/JUN-mediated transient transcriptional activation mechanism. Disruption of this mechanism inhibits naive-poised-formative pluripotency transition and the corresponding unpolarized-to-polarized transition during embryo implantation, which are conserved in mice and humans.

Imaging tunable Luttinger liquid systems in van der Waals heterostructures.

One-dimensional (1D) interacting electrons are often described as a Luttinger liquid1-4 having properties that are intrinsically different from those of Fermi liquids in higher dimensions5,6. In materials systems, 1D electrons exhibit exotic quantum phenomena that can be tuned by both intra- and inter-1D-chain electronic interactions, but their experimental characterization can be challenging. Here we demonstrate that layer-stacking domain walls (DWs) in van der Waals heterostructures form a broadly tunable Luttinger liquid system, including both isolated and coupled arrays. We have imaged the evolution of DW Luttinger liquids under different interaction regimes tuned by electron density using scanning tunnelling microscopy. Single DWs at low carrier density are highly susceptible to Wigner crystallization consistent with a spin-incoherent Luttinger liquid, whereas at intermediate densities dimerized Wigner crystals form because of an enhanced magneto-elastic coupling. Periodic arrays of DWs exhibit an interplay between intra- and inter-chain interactions that gives rise to new quantum phases. At low electron densities, inter-chain interactions are dominant and induce a 2D electron crystal composed of phased-locked 1D Wigner crystal in a staggered configuration. Increased electron density causes intra-chain fluctuation potentials to dominate, leading to an electronic smectic liquid crystal phase in which electrons are ordered with algebraical correlation decay along the chain direction but disordered between chains. Our work shows that layer-stacking DWs in 2D heterostructures provides opportunities to explore Luttinger liquid physics.

Near-Barrierless CO Oxidation Using Phosphotungstic Acid-Supported Single-Atom Catalysts.

Efficient CO oxidation at ambient or low temperatures is essential for environmental purification and selective CO oxidation in H2, yet achieving this remains a challenge with current methodologies. In this research, we extensively evaluated the catalytic performance of phosphotungstic acid (PTA)-supported 11 M1/PTA single-atom catalysts (SACs) using density functional theory calculations across both gas phase and 12 common solvents. The Rh1/PTA, Pd1/PTA, and Pt1/PTA systems exhibit moderate CO adsorption energies, facilitating the feasibility of oxygen vacancy formation. Remarkably, the Pd1/PTA and Pt1/PTA catalysts exhibited negligible energy barriers and demonstrated exceptionally high catalytic rates, with values reaching up to (1 × 1010)11, markedly exceeding the threshold for room temperature reactions, set at 6.55 × 108. This phenomenon is attributed to a transition from the high-energy barrier processes of oxygen dissociation in O2 and N-O bond dissociation in N2O to the more efficient dissociation of H2O2. Orbital analysis and charge variations at metal sites throughout the reaction process provide deeper insights into the role of the three metal catalytic sites in CO activation. Our findings not only reveal key aspects of SACs in facilitating CO oxidation at low temperatures but also provide valuable insights for future catalytic reaction mechanism studies and environmental applications.

Surface Reconstruction for Selective Oxidation of Tetrahydroisoquinoline.

Integration of hydrogen evolution with the oxidation of organic substances in one electrochemical system is highly desirable. However, achieving selective oxidation of organic substances in the integrated system is still highly challenging. In this study, a phosphorylated NiMoO4 nanoneedle-like array was designed as the catalytic active electrode for the integration of highly selective electrochemical dehydrogenation of tetrahydroisoquinolines (THIQs) with hydrogen production. The leaching of anions, including MoO42- and PO43-, facilitates the reconstruction of the catalyst. As a result, nickel oxyhydroxides with the doping of PO43- and richness of defects are in situ formed. In situ Raman and density functional theory calculations have shown that the high catalytic activity is attributed to the in situ formed PO43- involved NiOOH substance. In the dehydrogenation process, the involved C-H bond but not the N-H bond is first destroyed. A two-electrode system was then fabricated with the optimized electrode that shows a benchmark current density of 10 mA cm-2 at 1.783 V, providing a yield of 70% for dihydroisoquinolines. A robust stability was also shown for this integrated electrochemical system. The understanding of the reconstruction behavior and the achievement of selective dehydrogenation will provide some hints for electrochemical synthesis.

Consumer brand and category switching behaviors after food safety incidents: Factors and mechanisms.

The excessive mold found in Three Squirrels' nuts and the clenbuterol abuse of Shuanghui are two infamous food safety incidents in China. We adopted push-pull-mooring theory to conduct a model and examined the factors influencing consumer short-term or long-term brand-switching or category-switching behaviors following the two food safety incidents. We employed multinomial logistic regression and structural equation modeling as tools to analyze 1027 valid questionnaires. The results, for the first time, revealed that perceived risk, alternative selectivity, alternative attractiveness, controllability attribution, and habits were key push, pull and mooring factors influencing Chinese consumers' brand and category switching from food brands under food safety crisis, and most importantly, that their influential paths differed greatly under the two food safety incidents, suggesting a different influential mechanism across two product categories (i.e., utilitarian food and hedonic food). These findings throw light on the predictors and mechanisms that affect consumer brand and category switching from food brands under food safety crisis and help associated food businesses develop more targeted and powerful crisis management and public relations strategies.

An artificial intelligence model based on transrectal ultrasound images of biopsy needle tract tissues to differentiate prostate cancer.

PURPOSE: We aimed to develop an artificial intelligence (AI) model based on transrectal ultrasonography (TRUS) images of biopsy needle tract (BNT) tissues for predicting prostate cancer (PCa) and to compare the PCa diagnostic performance of the radiologist model and clinical model. METHODS: A total of 1696 2D prostate TRUS images were involved from 142 patients between July 2021 and May 2022. The ResNet50 network model was utilized to train classification models with different input methods: original image (Whole model), BNT (Needle model), and combined image [Feature Pyramid Networks (FPN) model]. The training set, validation set, and test set were randomly assigned, then randomized 5-fold cross-validation between the training set and validation set was performed. The diagnostic effectiveness of AI models and image combination was accessed by an independent testing set. Then, the optimal AI model and image combination were selected to compare the diagnostic efficacy with that of senior radiologists and the clinical model. RESULTS: In the test set, the area under the curve, specificity, and sensitivity of the FPN model were 0.934, 0.966, and 0.829, respectively; the diagnostic efficacy was improved compared with the Whole and Needle models, with statistically significant differences (P < 0.05), and was better than that of senior radiologists (area under the curve: 0.667). The FPN model detected more PCa compared with senior physicians (82.9% vs. 55.8%), with a 61.3% decrease in the false-positive rate and a 23.2% increase in overall accuracy (0.887 vs. 0.655). CONCLUSION: The proposed FPN model can offer a new method for prostate tissue classification, improve the diagnostic performance, and may be a helpful tool to guide prostate biopsy.

Understanding Heterogeneity in Individual Responses to Digital Lifestyle Intervention Through Self-Monitoring Adherence Trajectories in Adults With Overweight or Obesity: Secondary Analysis of a 6-Month Randomized Controlled Trial.

BACKGROUND: Achieving clinically significant weight loss through lifestyle interventions for obesity management is challenging for most individuals. Improving intervention effectiveness involves early identification of intervention nonresponders and providing them with timely, tailored interventions. Early and frequent self-monitoring (SM) adherence predicts later weight loss success, making it a potential indicator for identifying nonresponders in the initial phase. OBJECTIVE: This study aims to identify clinically meaningful participant subgroups based on longitudinal adherence to SM of diet, activity, and weight over 6 months as well as psychological predictors of participant subgroups from a self-determination theory (SDT) perspective. METHODS: This was a secondary data analysis of a 6-month digital lifestyle intervention for adults with overweight or obesity. The participants were instructed to perform daily SM on 3 targets: diet, activity, and weight. Data from 50 participants (mean age: 53.0, SD 12.6 y) were analyzed. Group-based multitrajectory modeling was performed to identify subgroups with distinct trajectories of SM adherence across the 3 SM targets. Differences between subgroups were examined for changes in clinical outcomes (ie, body weight, hemoglobin A1c) and SDT constructs (ie, eating-related autonomous motivation and perceived competence for diet) over 6 months using linear mixed models. RESULTS: Two distinct SM trajectory subgroups emerged: the Lower SM group (21/50, 42%), characterized by all-around low and rapidly declining SM, and the Higher SM group (29/50, 58%), characterized by moderate and declining diet and weight SM with high activity SM. Since week 2, participants in the Lower SM group exhibited significantly lower levels of diet (P=.003), activity (P=.002), and weight SM (P=.02) compared with the Higher SM group. In terms of clinical outcomes, the Higher SM group achieved a significant reduction in body weight (estimate: -6.06, SD 0.87 kg; P<.001) and hemoglobin A1c (estimate: -0.38, SD 0.11%; P=.02), whereas the Lower SM group exhibited no improvements. For SDT constructs, both groups maintained high levels of autonomous motivation for over 6 months. However, the Lower SM group experienced a significant decline in perceived competence (P=.005) compared with the Higher SM group, which maintained a high level of perceived competence throughout the intervention (P=.09). CONCLUSIONS: The presence of the Lower SM group highlights the value of using longitudinal SM adherence trajectories as an intervention response indicator. Future adaptive trials should identify nonresponders within the initial 2 weeks based on their SM adherence and integrate intervention strategies to enhance perceived competence in diet to benefit nonresponders. TRIAL REGISTRATION: ClinicalTrials.gov NCT05071287; https://clinicaltrials.gov/study/NCT05071287. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1016/j.cct.2022.106845.

Using a smartphone-based self-management platform to study sex differences in Parkinson's disease: multicenter, cross-sectional pilot study.

BACKGROUND: Patient-reported outcome (PRO) is a distinct and indispensable dimension of clinical characteristics and recent advances have made remote PRO measurement possible. Sex difference in PRO of Parkinson's disease (PD) is hardly extensively researched. METHODS: A smartphone-based self-management platform, offering remote PRO measurement for PD patients, has been developed. A total of 1828 PD patients, including 1001 male patients and 827 female patients, were enrolled and completed their PRO submission through this platform. RESULTS: Sex differences in PROs have been identified. The female group had a significantly lower height, weight, and body mass index (BMI) than the male group (P < 0.001). For motor symptoms, a higher proportion of patients reporting dyskinesia was observed in the female group. For non-motor symptoms, there is a higher percentage (P < 0.001) as well as severity (P = 0.016) of depression in the female group. More male patients reported hyposmia, lisp, drooling, dysuria, frequent urination, hypersexuality, impotence, daytime sleepiness, and apathy than females (P < 0.05). In contrast, more female patients reported headache, palpation, body pain, anorexia, nausea, urinal incontinence, anxiety, insomnia (P < 0.05) than males. CONCLUSIONS: We provide evidence for sex differences in PD through the data collected from our platform. These results highlighted the importance of gender in clinical decision-making, and also support the feasibility of remote PRO measurement through a smartphone-based self-management platform in patients with PD.

Nomogram to predict radicular grooves in maxillary lateral incisors in preoperative orthodontic population.

OBJECTIVES: This study aimed to develop and validate a predictive nomogram for diagnosing radicular grooves (RG) in maxillary lateral incisors (MLIs), integrating demographic information, anatomical measurements, and Cone Beam Computed Tomography (CBCT) data to diagnose the RG in MLIs based on the clinical observation before resorting to the CBCT scan. MATERIALS AND METHODS: A retrospective cohort of orthodontic patients from the School and Hospital of Stomatology, Wuhan University, was analyzed, including demographic characteristics, photographic anatomical assessments, and CBCT diagnoses. The cohort was divided into development and validation groups. Univariate and multivariate logistic regression analyses identified significant predictors of RG, which informed the development of a nomogram. This nomogram's performance was validated using receiver operating characteristic analysis. RESULTS: The study included 381 patients (64.3% female) and evaluated 760 MLIs, with RG present in 26.25% of MLIs. The nomogram incorporated four significant anatomical predictors of RG presence, demonstrating substantial predictive efficacy with an area under the curve of 0.75 in the development cohort and 0.71 in the validation cohort. CONCLUSIONS: A nomogram for the diagnosis of RG in MLIs was successfully developed. This tool offers a practical checklist of anatomical predictors to improve the diagnostic process in clinical practice. CLINICAL RELEVANCE: The developed nomogram provides a novel, evidence-based tool to enhance the detection and treatment planning of MLIs with RG in diagnostic and therapeutic strategies.

Water retention property and microscopic mechanism of shallow soil in inner dump improved by fly ash and polyacrylamide.

Improving the water retention property of shallow soil in the inner dump is the key step in the sustainable development of mines. In recent years, the use of fly ash to improve the structure of the inner dump and polyacrylamide as an additive to enhance water retention was an effective method. The article used a physical model test, filter paper method, and microstructure analysis method to compare and analyze the water retention property and microstructure of slope-improved soil with different fly ash and polyacrylamide content. The results show that the combined use of fly ash and polyacrylamide improved the water retention property of the amended soil. Fly ash and polyacrylamide had a greater effect on the low suction stage of the amended soil. Polyacrylamide reacted with water and bound soil particles to form aggregates, and the structural unit bodies were a block structure. Fly ash was non-sticky and was a matrix of fine particles, which weakened the bonding effect of polyacrylamide, and reduced the aggregates of soil particles, and the structural unit bodies were a flocculated structure of aggregates mixed with matrix. This, in turn, enhanced the capillary action and improved the water retention performance of the improved soil. In addition, polyacrylamide could connect water molecules, further enhancing the water retention property of the improved soil. The combined use of fly ash and polyacrylamide improved the available water content of improved soil, providing a viable and sustainable solution for improving the comprehensive utilization of fly ash, and laid the foundation for land reclamation at the inner dump.

Involvement of lysyl oxidase in the pathogenesis of arterial stiffness in chronic kidney disease.

Patients with chronic kidney disease (CKD) are at increased risk for adverse cardiovascular events. CKD is associated with increases in arterial stiffness, whereas improvements in arterial stiffness correlate with better survival. However, arterial stiffness is increased early in CKD, suggesting that there might be additional factors, unique to kidney disease, that increase arterial stiffness. Lysyl oxidase (LOX) is a key mediator of collagen cross linking and matrix remodeling. LOX is predominantly expressed in the cardiovascular system, and its upregulation has been associated with increased tissue stiffening and extracellular matrix remodeling. Thus, this study was designed to evaluate the role of increased LOX activity in inducing aortic stiffness in CKD and whether ß-aminopropionitrile (BAPN), a LOX inhibitor, could prevent aortic stiffness by reducing collagen cross linking. Eight-week-old male C57BL/6 mice were subjected to 5/6 nephrectomy (Nx) or sham surgery. Two weeks after surgery, mice were randomized to BAPN (300 mg/kg/day in water) or vehicle treatment for 4 wk. Aortic stiffness was assessed by pulse wave velocity (PWV) using Doppler ultrasound. Aortic levels of LOX were assessed by ELISA, and cross-linked total collagen levels were analyzed by mass spectrometry and Sircol assay. Nx mice showed increased PWV and aortic wall remodeling compared with control mice. Collagen cross linking was increased in parallel with the increases in total collagen in the aorta of Nx mice. In contrast, Nx mice that received BAPN treatment showed decreased cross-linked collagens and PWV compared with that received vehicle treatment. Our results indicated that LOX might be an early and key mediator of aortic stiffness in CKD.NEW & NOTEWORTHY Arterial stiffness in CKD is associated with adverse cardiovascular outcomes. However, the mechanisms underlying increased aortic stiffness in CKD are unclear. Herein, we demonstrated that 1) increased aortic stiffness in CKD is independent of hypertension and calcification and 2) LOX-mediated changes in extracellular matrix are at least in part responsible for increased aortic stiffness in CKD. Prevention of excess LOX may have therapeutic potential in alleviating increased aortic stiffness and improving cardiovascular disease in CKD.

Activatable Lanthanide Nanoprobes with Dye-Sensitized Second Near-Infrared Luminescence for in Vivo Inflammation Imaging.

Lanthanide nanoparticles exhibit unique photophysical properties and thus emerge as promising second near-infrared (NIR-II) optical agents. However, the limited luminescence brightness hampers their construction of activatable NIR-II probes. Herein, we report the synthesis of dye-sensitized lanthanide nanoprobes (NaGdF4:Nd/ICG; indocyanine green (ICG)) and their further development for in vivo activatable imaging of hypochlorite (ClO-). Dye sensitization using ICG not only shifts the optimal doping concentration of Nd3+ from 5 to 20 mol % but also leads to a 5-fold NIR-II enhancement relative to the ICG-free counterpart. Mechanistic studies reveal that such a luminescence enhancement of NaGdF4:Nd at high Nd3+ concentration is ascribed to an alleviated cross-relaxation effect due to the broad absorption of ICG and faster energy transfer process. Taking advantage of dye oxidation, the nanoprobes enable activatable NIR-II imaging of hypochlorous acid (ClO-) in a drug-induced lymphatic inflammation mouse model. This work thus provides a simple, yet effective luminescence enhancement strategy for constructing lanthanide nanoprobes at higher activator doping concentration toward activatable NIR-II molecular imaging.

Comparative Performance of Endoscopic Ultrasound-Based Techniques in Patients With Pancreatic Cystic Lesions: A Network Meta-Analysis.

INTRODUCTION: Evidence on the comparative diagnostic performance of endoscopic ultrasound (EUS)-based techniques for pancreatic cystic lesions (PCLs) is limited. This network meta-analysis comprehensively compared EUS-based techniques for PCL diagnosis. METHODS: A comprehensive literature search was performed for all comparative studies assessing the accuracy of 2 or more modalities for PCL diagnosis. The primary outcome was the diagnostic efficacy for mucinous PCLs. Secondary outcomes were the diagnostic efficacy for malignant PCLs, diagnostic success rate, and adverse event rate. A network meta-analysis was conducted using the ANOVA model to assess the diagnostic accuracy of each index. RESULTS: Forty studies comprising 3,641 patients were identified. The network ranking of the superiority index for EUS-guided needle-based confocal laser endomicroscopy (EUS-nCLE) and EUS-guided through-the-needle biopsy (EUS-TTNB) were significantly higher than other techniques for differentiating mucinous PCLs; besides, EUS-TTNB was also the optimal technique in identifying malignant PCLs. The evidence was inadequate for EUS-nCLE diagnosing malignant PCLs and contrast-enhanced harmonic EUS diagnosing both mucinous and malignant PCLs. Glucose showed a high sensitivity but low specificity, and molecular analysis (KRAS, GNAS, and KRAS + GNAS mutations) showed a high specificity but low sensitivity for diagnosing mucinous PCLs. Satisfactory results were not obtained during the evaluation of the efficiency of pancreatic cyst fluid (PCF) biomarkers in detecting malignant PCLs. DISCUSSION: For centers with relevant expertise and facilities, EUS-TTNB and EUS-nCLE were better choices for the diagnosis of PCLs. Further studies are urgently required for further improving PCF biomarkers and validating the diagnostic performance of the index techniques.

All fiber optic current sensor based on phase-shift fiber loop ringdown structure.

An all fiber optic current sensor (AFOCS) utilizing ordinary optical fiber is proposed and demonstrated, which is implemented with a phase-shift fiber loop ringdown (PS-FLRD) structure. The current-induced rotation angle is converted into a minute change in transmittance of the fiber loop, which can be obtained by measuring the phase shift. The current sensitivity is improved by allowing optical signals to traverse the sensing fiber repeatedly. The relationship between the current sensitivity, intrinsic phase shift, and initial transmittance of the fiber loop is numerically analyzed, and the tunable sensitivity is experimentally verified by adjusting the modulation frequency. An optimal current sensitivity of 0.8158°/A is experimentally obtained for the proposed sensor, and the minimum detectable current is at least 100 mA. The proposed sensor requires fewer polarization elements compared with the common type of fiber optic current sensor (FOCS) and has the characteristics of simple structure, high sensitivity, and ease of operation; it will be a promising approach in practical applications.

In Vivo 18 F-Florzolotau Tau Positron Emission Tomography Imaging in Parkinson's Disease Dementia.

BACKGROUND: Tau pathology is observed during autopsy in many patients with Parkinson's disease dementia (PDD). Positron emission tomography (PET) imaging using the tracer 18 F-florzolotau has the potential to capture tau accumulation in the living brain. OBJECTIVE: The aim was to describe the results of 18 F-florzolotau PET/CT (computed tomography) imaging in patients with PDD. METHODS: Ten patients with PDD, 9 with Parkinson's disease with normal cognition (PD-NC), and 9 age-matched healthy controls (HCs) were enrolled. Clinical assessments and 18 F-florzolotau PET/CT imaging were performed. RESULTS: 18 F-Florzolotau uptake was significantly higher in the cortical regions of patients with PDD compared with both PD-NC and HCs, especially in the temporal lobe. Notably, 18 F-florzolotau uptake in the occipital lobe of patients with PDD showed a significant correlation with cognitive impairment as reflected by Mini-Mental State Examination (MMSE) scores. CONCLUSIONS: 18 F-Florzolotau PET imaging can effectively capture the occurrence of tau pathology in patients with PDD, which was also linked to MMSE scores. © 2022 International Parkinson and Movement Disorder Society.

PECAM-1 drives ß-catenin-mediated EndMT via internalization in colon cancer with diabetes mellitus.

BACKGROUND: Diabetes mellitus (DM) is considered to be a risk factor in carcinogenesis and progression, although the biological mechanisms are not well understood. Here we demonstrate that platelet-endothelial cell adhesion molecule 1 (PECAM-1) internalization drives ß-catenin-mediated endothelial-mesenchymal transition (EndMT) to link DM to cancer. METHODS: The tumor microenvironment (TME) was investigated for differences between colon cancer with and without DM by mRNA-microarray analysis. The effect of DM on colon cancer was determined in clinical patients and animal models. Furthermore, EndMT, PECAM-1 and Akt/GSK-3ß/ß-catenin signaling were analyzed under high glucose (HG) and human colon cancer cell (HCCC) supernatant (SN) or coculture conditions by western and immunofluorescence tests. RESULTS: DM promoted the progression and EndMT occurrence of colon cancer (CC). Regarding the mechanism, DM induced PECAM-1 defection from the cytomembrane, internalization and subsequent accumulation around the cell nucleus in endothelial cells, which promoted ß-catenin entry into the nucleus, leading to EndMT occurrence in CC with DM. Additionally, Akt/GSK-3ß signaling was enhanced to inhibit the degradation of ß-catenin, which regulates the process of EndMT. CONCLUSIONS: PECAM-1 defects and/or internalization are key events for ß-catenin-mediated EndMT, which is significantly boosted by enhanced Akt/GSK-3ß signaling in the DM-associated TME. This contributes to the mechanism by which DM promotes the carcinogenesis and progression of CC. Video Abstract.

Impact of ¡Míranos! on parent-reported home-based healthy energy balance-related behaviors in low-income Latino preschool children: a clustered randomized controlled trial.

BACKGROUND: Widespread establishment of home-based healthy energy balance-related behaviors (EBRBs), like diet, physical activity, sedentary behavior, screen time, and sleep, among low-income preschool-aged children could curb the childhood obesity epidemic. We examined the effect of an 8-month multicomponent intervention on changes in EBRBs among preschool children enrolled in 12 Head Start centers. METHODS: The Head Start (HS) centers were randomly assigned to one of three treatment arms: center-based intervention group (CBI), center-based plus home-based intervention group (CBI + HBI), or control. Before and following the intervention, parents of 3-year-olds enrolled in participating HS centers completed questionnaires about their child's at-home EBRBs. Adult-facilitated physical activity (PA) was measured by an index based on questions assessing the child's level of PA participation at home, with or facilitated by an adult. Fruit, vegetable, and added sugar intake were measured via a short food frequency questionnaire, and sleep time and screen time were measured using 7-day logs. A linear mixed effects model examined the intervention's effect on post-intervention changes in PA, intake of fruit, vegetable, and added sugar, sleep time, and screen time from baseline to post-intervention. RESULTS: A total of 325 parents participated in the study (CBI n = 101; CBI + HBI n = 101; and control n = 123). Compared to control children, CBI and CBI + HBI parents reported decreases in children's intake of added sugar from sugar-sweetened beverages. Both CBI and CBI + HBI parents also reported smaller increases in children's average weekday screen time relative to controls. In addition, CBI + HBI parents reported CBI + HBI parents reported increases in children's adult-facilitated PA, fruit and vegetable intake, and daily sleep time during weekdays (excluding weekends) and the total week from baseline to post-intervention, while children in the CBI increased sleep time over the total week compared to the children in the control group. CONCLUSIONS: Parent engagement strengthened the improvement in parent-reported EBRBs at home in young children participating in an evidence-based obesity prevention program in a childcare setting. Future studies should investigate equity-related contextual factors that influence the impact of obesity prevention in health-disparity populations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03590834. Registered July 18, 2018, https://clinicaltrials.gov/ct2/show/NCT03590834.

Selective Defluoroalkylation and Hydrodefluorination of Trifluoromethyl Groups Photocatalyzed by Dihydroacridine Derivatives.

The selective functionalization of trifluoromethyl groups through C-F cleavage poses a significant challenge due to the high bond energy of the C(sp3)-F bonds. Herein, we present dihydroacridine derivatives as photocatalysts that can functionalize the C-F bond of trifluoromethyl groups with various alkenes under mild conditions. Mechanistic studies and DFT calculations revealed that upon irradiation, the dihydroacridine derivatives exhibit high reducibility and function as photocatalysts for reductive defluorination. This process involves a sequential single-electron transfer mechanism. This research provides valuable insights into the properties of dihydroacridine derivatives as photocatalysts, highlighting the importance of maintaining a planar conformation and a large conjugated system for optimal catalytic activity. These findings facilitate the efficient catalytic reduction of inert chemical bonds.