Exploring Technology's Influence on Health Behaviours and Well-being in Type 1 Diabetes: a Review.

PURPOSE OF REVIEW: Maintaining positive health behaviours promotes better health outcomes for people with type 1 diabetes (T1D). However, implementing these behaviours may also lead to additional management burdens and challenges. Diabetes technologies, including continuous glucose monitoring systems, automated insulin delivery systems, and digital platforms, are being rapidly developed and widely used to reduce these burdens. Our aim was to review recent evidence to explore the influence of these technologies on health behaviours and well-being among adults with T1D and discuss future directions. RECENT FINDINGS: Current evidence, albeit limited, suggests that technologies applied in diabetes self-management education and support (DSME/S), nutrition, physical activity (PA), and psychosocial care areas improved glucose outcomes. They may also increase flexibility in insulin adjustment and eating behaviours, reduce carb counting burden, increase confidence in PA, and reduce mental burden. Technologies have the potential to promote health behaviours changes and well-being for people with T1D. More confirmative studies on their effectiveness and safety are needed to ensure optimal integration in standard care practices.

Nonadjacent Wireless Electrotherapy for Tissue Repair by a 3D-Printed Bioresorbable Fully Soft Triboelectric Nanogenerator.

Electrotherapy is a promising tissue repair technique. However, electrotherapy devices are frequently complex and must be placed adjacent to injured tissue, thereby limiting their clinical application. Here, we propose a general strategy to facilitate tissue repair by modulating endogenous electric fields with nonadjacent (approximately 44 mm) wireless electrotherapy through a 3D-printed entirely soft and bioresorbable triboelectric nanogenerator based stimulator, without any electrical accessories, which has biomimetic mechanical properties similar to those of soft tissue. In addition, the feasibility of using the stimulator to construct an electrical double layer with tissue for nonadjacent wireless electrotherapy was demonstrated by skin and muscle injury models. The treated groups showed significantly improved tissue repair compared with the control group. In conclusion, we developed a promising electrotherapy strategy and may inspire next-generation electrotherapy for tissue repair.

Cementum protein 1 gene-modified adipose-derived mesenchymal stem cell sheets enhance periodontal regeneration in osteoporosis rat.

BACKGROUND AND OBJECTIVES: Osteoporosis (OP) and periodontitis are both diseases with excessive bone resorption, and the number of patients who suffer from these diseases is expected to increase. OP has been identified as a risk factor that accelerates the pathological process of periodontitis. Achieving effective and safe periodontal regeneration in OP patients is a meaningful challenge. This study aimed to assess the efficacy and biosecurity of human cementum protein 1 (hCEMP1) gene-modified cell sheets for periodontal fenestration defect regeneration in an OP rat model. MATERIALS AND METHODS: Rat adipose-derived mesenchymal stem cells (rADSCs) were isolated from Sprague-Dawley rats. After primary culture, rADSCs were subjected to cell surface analysis and multi-differentiation assay. And rADSCs were transduced with hCEMP1 by lentiviral vector, and hCEMP1 gene-modified cell sheets were generated. The expression of hCEMP1 was evaluated by reverse transcription polymerase chain reaction and immunocytochemistry staining, and transduced cell proliferation was evaluated by Cell Counting Kit-8. The hCEMP1 gene-modified cell sheet structure was detected by histological analysis and scanning electron microscopy. Osteogenic and cementogenic-associated gene expression was evaluated by real-time quantitative polymerase chain reaction. In addition, an OP rat periodontal fenestration defect model was used to evaluate the regeneration effect of hCEMP1 gene-modified rADSC sheets. The efficacy was assessed with microcomputed tomography and histology, and the biosecurity of gene-modified cell sheets was evaluated by histological analysis of the spleen, liver, kidney and lung. RESULTS: The rADSCs showed a phenotype of mesenchymal stem cells and possessed multi-differentiation capacity. The gene and protein expression of hCEMP1 through lentiviral transduction was confirmed, and there was no significant effect on rADSC proliferation. Overexpression of hCEMP1 upregulated osteogenic and cementogenic-related genes such as runt-related transcription factor 2, bone morphogenetic protein 2, secreted phosphoprotein 1 and cementum attachment protein in the gene-modified cell sheets. The fenestration lesions in OP rats treated with hCEMP1 gene-modified cell sheets exhibited complete bone bridging, cementum and periodontal ligament formation. Furthermore, histological sections of the spleen, liver, kidney and lung showed no evident pathological damage. CONCLUSION: This pilot study demonstrates that hCEMP1 gene-modified rADSC sheets have a marked ability to enhance periodontal regeneration in OP rats. Thus, this approach may represent an effective and safe strategy for periodontal disease patients with OP.

Strophioblachins A-K, Structurally Intriguing Diterpenoids from Strophioblachia fimbricalyx with Potential Anticardiac Hypertrophic Inhibitory Activity.

Three new rearranged diterpenoids, strophioblachins A-C (1-3), eight new diterpenoids, strophioblachins D-K (4-11), and seven previously described diterpenoids (12-18) were purified from the aerial parts of Strophioblachia fimbricalyx. Compounds 1 and 2 contain a rare 6/6/5/6 ring system, while 3 has an uncommon tricyclo[4.4.0.08,9]tridecane-bridged unit, and their diterpenoid skeletons are being reported for the first time. Utilizing spectroscopic and HRESIMS data analysis, the structures of the new compounds (1-11) were established, and ECD and 13C NMR calculations were used to confirm the relative and absolute configurations of 11 and 9. The absolute configurations of compounds 1, 3, and 10 were established using single-crystal X-ray diffraction. The results of testing for anticardiac hypertrophic activity demonstrated that compounds 10 and 15 dose-dependently lowered the mRNA expression of Nppa and Nppb. Protein levels were confirmed by Western blotting, which also demonstrated that compounds 10 and 15 lowered the expression of the hypertrophic marker ANP. The cytotoxic activity against neonatal rat cardiomyocytes was assayed in vitro by the CCK-8 and ELISA methods, and the results showed that compounds 10 and 15 were only very weakly active in the range.

Managing Impending Nonsevere Hypoglycemia With Oral Carbohydrates in Type 1 Diabetes: The REVERSIBLE Trial.

OBJECTIVE: Current guidelines recommend initiating treatment for nonsevere (NS) hypoglycemia with 15 g carbohydrates (CHO) at 15-min intervals when blood glucose (BG) reaches <70 mg/dL (3.9 mmol/L). Despite this recommendation, NS hypoglycemia management remains challenging for individuals living with type 1 diabetes (T1D). We aimed to assess the efficacy of 15 g CHO at higher BG levels. RESEARCH DESIGN AND METHODS: A total of 29 individuals with T1D participated in an open-label crossover study. After an inpatient subcutaneous insulin-induced decrease in BG in the fasting state, 16 g CHO was administered orally at a plasma glucose (PG) of <70 (3.9), ≤80 (4.5), or ≤90 mg/dL (5.0 mmol/L). The primary outcome was time spent in hypoglycemia (<70 mg/dL) after initial CHO intake. RESULTS: When comparing the <70 (control) with the ≤80 and ≤90 mg/dL treatment groups, 100 vs. 86 (P = 0.1201) vs. 34% (P < 0.0001) of participants reached hypoglycemia, respectively. These hypoglycemic events lasted 26.0 ± 12.6 vs. 17.9 ± 14.7 (P = 0.026) vs. 7.1 ± 11.8 min (P = 0.002), with a PG nadir of 56.57 ± 9.91 vs. 63.60 ± 7.93 (P = 0.008) vs. 73.51 ± 9.37 mg/dL (P = 0.002), respectively. In the control group, 69% of participants required more than one treatment to reach or maintain normoglycemia (≥70 mg/dL), compared with 52% in the ≤80 mg/dL group and 31% in the ≤90 mg/dL group, with no significant rebound hyperglycemia (>180 mg/dL) within the first hour. CONCLUSIONS: For some impending NS hypoglycemia episodes, individuals with TID could benefit from CHO intake at a higher BG level.

Asiaticasics A-O, structurally intriguing coumarins from Toddalia asiatica with potential inflammatory inhibitory activity.

Ethyl acetate fraction of Toddalia asiatica was fractionated to yield fifteen previously undescribed prenylated coumarins, asiaticasics A-O (1-15) along with nine (16-24) known derivatives. The structures of these undescribed coumarins were established by spectroscopic analysis and reference data. Biological activity evaluation showed that compound 3 with the IC50 value of 2.830 µM and compound 12 with the IC50 value of 0.682 µM owned anti-inflammatory activity by detecting the rate of lactate dehydrogenase release in pyroptosis J774A.1 cells. The results showed that the expression of Caspase-1 and IL-1ß was decreased in a dose-dependent manner in the compound 12 treatment group, suggesting that compound 12 may reduce pyroptosis by inhibiting NLRP3 inflammasome. To further determine that compound 12 treatment can inhibit macrophage pyroptosis, morphological observation was performed and the results were consistent with the bioactivity evaluation.

Gelsenicine disrupted the intestinal barrier of Caenorhabditis elegans.

Gelsemium elegans Benth. (G. elegans) is a traditional medicinal herb that has anti-inflammatory, analgesic, sedative, and detumescence effects. However, it can also cause intestinal side effects such as abdominal pain and diarrhea. The toxicological mechanisms of gelsenicine are still unclear. The objective of this study was to assess enterotoxicity induced by gelsenicine in the nematodes Caenorhabditis elegans (C. elegans). The nematodes were treated with gelsenicine, and subsequently their growth, development, and locomotion behavior were evaluated. The targets of gelsenicine were predicted using PharmMapper. mRNA-seq was performed to verify the predicted targets. Intestinal permeability, ROS generation, and lipofuscin accumulation were measured. Additionally, the fluorescence intensities of GFP-labeled proteins involved in oxidative stress and unfolded protein response in endoplasmic reticulum (UPRER) were quantified. As a result, the treatment of gelsenicine resulted in the inhibition of nematode lifespan, as well as reductions in body length, width, and locomotion behavior. A total of 221 targets were predicted by PharmMapper, and 731 differentially expressed genes were screened out by mRNA-seq. GO and KEGG enrichment analysis revealed involvement in redox process and transmembrane transport. The permeability assay showed leakage of blue dye from the intestinal lumen into the body cavity. Abnormal mRNAs expression of gem-4, hmp-1, fil-2, and pho-1, which regulated intestinal development, absorption and catabolism, transmembrane transport, and apical junctions, was observed. Intestinal lipofuscin and ROS were increased, while sod-2 and isp-1 expressions were decreased. Multiple proteins in SKN-1/DAF-16 pathway were found to bind stably with gelsenicine in a predictive model. There was an up-regulation in the expression of SKN-1:GFP, while the nuclear translocation of DAF-16:GFP exhibited abnormality. The UPRER biomarker HSP-4:GFP was down-regulated. In conclusion, the treatment of gelsenicine resulted in the increase of nematode intestinal permeability. The toxicological mechanisms underlying this effect involved the disruption of intestinal barrier integrity, an imbalance between oxidative and antioxidant processes mediated by the SKN-1/DAF-16 pathway, and abnormal unfolded protein reaction.

Involvement of autophagy in mesaconitine-induced neurotoxicity in HT22 cells revealed through integrated transcriptomic, proteomic, and m6A epitranscriptomic profiling.

Background: Mesaconitine (MA), a diester-diterpenoid alkaloid extracted from the medicinal herb Aconitum carmichaelii, is commonly used to treat various diseases. Previous studies have indicated the potent toxicity of aconitum despite its pharmacological activities, with limited understanding of its effects on the nervous system and the underlying mechanisms. Methods: HT22 cells and zebrafish were used to investigate the neurotoxic effects of MA both in vitro and in vivo, employing multi-omics techniques to explore the potential mechanisms of toxicity. Results: Our results demonstrated that treatment with MA induces neurotoxicity in zebrafish and HT22 cells. Subsequent analysis revealed that MA induced oxidative stress, as well as structural and functional damage to mitochondria in HT22 cells, accompanied by an upregulation of mRNA and protein expression related to autophagic and lysosomal pathways. Furthermore, methylated RNA immunoprecipitation sequencing (MeRIP-seq) showed a correlation between the expression of autophagy-related genes and N6-methyladenosine (m6A) modification following MA treatment. In addition, we identified METTL14 as a potential regulator of m6A methylation in HT22 cells after exposure to MA. Conclusion: Our study has contributed to a thorough mechanistic elucidation of the neurotoxic effects caused by MA, and has provided valuable insights for optimizing the rational utilization of traditional Chinese medicine formulations containing aconitum in clinical practice.

A Randomized Crossover Pilot Study Evaluating Glucose Control During Exercise Initiated 1 or 2 h After a Meal in Adults with Type 1 Diabetes Treated with an Automated Insulin Delivery System.

Aims: To assess the safety and efficacy of two exercise sessions performed 60- and 120-min postmeal with a combination of meal bolus reduction and increased glucose target to the automated insulin delivery (AID) system. Methods: A randomized crossover trial in 13 adult participants (6 females) living with type 1 diabetes using AID (A1c = 7.9% ± 0.6%, age = 53.5 ± 15.5 years, T1D duration = 29.0 ± 16.0 years) was conducted. Just before breakfast, at the time of meal bolus, the AID glucose target was increased from 6 to 9 mmol/L, and a meal bolus reduction of 33% was applied. Two 60-min exercise sessions (60% of VO2 peak) were undertaken either 60 min (60EX) or 120 min (120EX) after a standardized breakfast, followed by a 90-min recovery period. Results: The mean reduction in plasma glucose (PG) levels from prebreakfast to postexercise (-0.8 ± 2.4 mmol/L vs. +0.3 ± 2.3 mmol/L, P = 0.082) were similar between 60EX and 120EX. From prebreakfast to postexercise, PG times in range (3.9-10.0 mmol/L; 63.4% ± 43.1% 60EX vs. 51.9% ± 29.7% 120EX, P = 0.219) and time above range (>10.0 mmol/L; 36.3% ± 43.3% 60EX vs. 48.1% ± 29.7% 120EX, P = 0.211) did not differ between interventions. The 60EX attenuated the glucose rise between premeal to pre-exercise (+1.8 ± 2.1 mmol/L 60EX vs. +3.9 ± 2.1 mmol/L 120EX, P = 0.001). No hypoglycemic events (<3.9 mmol/L) occurred during the study. Conclusion: Premeal announcement combining meal bolus reduction and increased glucose target was effective and safe during 60 min of moderate-intensity aerobic exercise, whether exercise onset was 60 or 120 min following a meal. Clinical Trial Registration No.: NCT04031599.

Efficacy of Treatment of Nonsevere Hypoglycemia in Adults With Type 1 Diabetes Using Oral Carbohydrates During Automated Insulin Delivery With and Without Glucagon.

OBJECTIVES: Self-management guidelines for nonsevere hypoglycemia (NS-H) in type 1 diabetes recommend 15 g of simple carbohydrates (CHO) at 15-minute intervals. Because automated insulin delivery (AID) preventively reduces or suspends insulin infusion for imminent hypoglycemia, we aimed to determine whether guidelines were excessive during AID. METHODS: This work was a secondary analysis of NS-H episodes during inpatient single-hormone (insulin) or dual-hormone (insulin and glucagon) AID trials with standardized CHO treatment protocols. RESULTS: Forty NS-H episodes occurred: 15 during single-hormone arms (2 trials) and 25 during dual-hormone arms (5 trials). At NS-H treatment T0min, plasma glucose (PG) level was 3.1±0.6 mmol/L, corresponding to a sensor value of 3.6±0.6 mmol/L. Fifteen minutes after CHO consumption, PG increased by 0.9±0.8 mmol/L, recovering 45% of episodes to a safe PG of ≥4.0 mmol/L. With repeated CHO consumption, time to recovery was 21.4±15.7 minutes without rebound hyperglycemia; PG 1 hour after initial CHO was 5.9±2.0 mmol/L. Outcome differences between single-hormone and dual-hormone systems were not statistically significant, except for higher insulin and glucagon levels and less repeated treatments in dual-hormone AID. PG and glucagon levels at T0min were positively associated with increase in PG at T15min and negatively associated with time to recovery. CONCLUSIONS: NS-H self-management CHO 15-g/15-minute guidelines were neither excessive nor optimal during AID. There is a need to examine data with different AID systems to optimize treatment recommendations.

Characteristics associated with having a hemoglobin A1c ≤ 7 % (≤53 mmol/mol) among adults with type 1 diabetes using an automated insulin delivery system.

BACKGROUND: We aim to investigate which characteristics are associated with having an HbA1c ≤ 7 % (≤53 mmol/mol) among adult automated insulin delivery (AID) users living with type 1 diabetes (T1D). METHODS: Cross-sectional study using data from the T1D BETTER registry. INCLUSION CRITERIA: aged ≥ 18 years old, using a commercial AID system, and with a reported HbA1c range value. Participants were divided into two groups (HbA1c ≤ 7 % group, N = 57; and HbA1c > 7 % group, N = 74). RESULTS: A total of 131 participants were included: 61.8 % females, median age (Q1-Q3) was 43.0 (30.0, 55.0) years, and median duration of T1D was 24.0 (16.0, 36.0) years. Logistic regression analysis suggested that participants with a bachelor's degree or above were more likely (OR 3.04, 95 %CI 1.22, 7.58; P = 0.017) and with a longer duration of pump use were less likely (OR 0.90, 95 %CI 0.84, 0.98; P = 0.009) to report an HbA1c ≤ 7 % when using an AID, after adjusting for age, sex, body mass index, and annual household income. CONCLUSIONS: Our study indicates that among AID users, in order to maximize benefits, additional support is needed for those who do not have a bachelor's degree and/or who have been using an insulin pump for a long time.

Gender differences in reported frequency and consequences of hypoglycemia among adults living with type 1 diabetes: Results from the BETTER registry.

AIMS: To evaluate the frequency and consequences of level 2 (L2H, glucose level < 3.0 mmol/L with autonomous management) and level 3 hypoglycemia (L3H requiring external assistance to treat), in adults living with type 1 diabetes (T1D), while investigating the role of gender. METHODS: Cross-sectional analysis of self-reported retrospective data from a Canadian registry of 900 adults living with T1D using logistic regression models adjusted for age, T1D management modalities, hypoglycemia history, and validated patient-reported outcomes scales. Changes in diabetes management, seeking healthcare resources, and impacts on daily well-being were explored. RESULTS: Of the 900 adults (66% women, mean age 43.7 ± 14.8 years, mean T1D duration 25.5 ± 14.6 years), 87% used wearable diabetes technology. L3H in the past year was reported by 15% participants, similar between genders. Women reported more L2H than men (median (Q1, Q3): 4 (2, 10) vs 3 (1,8), p = 0.015), and were more likely to report persistent fatigue after both L2H and L3H (Odds ratio [95% confidence interval]: 1.95 [1.16, 3.28] and 1.86 [1.25, 2.75], respectively) and anxiety (1.70 [1.05, 2.75]) after a L3H. CONCLUSIONS: The findings suggest taking a gender-based differential approach when addressing hypoglycemia and its various consequences for people living with T1D.

Influence of severe hypoglycemia definition wording on reported prevalence in adults and adolescents with type 1 diabetes: a cross-sectional analysis from the BETTER patient-engagement registry analysis.

AIMS: Compare the self-reported prevalence of severe hypoglycemia (level-3-H) in people with type 1 diabetes (PWT1D) according to two wording of definition: by the International Hypoglycemia Study Group (IHSG) and an alternate simplified version developed by patient-partners (PP). METHODS: Cross-sectional study (PWT1D > = 14 years) self-reporting risk factors, patient-year incidence and annual prevalence of level-3-H were defined according to either IHSG's wording (low sugar levels requiring help from another person, or use of glucagon, or hospitalization, or loss of consciousness) or with an alternative simpler wording developed by PP (low sugar levels that you would have been unable to treat). RESULTS: Among 1430 eligible participants, in the last 12 months, the annual prevalence of level-3-H (IHSG: 242/100 vs. PP: 231/100 patient-years, p = 0.229) and median number of episodes (IHSG: 2.0 [1-3] vs. PP: 1.0 [1-3], p = 0.359) were similar. The prevalence of participants reporting hypoglycemia in the past year was higher with IHSG wording (13.5% vs. 10.5%; p < 0.001); this difference was significantly (p < 0.001) larger among patients with impaired awareness of hypoglycemia. Association of both definitions with level-3-H risk factors was comparable. CONCLUSIONS: The level-3-H episodes by PP and IHSG wording were comparable. The simplicity of PP wording may allow better mutual understanding between patients and healthcare team. TRIAL REGISTRATION: NCT03720197 (registered on October 19th 2018).

Mechanically Robust and Room Temperature Self-Healing Ionogel Based on Ionic Liquid Inhibited Reversible Reaction of Disulfide Bonds.

Although highly desired, it is difficult to develop mechanically robust and room temperature self-healing ionic liquid-based gels (ionogels), which are very promising for next-generation stretchable electronic devices. Herein, it is discovered that the ionic liquid significantly reduces the reversible reaction rate of disulfide bonds without altering its thermodynamic equilibrium constant via small molecule model reaction and activation energy evolution of the dissociation of the dynamic network. This inhibitory effect would reduce the dissociated units in the dynamic polymeric network, beneficial for the strength of the ionogel. Furthermore, aromatic disulfide bonds with high reversibility are embedded in the polyurethane to endow the ionogel with superior room temperature self-healing performance. Isocyanates with an asymmetric alicyclic structure are chosen to provide optimal exchange efficiencies for the embedded disulfide bonds relative to aromatic and linear aliphatic. Carbonyl-rich poly(ethylene-glycol-adipate) diols are selected as soft segments to provide sufficient interaction sites for ionic liquids to endow the ionogel with high transparency, stretchability, and elasticity. Finally, a self-healing ionogel with a tensile strength of 1.65 ± 0.08 MPa is successfully developed, which is significantly higher than all the reported transparent room temperature self-healing ionogel and its application in a 3D printed stretchable numeric keyboard is exemplified.

Cardiovascular Risk Factors and Adherence to Cardiovascular Protection Practice Guidelines in Adults With Type 1 Diabetes: A BETTER Registry Cross-sectional Analysis.

OBJECTIVES: Cardiovascular disease (CVD) is a major cause of morbidity and mortality in people with type 1 diabetes (PWT1D). We assessed cardiovascular risk factors and pharmacologic treatment in a large Canadian cohort of PWT1D. METHODS: This cross-sectional study used data from adult PWT1D in the BETTER registry (n=974). CVD risk factor status, diabetes complications, and treatments (used as proxy for blood pressure and dyslipidemia) were self-reported through online questionnaires. Objective data were available for a subgroup of PWT1D (23%, n=224). RESULTS: Participants were adults (43.9±14.8 years) with a diabetes duration of 23.3±15.2 years; 34.8% reported glycated hemoglobin (A1C) levels of ≤7%, 67.2% reported a very high cardiovascular risk, and 27.2% reported at least 3 CVD risk factors. Most participants received care for CVD in accordance with the Diabetes Canada Clinical Practice Guidelines (DC-CPG), with a median recommended pharmacologic treatment score of 75.0%. However, 3 subgroups of participants with lower adherence (<70%) to DC-CPG were identified: 1) those with microvascular complications and receiving a statin (60.8%, 208 of 342) or renin-angiotensin axis nephroprotective therapy (52.6%, 180 of 342); 2) those aged ≥40 years and receiving statin therapy (67.1%, 369 of 550); and 3) those aged ≥30 years with a diabetes duration of ≥15 years and receiving statin therapy (58.9%, 344 of 584). Among a subgroup of participants with recent laboratory results, only 24.5% of PWT1D (26 of 106) achieved both A1C and low-density lipoprotein cholesterol targets. CONCLUSIONS: Most PWT1D received recommended pharmacologic cardiovascular protection, but specific subgroups required special attention. Target achievement for key risk factors remains suboptimal.

Euphopias G - J, macrocyclic diterpenes with anti-zika virus activity from Euphorbia helioscopia L.

Four new diterpenoids (1-4) and sixteen known diterpenoids (5-20) were purified from the whole plant of Euphorbia helioscopia L. Compounds 1 and 2 were rhamofolane diterpenoids with a 5/7/6 tricyclic systems, compound 3 was a lathyranes diterpenoid, and compound 4 was a jathophanes diterpenoid. The isolated compounds were tested for their cytotoxicity and anti-Zika virus properties, and compounds 9 and 15 showed low cytotoxicity and strong anti-Zika virus properties with EC50 2.63 and 5.94 µM, respectively. Further, the inhibitory effects of compounds on protein levels were determined using Western blotting and immunofluorescence assays.

Single-cell analysis reveals an Angpt4-initiated EPDC-EC-CM cellular coordination cascade during heart regeneration.

Mammals exhibit limited heart regeneration ability, which can lead to heart failure after myocardial infarction. In contrast, zebrafish exhibit remarkable cardiac regeneration capacity. Several cell types and signaling pathways have been reported to participate in this process. However, a comprehensive analysis of how different cells and signals interact and coordinate to regulate cardiac regeneration is unavailable. We collected major cardiac cell types from zebrafish and performed high-precision single-cell transcriptome analyses during both development and post-injury regeneration. We revealed the cellular heterogeneity as well as the molecular progress of cardiomyocytes during these processes, and identified a subtype of atrial cardiomyocyte exhibiting a stem-like state which may transdifferentiate into ventricular cardiomyocytes during regeneration. Furthermore, we identified a regeneration-induced cell (RIC) population in the epicardium-derived cells (EPDC), and demonstrated Angiopoietin 4 (Angpt4) as a specific regulator of heart regeneration. angpt4 expression is specifically and transiently activated in RIC, which initiates a signaling cascade from EPDC to endocardium through the Tie2-MAPK pathway, and further induces activation of cathepsin K in cardiomyocytes through RA signaling. Loss of angpt4 leads to defects in scar tissue resolution and cardiomyocyte proliferation, while overexpression of angpt4 accelerates regeneration. Furthermore, we found that ANGPT4 could enhance proliferation of neonatal rat cardiomyocytes, and promote cardiac repair in mice after myocardial infarction, indicating that the function of Angpt4 is conserved in mammals. Our study provides a mechanistic understanding of heart regeneration at single-cell precision, identifies Angpt4 as a key regulator of cardiomyocyte proliferation and regeneration, and offers a novel therapeutic target for improved recovery after human heart injuries.

An ensemble LSTM-based AQI forecasting model with decomposition-reconstruction technique via CEEMDAN and fuzzy entropy.

Air quality affects people's daily life. Air quality index (AQI) is an essential indicator for controlling air pollution and ensuring public health, whose accurate forecasting can provide timely air pollution warnings and remind people to take protective measures against air pollution in advance. To address this issue, this paper developed a new ensemble learning model for AQI forecasting. In this study, (1) the signal decomposition technique complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) is introduced to decompose the nonlinear and nonstationary AQI history data series into several more regular and more stable subseries firstly. (2) Fuzzy entropy (FE) is selected as the feature indicator to recombine the subseries with similar trends to avoid the problem of over-decomposition and reduce the computing time. (3) An ensemble long short-term memory (LSTM) neural network is established to forecast each reconstructed subseries, whose values are superimposed to predict the AQI value eventually. To validate the predicting performance of the proposed model, daily AQI data of Wuhan, China, dating from January 1, 2019, to February 28, 2022, is used as the experiment case. And comparative analysis is made between the proposed model and other common-used forecasting models. Benchmarking results of the numerical study demonstrate that the proposed model is superior to the other forecasting models with better AQI prediction accuracy.

Comparison of Nocturnal Glucose After Exercise Among Dual-Hormone, Single-Hormone Algorithm-Assisted Insulin Delivery System and Usual Care in Adults and Adolescents Living with Type 1 Diabetes: A Pooled Analysis.

Background: Available studies comparing the efficacy of dual-hormone (DH)-algorithm-assisted insulin delivery (AID), single-hormone (SH)-AID and usual care on postexercise overnight glucose in people with type 1 diabetes (T1D) have had different outcomes. By pooling data from all available studies, we aim to draw stronger conclusions. Methods: Data were pooled from two three-arm, open-label, randomized, controlled, crossover studies. Forty-one adults [median (Q1, Q3) age: 34.0 years (29.5, 51.0), mean HbA1c: 7.5% ± 1.0%] and 17 adolescents with T1D [age: 14.0 (13.0, 16.0), HbA1c: 7.8% ± 0.8%] underwent DH-AID, SH-AID, and usual care. Each intervention involved evening aerobic exercise (60-min). The primary outcome, time in range% (TIR%) overnight (00:00-06:00) postexercise based on continuous glucose monitoring, was compared among treatments using linear mixed effect model or generalized linear mixed model. Results: Among adults, mean TIR% was 94.0% ± 11.9%, 83.1% ± 20.5%, and 65.1% ± 37.0% during DH-AID, SH-AID, and usual care intervention, respectively (P < 0.05 for all between-group comparisons). DH-AID was superior to SH-AID and usual care, and SH-AID was superior to usual care regarding hypoglycemia and hyperglycemia prevention, but not glycemic variability. Among adolescents, DH-AID and SH-AID reduced dysglycemia, but not glycemic variability, better than usual care. Glycemic outcomes were similar between DH-AID and SH-AID. Conclusion: AID systems allow improved postexercise nocturnal glycemic management than usual care for both adults and adolescents. DH-AID was better than SH-AID among adults, but not adolescents.