Association between Longitudinal Change of Sleep Patterns and the Risk of Cardiovascular Diseases.

STUDY OBJECTIVES: To investigate the role of longitudinal change of sleep patterns in the incidence of cardiovascular diseases (CVD). METHODS: Based on UK Biobank, a total of 18,172 participants were enrolled. Five dimensions of healthy sleep including early chronotype, sleep 7-8 hours/day, free of insomnia, no snoring, and no frequent excessive daytime sleepiness were used to generate a healthy sleep score (HSS) ranging from 0 to 5. Corresponding to the HSS of 0-1, 2-3, and 4-5, the poor, intermediate, and healthy sleep pattern were defined. Based on changes of HSS across assessment 1 and 2, we calculated the absolute difference of HSS. For the change of sleep patterns, we categorized five profiles (stable healthy, worsening, stable intermediate, optimizing, and stable poor sleep patterns). The outcomes were incidence of CVD including coronary heart disease (CHD) and stroke. We assessed the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) by Cox hazard models. RESULTS: Compared with participants with stable poor pattern, those who improved their sleep pattern or maintained the healthy sleep pattern had a 26% and 32% lower risk of CVD, respectively. Stable healthy sleep pattern was associated with a 29% and 44% reduced risk of CHD and stroke. Per unit longitudinal increment of the HSS was related to an 8% lower risk of CVD and CHD. Compared with individuals with constant HSS, those with decreased HSS had a 13% higher risk of developing CVD. CONCLUSION: Optimizing sleep pattern and maintaining the healthy sleep pattern may reduce the risk of CVD.

Statins improve cardiac endothelial function to prevent heart failure with preserved ejection fraction through upregulating circRNA-RBCK1.

Heart failure with preserved ejection fraction (HFpEF) is associated with endothelial dysfunction. We have previously reported that statins prevent endothelial dysfunction through inhibition of microRNA-133a (miR-133a). This study is to investigate the effects and the underlying mechanisms of statins on HFpEF. Here, we show that statins upregulate the expression of a circular RNA (circRNA-RBCK1) which is co-transcripted with the ring-B-box-coiled-coil protein interacting with protein kinase C-1 (RBCK1) gene. Simultaneously, statins increase activator protein 2 alpha (AP-2α) transcriptional activity and the interaction between circRNA-RBCK1 and miR-133a. Furthermore, AP-2α directly interacts with RBCK1 gene promoter in endothelial cells. In vivo, lovastatin improves diastolic function in male mice under HFpEF, which is abolished by loss function of endothelial AP-2α or circRNA-RBCK1. This study suggests that statins upregulate the AP-2α/circRNA-RBCK1 signaling to suppress miR-133a in cardiac endothelial cells and prevent diastolic dysfunction in HFpEF.

Association of change in cardiovascular health based on life's essential 8 with incident cardiovascular disease.

Objective: To evaluate whether and to what extent changes in cardiovascular health (CVH) based on life's essential 8 (LE8) are associated with incident cardiovascular disease (CVD). Methods: A total of 7,194 participants were derived from UK Biobank. CVH was evaluated using a modified version of LE8. Participants were classified into three groups according to their LE8 score: high CVH (LE8 score≥80), moderate CVH (50≤LE8 score<80), and low CVH (LE8 score<50). Changes in CVH between 2006/2010 and 2012/2013 were analyzed. Results: During a median of 10.3 years of follow-up, CVD was observed in 597 participants. Compared to the consistent moderate group, the moderate to low group was associated with about 128 % increased risk of CVD (Hazard ratio [HR]: 2.28; 95 % confidence interval [CI]: 1.61, 3.23), and the relevant HR (95 % CI) was 2.19 (1.46, 3.29) for the consistent low group; no statistically significant results were observed in the other groups. Moreover, no statistically significant exposure-response association between absolute change in LE8 score and incident CVD was documented (Poverall=0.15). Conclusion: Change in CVH based on LE8 was associated with the risk of CVD; however, the relationship varied widely in different CVH change patterns.

Parental cardiometabolic multimorbidity and subsequent cardiovascular incidence in middle-aged adults: A prospective cohort study.

Background: The prevalence of cardiometabolic multimorbidity, defined as the coexistence of two or three cardiometabolic diseases (CMDs), including coronary heart disease (CHD), diabetes, and stroke, has increased rapidly in recent years, but the additive association between parental cardiometabolic multimorbidity and cardiovascular incidence in middle-aged adults remains unclear. Methods: All the data analysed in this study were derived from the UK Biobank, and a total of 71,923 participants aged 40-55 years old without CVD were included in the main analyses. A weighted score was developed and grouped participants into four parental CMDs patterns: non-CMD, low burden, middle burden, and high burden. Cox proportional hazard models were used to estimate the associations between parental CMDs pattern and CVD incidence before 65 years old. Improvement in CVD risk prediction by adding parental CMDs pattern to a basic model was evaluated. Results: Among the 71,923 participants, 3070 CVD events were observed during a median 12.04 years of follow-up. Compared to non-CMD groups, adults in high burden group had a 94% (73-117%) increased risk of CVD. The restricted cubic spline analysis revealed an exposure-response association between parental CMDs burden and risk of CVD (Pnonlinear = 0.24). Additionally, models involving parental CMDs pattern showed slightly improvements in CVD risk prediction, especially for CHD. Conclusion: An increased burden of parental CMDs was associated with an increased risk of CVD incidence in middle-aged adults. Parental CMDs pattern may provide valuable information in primary prevention of CVD in middle-aged adults.

Social isolation and loneliness with risk of cardiometabolic multimorbidity: A prospective cohort study from UK Biobank.

The pandemic of the coronavirus disease 2019 resulted in an increased prevalence of social isolation and loneliness. Cox proportional hazards regression was used to test the association between social isolation/loneliness, multiple cardiometabolic diseases (CMDs) and cardiometabolic multimorbidity (CMM). In the multivariable adjusted models, compared with the least isolated, the most isolated had independently associated with CMD (HR 1.07, 95% CI 1.03 to 1.11) and CMM (HR 1.24, 95% CI 1.12 to 1.36) in stage I, and CMM in stage II (HR 1.14, 95% CI 1.05 to 1.23). Compared with those with the least loneliness, those who with most loneliness had about 20% increased risk of CMD and 29% increased risk of CMM in stage I. Those with the most loneliness were also significantly associated with increased CMM risk (HR 1.30, 95% CI 1.19 to 1.42) in stage II. This study revealed the associations of social isolation/loneliness with CMD and CMM.

Chelation-directed interface engineering of in-place self-cleaning membranes.

Water-energy sustainability will depend upon the rapid development of advanced pressure-driven separation membranes. Although energy-efficient, water-treatment membranes are constrained by ubiquitous fouling, which may be alleviated by engineering self-cleaning membrane interfaces. In this study, a metal-polyphenol network was designed to direct the armorization of catalytic nanofilms (ca. 18 nm) on inert polymeric membranes. The chelation-directed mineralized coating exhibits high polarity, superhydrophilicity, and ultralow adhesion to crude oil, enabling cyclable crude oil-in-water emulsion separation. The in-place flux recovery rate exceeded 99.9%, alleviating the need for traditional ex situ cleaning. The chelation-directed nanoarmored membrane exhibited 48-fold and 6.8-fold figures of merit for in-place self-cleaning regeneration compared to the control membrane and simple hydraulic cleaning, respectively. Precursor interaction mechanisms were identified by density functional theory calculations. Chelation-directed armorization offers promise for sustainable applications in catalysis, biomedicine, environmental remediation, and beyond.

Genome-wide association study of cardiometabolic multimorbidity in the UK Biobank.

Considering the high prevalence and poor prognosis of cardiometabolic multimorbidity (CMM), identifying causal factors and actively implementing preventive measures is crucial. However, Mendelian randomization (MR), a key method for identifying the causal factors of CMM, requires knowledge of the effects of SNPs on CMM, which remain unknown. We first analyzed the genetic overlap of single cardiometabolic diseases (CMDs) using the latest genome-wide association study (GWAS) for evidential support and comparison. We observed strong positive genetic correlations and shared loci among all CMDs. Further, GWAS and post-GWAS analyses of CMM were performed in 407 949 European ancestry individuals from the UK Biobank. Eleven loci and 12 lead SNPs were identified. By comparison, we found these SNPs were a subset of SNPs associated with CMDs, including both shared and non-shared SNPs. Then, the polygenic risk score model predicted the risk of CMM (C-index = 0.62) and we identified candidate genes related to lipid metabolism and immune function. Finally, as an example, two-sample MR analysis based on the GWAS revealed potential causal effects of total cholesterol, serum urate, body mass index, and smoking on CMM. These results provide a basis for future MR research and inspire future studies on the mechanism and prevention of CMM.

S-nitrosylation of AMPKγ impairs coronary collateral circulation and disrupts VSMC reprogramming.

Collateral circulation is essential for blood resupply to the ischemic heart, which is dictated by the contractile phenotypic restoration of vascular smooth muscle cells (VSMC). Here we investigate whether S-nitrosylation of AMP-activated protein kinase (AMPK), a key regulator of the VSMC phenotype, impairs collateral circulation. In rats with collateral growth and development, nitroglycerin decreases coronary collateral blood flow (CCBF), inhibits vascular contractile phenotypic restoration, and increases myocardial infarct size, accompanied by reduced AMPK activity in the collateral zone. Nitric oxide (NO) S-nitrosylates human recombinant AMPKγ1 at cysteine 131 and decreases AMP sensitivity of AMPK. In VSMCs, exogenous expression of S-nitrosylation-resistant AMPKγ1 or deficient NO synthase (iNOS) prevents the disruption of VSMC reprogramming. Finally, hyperhomocysteinemia or hyperglycemia increases AMPKγ1 S-nitrosylation, prevents vascular contractile phenotypic restoration, reduces CCBF, and increases the infarct size of the heart in Apoe-/- mice, all of which is rescued in Apoe-/-/iNOSsm-/- mice or Apoe-/- mice with enforced expression of the AMPKγ1-C130A mutant following RI/MI. We conclude that nitrosative stress disrupts coronary collateral circulation during hyperhomocysteinemia or hyperglycemia through AMPK S-nitrosylation.

Assessment of Bidirectional Relationships between Frailty and Mental Disorders: A Bidirectional Mendelian Randomization Study.

OBJECTIVES: Although observational studies have reported the association between frailty and mental disorders, the causality remains unclear. We aimed to evaluate the bidirectional causal association between frailty levels and mental disorders using a 2-sample Mendelian randomization (MR) analysis. DESIGN: A bidirectional, 2-sample Mendelian randomization (MR) analysis. SETTING AND PARTICIPANTS: Instrumental variables were obtained from large-scale genome-wide association study (GWAS) of a European-descent population for frailty index (FI, n = 175,226), Fried Frailty Score (FFS, n = 386,565), major depressive disorder (MDD, n = 674,452), bipolar disorder (n = 353,899), anxiety and stress-related disorder (ASRD, n = 31,880), and schizophrenia (n = 127,906). METHODS: Two-sample MR analyses were conducted using inverse variance-weighted method, with sensitivity analyses using MR-Egger, weighted median, and simple median methods. RESULTS: Per SD increase in genetically predicted FI and FFS increased the risk of MDD [odds ratio (OR) 1.56, 95% CI 1.27-1.94, P = 3.65 × 10-5, and OR 1.67, 95% CI 1.26-2.20, P = 3.02 × 10-4, respectively]. Per-SD increase in genetically predicted FI also increased the risk of ASRD (OR 2.76, 95% CI 1.36-5.60, P = .005). No significant effect was observed for frailty levels on the risk of bipolar disorder and schizophrenia. In the reverse direction, genetically predicted MDD was associated with higher FI (ß 0.182, 95% CI 0.087-0.277, P = 1.79 × 10-4) and FFS (ß 0.121, 95% CI 0.087-0.155, P = 4.43 × 10-12). No reliable evidence supported the effects of genetically predicted bipolar disorder, ASRD, or schizophrenia on frailty levels. CONCLUSIONS AND IMPLICATIONS: A bidirectionally causal association exists between frailty levels and MDD, and higher FI is associated with a higher risk of ASRD. No reliable evidence suggested the causal associations of other mental disorders with frailty. Our findings provided evidence for introduction of psychological-related strategies in management of frailty.

A "Mesh Scaffold" that regulates the mechanical properties and restricts the phase transition-induced volume change of the PNIPAM-based hydrogel for wearable sensors.

Poly(N-isopropylacrylamide) (PNIPAM) is capable of improving the reversibility and responsiveness of flexible electronics. However, its phase transition-induced volume variation and poor adhesiveness remain limitations for expending its applications. Herein, a pressure-sensitive adhesive (PSA), which is a type of mesh scaffold, is constructed inside the network of PNIPAM, providing the hydrogel with a constant volume in response to different temperatures, in situ tunable mechanical properties, and superior adhesiveness. The reversible density of the mesh scaffold adjusts the aggregation state of the hydrogel chains, whereupon it is capable of changing its mechanical modulus from 6.7 kPa to 45.3 kPa. This mechanical mechanism contributes to hydrogel-based flexible devices for multiple applications, especially in pressure-related sensors. The mesh scaffold restricts the phase-transition-induced volume variation, which allows the hydrogel sensor to stably monitor the external pressure at various temperatures. The high adhesion enables the effective interfacial interaction with the skin, avoiding the loss of sensing signals during the detection of human body movements. When it is assembled into an electronic device, it can transmit information and recognize sign language via Morse code. Thus, herein, we report a hydrogel sensor that is promising for pressure detection in temperature-unstable environments, especially for managing the health of patients who require emergency medical care through sign language recognition.

Establishment of machine learning-based tool for early detection of pulmonary embolism.

BACKGROUND AND OBJECTIVES: Pulmonary embolism (PE) is a complex disease with high mortality and morbidity rate, leading to increasing society burden. However, current diagnosis is solely based on symptoms and laboratory data despite its complex pathology, which easily leads to misdiagnosis and missed diagnosis by inexperienced doctors. Especially, CT pulmonary angiography, the gold standard method, is not widely available. In this study, we aim to establish a rapid and accurate screening model for pulmonary embolism using machine learning technology. Importantly, data required for disease prediction are easily accessed, including routine laboratory data and medical record information of patients. METHODS: We extracted features from patients' routine laboratory results and medical records, including blood routine, biochemical group, blood coagulation routine and other test results, as well as symptoms and medical history information. Samples with a feature loss rate greater than 0.8 were deleted from the original database. Data from 4723 cases were retained, 231 of which were positive for pulmonary embolism. 50 features were retained through the positive and negative statistical hypothesis testing which was used to build the predictive model. In order to avoid identification as majority-class samples caused by the imbalance of sample proportion, we used the method of Synthetic Minority Oversampling Technique (SMOTE) to increase the amount of information on minority samples. Five typical machine learning algorithms were used to model the screening of pulmonary embolism, including Support Vector Machines, Logistic Regression, Random Forest, XGBoost, and Back Propagation Neural Networks. To evaluate model performance, sensitivity, specificity and AUC curve were analyzed as the main evaluation indicators. Furthermore, a baseline model was established using the characteristics of the pulmonary embolism guidelines as a comparison model. RESULTS: We found that XGBoost showed better performance compared to other models, with the highest sensitivity and specificity (0.99 and 0.99, respectively). Moreover, it showed significant improvement in performance compared to the baseline model (sensitivity and specificity were 0.76 and 0.76 respectively). More important, our model showed low missed diagnosis rate (0.46) and high AUC value (0.992). Finally, the calculation time of our model is only about 0.05 s to obtain the possibility of pulmonary embolism. CONCLUSIONS: In this study, five machine learning classification models were established to assess the likelihood of patients suffering from pulmonary embolism, and the XGBoost model most significantly improved the precision, sensitivity, and AUC for pulmonary embolism screening. Collectively, we have established an AI-based model to accurately predict pulmonary embolism at early stage.

Flexible Strain-Sensitive Sensors Assembled from Mussel-inspired Hydrogel with Tunable Mechanical Properties and Wide Temperature Tolerance in Multiple Application Scenarios.

Conductive hydrogels, exhibiting wide applications in electronic skins and soft wearable sensors, often require maturely regulating of the hydrogel mechanical properties to meet specific demands and work for a long-term or under extreme environment. However, in situ regulation of the mechanical properties of hydrogels is still a challenge, and regular conductive hydrogels will inevitably freeze at subzero temperature and easily dehydrate, which leads to a short service life. Herein, a novel adhesive hydrogel (PAA-Dopa-Zr4+) capable of strain sensing is proposed with antifreezing, nondrying, strong surface adhesion, and tunable mechanical properties. 3,4-Dihydroxyphenyl-l-alanine (l-Dopa)-grafted poly(acrylic acid) (PAA) and Zr4+ ion are introduced into the hydrogel, which broadly alters the mechanical properties via tuning the in situ aggregation state of polymer chains by ions based on the complexation effect. The catechol groups of l-Dopa and viscous glucose endow the hydrogel with high adhesiveness for skin and device interface (including humid and dry environments) and exhibit an outstanding temperature tolerance under extreme wide temperature spectrum (-35 to 65 °C) or long-lasting moisture retention (60 days). Furthermore, this PAA-Dopa-Zr4+ can be assembled as a flexible strain-sensitive sensor to detect human motions based on specific mechanical properties requirements. This work, enabling superior adhesive and temperature tolerance performance and broad mechanical tenability, presents a new paradigm for numerous applications to wearable sensing and personalized healthcare monitoring.

Computed tomographic manifestations of celiac ganglia between hypertensive and non-hypertensive population.

The celiac ganglion (CG) is associated with the sympathetic nervous system (SNS) and plays an important role in the pathogenesis of hypertension. The characteristics of the CG in patients with hypertension remain unknown. The aim of our study was to explore the differences in celiac ganglia (CGs) characteristics between hypertensive and non-hypertensive populations using computed tomography (CT). CGs manifestations on multidetector row CT in 1003 patients with and without hypertension were retrospectively analyzed. The morphological characteristics and CT values of the left CGs were recorded. The CT values of the ipsilateral adrenal gland (AG) and crus of the diaphragm (CD) were also measured. The left CG was located between the left AG and CD, and most CGs were long strips. The frequency of visualization of the left CGs was higher in the hypertension group than in the non-hypertension group (p < .05). There were no significant differences in the maximum diameter, size, and shape ratio of the left CGs between the two groups (p > .05). Except for the left CG in the arterial phase, the CT values of the left CG and AG in the non-hypertensive group were higher than those in the hypertension group (p < .05). The venous phase enhancement of the left CG in the non-hypertension group was significantly higher than that in the hypertension group (p < .05). Our findings reveal that CGs have characteristic manifestations in the hypertensive population. As important targets of the SNS, CGs have the potential to regulate blood pressure.

Projecting future aboveground carbon sequestration rate of alpine forest on the eastern Tibetan Plateau in response to climate change.

The aboveground carbon sequestration rate (ACSR) of forests serves as an indicator of their carbon sequestration capacity over time, providing insights into the potential carbon sequestration capacity of forest ecosystems. To explore the long-term Spatiotemporal variation of ACSR in the transitional ecotone of the eastern Tibetan Plateau under climate change scenarios, we utilized a forest landscape model that was parameterized with forest inventory data from the eastern Tibetan Plateau to simulate this ecological function changes. The study found that climate warming had significant effect on forests ACSR in different types of forests. ACSR was significantly reduced (p<0.05) in cold temperate coniferous and temperate coniferous forests, whereas it was significantly increased in deciduous broad-leaved forests. However, the impact of climate warming on evergreen broad-leaved forests was found to be negligible. At the species level, climate warming has mostly suppressed the ACSR of coniferous trees, except for Chinese hemlock. The main dominant species, spruce and fir, have been particularly affected. Conversely, the ACSR of most broad-leaved trees has increased due to climate warming. In addition, at the landscape scale, the ACSR within this region is expected to experience a steady decline after 2031s-2036s. Despite the effects of climate warming, this trend is projected to persist. In conclusion, the forests ACSR in this region will be significantly affected by future climate warming. Our research indicates that climate warming will have a noticeable suppressive effect on conifers. It is imperative that this factor be taken into account when devising forest management plans for the future in this region.

Omentin-1 drives cardiomyocyte cell cycle arrest and metabolic maturation by interacting with BMP7.

Mammalian cardiomyocytes (CMs) undergo maturation during postnatal heart development to meet the increased demands of growth. Here, we found that omentin-1, an adipokine, facilitates CM cell cycle arrest and metabolic maturation. Deletion of omentin-1 causes mouse heart enlargement and dysfunction in adulthood and CM maturation retardation in juveniles, including delayed cell cycle arrest and reduced fatty acid oxidation. Through RNA sequencing, molecular docking analysis, and proximity ligation assays, we found that omentin-1 regulates CM maturation by interacting directly with bone morphogenetic protein 7 (BMP7). Omentin-1 prevents BMP7 from binding to activin type II receptor B (ActRIIB), subsequently decreasing the downstream pathways mothers against DPP homolog 1 (SMAD1)/Yes-associated protein (YAP) and p38 mitogen-activated protein kinase (p38 MAPK). In addition, omentin-1 is required and sufficient for the maturation of human embryonic stem cell-derived CMs. Together, our findings reveal that omentin-1 is a pro-maturation factor for CMs that is essential for postnatal heart development and cardiac function maintenance.

Frailty, an Independent Risk Factor in Progression Trajectory of Cardiometabolic Multimorbidity: A Prospective Study of UK Biobank.

BACKGROUND: Although frailty was associated with cardiometabolic diseases (CMDs, including coronary heart disease, stroke, and diabetes here), there was no systematic analyses estimating its role in incidence, progression, and prognosis of cardiometabolic multimorbidity (CMM). METHODS: We included 351 205 participants without CMDs at baseline in UK Biobank. Occurrences of first CMD, CMM, and death were recorded. We used multistate models to assess transition-specific role of baseline frailty measured by frailty phenotype and frailty index in CMM progression trajectory from no disease to single CMD, CMM, and death. Association between changes in frailty and outcomes was investigated among 17 264 participants. RESULTS: Among 351 205 participants (44.0% male, mean age 56.55 years), 8 190 (2.3%) had frail phenotype, and 13 615 (3.9%) were moderate/severe frail according to the frailty index. During median follow-up of 13.11 years, 41 558 participants experienced ≥1 CMD, 4 952 had CMM, and 20 670 died. In multistate models, frail phenotype-related hazard ratios were 1.94 and 2.69 for transitions from no CMD to single disease and death, 1.63 and 1.67 for transitions from single CMD to CMM and death, and 1.57 for transitions from CMM to death (all p < .001). Consistent results were observed for frailty index. Improvement of frailty reduced the risk of CMD progression and death. CONCLUSIONS: Frailty is an independent risk factor for all transitions of CMM progression trajectory. Frailty-targeted management is a potential strategy for primary and secondary prevention of CMM beyond chronological age.

High-resolution visualization of pial surface vessels by flattened whole mount staining.

Understanding development of the cerebral vasculature is essential for the central nervous system (CNS) research and therapeutic developments. Here, we developed a simple, convenient, and fast method-the flattened cortex whole mount (FCWM) technique-for imaging of pial cerebral vessels. FCWM involves dissection of the whole cerebral cortex followed by flattening, sectioning and application of CLARITY technology. Compared to conventional methods, FCWM offers several advantages including (1) high-resolution visualization of the whole cortex pial surface vessel structures and distributions; (2) precise localization of a particular blood vessel, allowing observations of a desired blood vessel during normal development or in disease settings; (3) compatibility with confocal imaging. Application of FCWM for examination of cerebral vasculature during postnatal development or in stroke settings allowed us to demonstrate that cerebral blood vessels manifest type-specific maturation and remodeling which are linked to the rate of endothelial proliferation.

The TRPM7 channel reprograms cellular glycolysis to drive tumorigenesis and angiogenesis.

Cancer or endothelial cells preferably catabolize glucose through aerobic glycolysis rather than oxidative phosphorylation. Intracellular ionic signaling has been shown to regulate glucose metabolism, but the underlying ion channel has yet to be identified. RNA-seq, metabolomics and genetic assay revealed that the TRPM7 channel regulated cellular glycolysis. Deletion of TRPM7 suppressed cancer cell glycolysis and reduced the xenograft tumor burden. Deficiency of endothelial TRPM7 inhibited postnatal retinal angiogenesis in mice. Mechanistically, TRPM7 transcriptionally regulated the solute carrier family 2 member 3 (SLC2A3, also known as GLUT3) via Ca2+ influx-induced calcineurin activation. Furthermore, CREB-regulated transcription coactivator 2 (CRTC2) and CREB act downstream of calcineurin to relay Ca2+ signal to SLC2A3 transcription. Expression of the constitutively active CRTC2 or CREB in TRPM7 knockout cell normalized glycolytic metabolism and cell growth. The TRPM7 channel represents a novel regulator of glycolytic reprogramming. Inhibition of the TRPM7-dependent glycolysis could be harnessed for cancer therapy.

Preparation Optimization of CFRP and EPDM Composite by the Co-Curing Method.

As the requirements of aerospace technology become more rigorous, the performance of solid rocket motor (SRM) cases needs to be further optimized. In the present study, a co-curing technique was used to fabricate carbon fiber reinforced polymer (CFRP)/ethylene-propylene-diene monomer (EPDM) composites whereby the properties of CFRP/EPDM composites were adjusted by varying the temperature, heating time and type of vulcanizing agent to obtain the optimum manufacturing process. The results of crosslink density (3.459 × 10-4 mol/cm3) tested by nuclear magnetic resonance (NMR), a 90° peel strength test (2.342 N/mm), and an interlaminar shear test (ILSS = 82.08 MPa) demonstrated that the optimum mechanical properties of composites were obtained under the temperature 160 °C heated for 20 min with the curing agent DCP/S. The interfacial phase and bonding mechanism of composites were investigated by scanning electron microscopy (SEM). Thermogravimetric analysis (TGA) further indicated that EPDM/DCP/S had favorable thermal stability. This will provide valuable recommendations for the optimization of the SRM shell preparation process.

The association between sleep characteristics and the risk of all-cause mortality among individuals with cardiometabolic multimorbidity: a prospective study of UK Biobank.

STUDY OBJECTIVES: To investigate the implications of both sleep factors and sleep patterns on the prognosis of cardiometabolic multimorbidity. METHODS: From UK Biobank, individuals with cardiometabolic multimorbidity , defined as the coincidence of at least 2 cardiometabolic diseases (hypertension, diabetes mellitus, coronary heart disease, and stroke) were included in this study. Four low-risk sleep factors, including early chronotype, sleep 7-8 h/d, free of insomnia, and no frequent excessive daytime sleepiness, were used to generate a healthy sleep score ranging from 0 to 4. Participants with a score of 0-1, 2, 3-4 were clustered into groups with poor, intermediate, and healthy sleep pattern, respectively. We assessed the adjusted hazard ratios and 95% confidence intervals for all-cause mortality using the Cox proportional hazards model. RESULTS: Among included 35,757 participants, the mean age (standard deviation)) was 61.82 (6.3) years. After full adjustment, early chronotype, sleep 7-8 h/d, no frequent excessive daytime sleepiness, and free of insomnia were independently associated with 8%, 12%, 11%, and 8% lower risk of all-cause mortality among all persons with cardiometabolic multimorbidity. We found the fully adjusted hazard ratio (95% confidence interval) for all-cause mortality was 0.90 (0.88-0.92) for a 1-point increase in the healthy sleep score. Compared with the reference group, participants with the intermediate and healthy sleep pattern had 9% and 23% lower risk of all-cause death, respectively, in the fully adjusted model. CONCLUSIONS: A healthy sleep pattern combining 4 low-risk sleep factors could be regarded as a healthy lifestyle for individuals with cardiometabolic multimorbidity to lower the risk of all-cause mortality. CITATION: He L, Ma T, Cheng X, Bai Y. The association between sleep characteristics and the risk of all-cause mortality among individuals with cardiometabolic multimorbidity: a prospective study of UK Biobank. J Clin Sleep Med. 2023;19(4):651-658.