Correlation between Anterior Mitral Annular Plane Systolic Excursion and Left Atrial Appendage Stasis in Patients with Nonvalvular Atrial Fibrillation.

Background: Atrial fibrillation (AF) can lead to a decline in left atrial appendage (LAA) function, potentially increasing the likelihood of LAA thrombus (LAAT) and spontaneous echo contrast (SEC). Measuring LAA flow velocity through transesophageal echocardiography (TEE) is currently the primary method for evaluating LAA function. This study aims to explore the potential correlation between anterior mitral annular plane systolic excursion (aMAPSE) and LAA stasis in patients with non-valvular atrial fibrillation (NVAF). Methods: A total of 465 patients with NVAF were enrolled between October 2018 and November 2021. Transthoracic echocardiography (TTE) and TEE were performed before scheduled electrical cardioversion. Propensity score matching (PSM) was used to balance confounders between the groups with and without LAAT/dense SEC. Results: Patients in the LAAT/dense SEC group showed increased left atrial (LA) diameter, LAA area, alongside reduced left ventricular ejection fraction (LVEF), LAA velocity, conjunction thickening ratio, aMAPSE, and LAA fraction area change (FAC) compared to those in the non-LAAT/dense SEC group. Multivariate logistic regression analysis identified aMAPSE and LAA FAC as independent predictors for LAAT/dense SEC. Specifically, an aMAPSE of < 6.76 mm and an LAA FAC of < 29.65% predicted LAAT/dense SEC with high diagnostic accuracy, demonstrated by an area under the curve (AUC) of 0.81 (sensitivity 0.81, specificity 0.80) for aMAPSE, and an AUC of 0.80 (sensitivity 0.70, specificity 0.84) for LAA FAC. Conclusions: Both aMAPSE and LAA FAC independently correlated with and accurately predict LAAT/dense SEC. Incorporating aMAPSE into routine TEE evaluations for LAA function alongside LAA flow velocity is recommended.

An infusible biologically active adhesive for chemotherapy-related heart failure in elderly rats.

Chemotherapy-induced cardiotoxicity with subsequent heart failure (HF) is a major cause of morbidity and mortality in cancer survivors worldwide. Chemotherapy-induced HF is exceptionally challenging as it generally manifests in patients who are typically not eligible for left ventricular device implantation or heart transplantation. To explore alternative treatment strategies for cancer survivors suffering from chemotherapy-induced HF, we developed a minimally invasive infusible cardiac stromal cell secretomes adhesive (MISA) that could be delivered locally through an endoscope-guided intrapericardial injection. To mimic the typical clinical presentation of chemotherapy-induced HF in elder patients, we established an aged rat model in which restrictive cardiomyopathy with sequential HF was induced via consecutive doxorubicin injections. In vitro, we prove that MISA not only enhanced cardiomyocytes proliferation potency and viability, but also inhibited their apoptosis. In vivo, we prove that MISA improved the ventricular contractility indexes and led to beneficial effects on histological and structural features of restrictive cardiomyopathy via promoting cardiomyocyte proliferation, angiogenesis, and mitochondrial respiration. Additionally, we also evaluated the safety and feasibility of MISA intrapericardial delivery in a healthy porcine model with an intact immune system. In general, our data indicates that MISA has a strong potential for translation into large animal models and ultimately clinical applications for chemotherapy-induced HF prior to the final option of heart transplantation.

Factors Influencing the Use and Demand of New Coronavirus Therapy Drugs Among the Adults During COVID-19 in China.

Background: This alteration in the policy of COVID-19 resulted in widespread infections throughout China. Most people only need some antiviral drugs such as lopinavir/ritonavir or Chinese herbal preparations for treatment. In this context, the lack of drug knowledge and inadequate drug availability are evident. This study aims to explore the factors influencing drug use and demand during the COVID-19 epidemic. Methods: This study used quota sampling based on gender, age, and place of residence to perform a cross-sectional survey on a sample of 771 adults. The researchers used chi-square tests to understand differences in drug use and demand across characteristics, and binary logistic regression to analyse the influencing factors. Results: The study revealed that 85.9% of the participants used drugs following the COVID-19 infection. Participants with college and above, (OR=2.49, 95% CI=1.27-4.88) annual personal income between 30,000 and 80,000CNY (OR=2.19, 95% CI=1.35-3.55) and over 80,000CNY (OR=1.96, 95% CI=1.05-3.66) were more knowledgeable about using drugs. Gender, (OR=0.69, 95% CI=0.50-0.95) age, (OR=2.11, 95% CI=1.15-3.88) residence, (OR=1.58, 95% CI=1.06-2.37) chronic disease conditions (OR=0.46, 95% CI=0.27-0.78) and infection symptoms (OR=0.60, 95% CI=0.38-0.93) as factors influencing the need for drug delivery services. (P<0.05). Conclusion: Research has revealed that a significant proportion of infected people in China chose drug treatment during COVID-19. Individuals with severe symptoms use more medication and require more drug delivery and storage. Low-education and low-income populations are lacking in drug knowledge, and older adults with underlying medical conditions are more likely to need drug delivery services. Therefore, governments should prioritize vulnerable groups when formulating drug policies and target drug literacy and guidance. In addition, it is recommended that a drug distribution system be set up within the community so that those in need can have quick and easy access to drugs.

Chronic dietary exposure to glyphosate-induced connexin 43 autophagic degradation contributes to blood-testis barrier disruption in roosters.

Glyphosate (GLY) is the most universally used herbicide worldwide and its application has caused extensive pollution to the ecological environment. Increasing evidence has revealed the multi-organ toxicity of GLY in different species, but its male reproductive toxicity in avian species remains unknown. Thus, in vivo and in vitro studies were conducted to clarify this issue. Data firstly showed that chronic GLY exposure caused testicular pathological damage. Intriguingly, we identified and verified a marked down-regulation gap junction gene Connexin 43 (Cx43) in GLY-exposed rooster testis by transcriptome analysis. Cx43 generated by Sertoli cells acts as a key component of blood-testis barrier (BTB). To further investigate the cause of GLY-induced downregulation of Cx43 to disrupt BTB, we found that autophagy activation is revealed in GLY-exposed rooster testis and primary avian Sertoli cells. Moreover, GLY-induced Cx43 downregulation was significantly alleviated by ATG5 knockdown or CQ administration, respectively, demonstrating that GLY-induced autophagy activation contributed to Cx43 degradation. Mechanistically, GLY-induced autophagy activation and resultant Cx43 degradation was due to its direct interaction with ER-α. In summary, these findings demonstrate that chronic GLY exposure activates autophagy to induce Cx43 degradation, which causes BTB damage and resultant reproductive toxicity in roosters.

Cardiac intravoxel incoherent motion diffusion-weighted imaging to assess myocardial microcirculation dysfunction in hypertension.

Background: Myocardial microcirculation dysfunction is the most potent predictor of adverse cardiovascular events in hypertension. The current study aimed to apply intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) to assess hypertension-related microcirculation dysfunction. Methods: In this prospective study, 102 participants were recruited from our hospital and underwent cardiac magnetic resonance (CMR) examination on a 3T scanning system. Hypertensive patients were divided into 3 subgroups based on blood pressure (BP) types. Two experienced CMR radiologists independently analyzed all images, and Bland-Altman analysis was applied to assess intra- and inter-observer reproducibility. Cardiac function indexes and IVIM-DWI parameters were compared between the hypertension and healthy control groups, as well as among the three hypertension subgroups. Results: Totally 62 participants with hypertension and 27 healthy controls were included. 13 participants were excluded for poor quality of IVIM-DWI images. Significantly higher maximal left ventricular wall thickness (10.3±2.0 vs. 8.6±1.4 mm, P<0.001) and left ventricular mass index (49.0±9.1 vs. 42.1±7.5 g/m2, P<0.05) were observed inhypertension group compared with healthy control group. There were significant statistical differences in pseudo diffusion (D*) between them (81.3±16.3 vs. 111.8±18.9 mm2/s, P<0.001), as well as among the three hypertension subgroups (99.4±13.9 vs. 79.7±10.6 vs. 67.1±6.6 mm2/s, P<0.001). Participants with poor quality of IVIM-DWI images had higher heart rates (72.2±10.0 vs. 62.0±8.1 bpm, P<0.001). Conclusions: IVIM-DWI is feasible for quantitatively evaluating myocardial microcirculation dysfunction in hypertension. The D* parameter has a potential value for assessing the severity of microcirculation dysfunction in different BP categories.

Factors associated with psychological insulin resistance among patients with type 2 diabetes in China.

Objective: The aim of this study was to understand the psychological insulin resistance status among Chinese patients with type 2 diabetes and investigate its associated factors in these patients. Methods: A multi-stage stratified random sampling was performed to randomly select patients with type 2 diabetes from the eastern, central, and western regions in Shandong Province, China, and 660 valid questionnaires were collected. Psychological insulin resistance was assessed by the scale of My Opinion on Insulin (MOI). Factors associated with psychological insulin resistance were examined in a binary logistic model. Results: Four-fifths of the patients with type 2 diabetes (82.1%) had psychological insulin resistance. Being female (OR = 1.770, 95% CI: 1.063-2.950, p < 0.05), having a monthly income of greater than 4,000 Renminbi (approximately $1,540) (OR = 0.444, 95% CI: 0.216-0.915, p < 0.05), living with type 2 diabetes for 11 years or more (OR = 0.387, 95% CI: 0.238-0.630, p < 0.05), self-rated poor health (OR = 1.706, 95% CI: 1.092-2.664, p < 0.05), and moderate discrimination against type 2 diabetes (OR = 1.924, 95% CI: 1.166-3.175, p < 0.05) were associated with psychological insulin resistance. Conclusions: The prevalence of psychological insulin resistance among Chinese patients with type 2 diabetes is relatively high. Approaches are needed to address the issue of psychological insulin resistance of type 2 diabetes.

Three-dimensional high-aspect-ratio microarray thick electrodes for high-rate hybrid supercapacitors.

Hybrid supercapacitors (HSCs) with facile integration and high process compatibility are considered ideal power sources for portable consumer electronics. However, as a crucial component for storing energy, traditional thin-film electrodes exhibit low energy density. Although increasing the thickness of thin films can enhance the energy density of the electrodes, it gives rise to issues such as poor mechanical stability and long electron/ion transport pathways. Constructing a stable three-dimensional (3D) ordered thick electrode is considered the key to addressing the aforementioned contradictions. In this work, a manufacturing process combining lithography and chemical deposition techniques is developed to produce large-area and high-aspect-ratio 3D nickel ordered cylindrical array (NiOCA) current collectors. Positive electrodes loaded with nickel-cobalt bimetallic hydroxide (NiOCA/NiCo-LDH) are constructed by electrodeposition, and HSCs are assembled with NiOCA/nitrogen-doped porous carbon (NiOCA/NPC) as negative electrodes. The HSCs exhibits 55% capacity retention with the current density ranging from 2 to 50 mA cm-2. Moreover, it maintains 98.2% of the initial capacity after long-term cycling of 15,000 cycles at a current density of 10 mA cm-2. The manufacturing process demonstrates customizability and favorable repeatability. It is anticipated to provide innovative concepts for the large-scale production of 3D microarray thick electrodes for high-performance energy storage system.

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.

Dynamic evolution of COVID-19 vaccine hesitancy over 2021-2023 among Chinese population: Repeated nationwide cross-sectional study.

Globally, the rollout of COVID-19 vaccine had been faced with a significant barrier in the form of vaccine hesitancy. This study adopts a multi-stage perspective to explore the prevalence and determinants of COVID-19 vaccine hesitancy, focusing on their dynamic evolutionary features. Guided by the integrated framework of the 3Cs model (complacency, confidence, and convenience) and the EAH model (environmental, agent, and host), this study conducted three repeated national cross-sectional surveys. These surveys carried out from July 2021 to February 2023 across mainland China, targeted individuals aged 18 and older. They were strategically timed to coincide with three critical vaccination phases: universal coverage (stage 1), partial coverage (stage 2), and key population coverage (stage 3). From 2021 to 2023, the surveys examined sample sizes of 29 925, 6659, and 5407, respectively. The COVID-19 vaccine hesitation rates increased from 8.39% in 2021 to 29.72% in 2023. Urban residency, chronic condition, and low trust in vaccine developer contributed to significant COVID-19 vaccine hesitancy across the pandemic. Negative correlations between the intensity of vaccination policies and vaccine hesitancy, and positive correlations between vaccine hesitancy and long COVID, were confirmed. This study provides insights for designing future effective vaccination programs for emerging vaccine-preventable infectious X diseases.

Light and Displacement Compensation-Based iPPG for Heart-Rate Measurement in Complex Detection Conditions.

A light and displacement-compensation-based iPPG algorithm is proposed in this paper for heart-rate measurement in complex detection conditions. Two compensation sub-algorithms, including light compensation and displacement compensation, are designed and integrated into the iPPG algorithm for more accurate heart-rate measurement. In the light-compensation sub-algorithm, the measurement deviation caused by the ambient light change is compensated by the mean filter-based light adjustment strategy. In the displacement-compensation sub-algorithm, the measurement deviation caused by the subject motion is compensated by the optical flow-based displacement calculation strategy. A series of heart-rate measurement experiments are conducted to verify the effectiveness of the proposed method. Compared with conventional iPPG, the average measurement accuracy increases by 3.8% under different detection distances and 5.0% under different light intensities.

Changes of cardiac function: cardiac adaptation in patients with hypothyroidism assessed by cardiac magnetic resonance-a meta-analysis.

Objective: The meta-analysis aimed to explore the cardiac adaptation in hypothyroidism patients by cardiac magnetic resonance. Research methods and procedures: Databases including PubMed, Cochrane Library, Embase, CNKI, and Sinomed for clinical studies of hypothyroidism on cardiac function changes. Databases were searched from the earliest data to 15 June 2023. Two authors retrieved studies and evaluated their quality. Review Manager 5.4.1 and Stata18 were used to analyze the data. This study is registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), 202440114. Results: Six studies were selected for further analysis. Five of them reported differences in cardiac function measures between patients with hypothyroidism and healthy controls, and three studies reported cardiac function parameters after treatment in patients with hypothyroidism. The fixed-effect model combined WMD values for left ventricular ejection fraction (LVEF) had a pooled effect size of -1.98 (95% CI -3.50 to -0.44], P=0.01), implying that LVEF was lower in patients with hypothyroidism than in healthy people. Analysis of heterogeneity found moderate heterogeneity (P = 0.08, I² = 50%). WMD values for stroke volume (SV), cardiac index (CI), left ventricular end-diastolic volume index(LVEDVI), left ventricular end-systolic volume (LESVI), and left ventricular mass index(LVMI) were also analyzed, and pooled effect sizes showed the CI and LVEDVI of patients with hypothyroidism ware significantly decrease (WMD=-0.47, 95% CI [-0.93 to -0.00], P=0.05, WMD=-7.99, 95%CI [-14.01 to -1.96], P=0.009, respectively). Patients with hypothyroidism tended to recover cardiac function after treatment [LVEF (WMD = 6.37, 95%CI [2.05, 10.69], P=0.004), SV (WMD = 7.67, 95%CI [1.61, 13.74], P=0.01), CI (WMD = 0.40, 95%CI [0.01, 0.79], P=0.05)], and there was no difference from the healthy controls. Conclusion: Hypothyroidism could affect cardiac function, although this does not cause significant heart failure. It may be an adaptation of the heart to the hypothyroid state. There was a risk that this adaptation may turn into myocardial damage. Cardiac function could be restored after treatment in patients with hypothyroidism. Aggressive levothyroxine replacement therapy should be used to reverse cardiac function. Systematic review registration: https://inplasy.com, identifier (INPLASY202440114).

The Bioinformatic Applications of Hi-C and Linked Reads.

Long-range sequencing grants insight into additional genetic information beyond that which can be accessed by both short reads and modern long-read technology. Several new sequencing technologies are available for long-range datasets such as "Hi-C" and "Linked Reads" with high-throughput and high-resolution genome analysis, and are rapidly advancing the field of genome assembly, genome scaffolding, and more comprehensive variant identification. In this article, we focused on five major long-range sequencing technologies: high-throughput chromosome conformation capture (Hi-C), 10x Genomics Linked Reads, haplotagging, transposase enzyme linked long-read sequencing (TELL-seq), and single tube long fragment read (stLFR). We detailed the mechanisms and data products of the five platforms, introduced several of the most important applications, evaluated the quality of sequencing data from different platforms, and discussed the currently available bioinformatics tools. We hope this work will benefit the selection of appropriate long-range technology for specific biological studies.

Full prescribed performance trajectory tracking control strategy of autonomous underwater vehicle with disturbance observer.

This paper investigates trajectory tracking control of the Autonomous Underwater Vehicle (AUV) with the general uncertainty consisting of model uncertainties and unknown ocean current disturbances. A full prescribed performance control strategy based on disturbance observer is developed, which ensures that the tracking error, the velocity error, and the observation error are all constrained. First, under the case of unmeasurable AUV acceleration, a fixed-time observer is constructed to estimate the general uncertainty, which constrains the observation error within the prescribed accuracy by a prescribed performance observer. Then, based on the performance function and corresponding error transformation, a prescribed performance protocol is designed to realize the trajectory tracking control, so that the observation error, the tracking error, and the velocity error are all constrained within the prescribed accuracy range. Simulation results demonstrate the efficiency of the full prescribed performance control strategy while the AUV tracking control with full state constraints is feasible. Moreover, compared with the other two relevant works, this study improves the observation performance by at least 10 %, both in case of deepwater disturbances and near-surface disturbances.

I Single-Atom Doped P-Rich CoPn Nanocluster@CoP with Enhanced HER.

Constructing I single-atom (ISA) doped CoP electrocatalyst for HER is extremely challenging and has not been reported to date. Herein, an ISA doping-phosphatization strategy is proposed to prepare a novel I single-atom doped P-rich CoPn nanocluster@CoP electrocatalyst (ISA-CoPn/CoP) with enhanced HER performance first. ISA-CoPn/CoP shows a low overpotential of only 44 and 81 mV in 0.5 m H2SO4 solution, to drive a current density of 10 and 100 mA cm-2. ISA and P-rich CoPn nanocluster show unique synergies, which can optimize the H adsorption energy and accelerate the kinetics of HER in the CoP system. The intermediate I─H bond vibration peak is directly observed through in situ Raman testing, demonstrating that ISA doping helps accelerate the HER process. Additionally, the ΔGH of ISA-CoPn/CoP is only 0.05 eV by density functional theory (DFT) calculation, which is conducive to H2 evolution.

Climate change drove the route shift of the ancient Silk Road in two distinct ways.

Although climate change has convincingly been linked to the evolution of human civilization on different temporal scales, its role in influencing the spatial patterns of ancient civilizations has rarely been investigated. The northward shift of the ancient Silk Road (SR) route from the Tarim Basin (TB) to the Junggar Basin during ∼420-850 CE provides the opportunity to investigate the relationship between climate change and the spatial evolution of human societies. Here, we use a new high-resolution chironomid-based temperature reconstruction from arid China, combined with hydroclimatic and historical datasets, to assess the possible effects of climate fluctuations on the shift of the ancient SR route. We found that a cooling/drying climate in the TB triggered the SR route shift during ∼420-600 CE. However, a warming/wetting climate during ∼600-850 CE did not inhibit this shift, but instead promoted it, because of the favorable climate-induced geopolitical conflicts between the Tubo Kingdom and the Tang Dynasty in the TB. Our findings reveal two distinct ways in which climate change drove the spatial evolution of human civilization, and they demonstrate the flexibility of societal responses to climate change.

Freezing Shrinkage Dynamics and Surface Dendritic Growth of Floating Refractory Alloy Droplets in Outer Space.

The freezing shrinkage and dendritic growth are of great importance for various alloys solidified from high-temperature liquids to solids since they dominate microstructure patterns and follow-up processing. However, the microgravity freezing shrinkage dynamics is scarcely explored on the ground as it is hard to suppress the strong natural convection inside liquid alloys. Here, a series of in-orbit solidification experiments is conducted aboard the China Space Station with a long-term stable 10-5 g0 microgravity condition. The highest temperature up to 2265 K together with substantial liquid undercoolings far from a thermodynamically stable state are attained for both Nb82.7Si17.3 and Zr64V36 refractory alloys. Furthermore, the solidification under microgravity of a droplet is simulated to reveal the liquid-solid interface migration, temperature gradient, and flow field. The microgravity solidification process leads to freezing shrinkage cavities and distinctive surface dendritic microstructure patterns. The combined effects of shrinkage dynamics and liquid surface flow in outer space result in the dendrites growing not only along the tangential direction but also along the normal direction to the droplet surface. These space experimental results contribute to a further understanding of the solidification behavior of liquid alloys under a weaker convection condition, which is often masked by gravity on the ground.

Microvascular disease, modifiable risk factor profiles and incident arrhythmias in type 2 diabetes.

BACKGROUND: To assess the roles of diabetic microvascular disease and modifiable risk factors and their combination in the development of arrhythmias. METHODS: We included participants with type 2 diabetes (T2D) who were free of arrhythmias during recruitment in the UK Biobank study. The associations of microvascular disease states (defined by the presence of retinopathy, peripheral neuropathy or chronic kidney disease), four modifiable arrhythmic risk factors (body mass index, smoking, systolic blood pressure and glycosylated haemoglobin) and their joint associations with incident arrhythmias were examined. RESULTS: Among the 25 632 participants with T2D, 1705 (20.1%) of the 8482 with microvascular disease and 2017 (11.8%) of the 17 150 without microvascular disease developed arrhythmias during a median follow-up of 12.3 years. Having any of the three microvascular diseases was associated with a 48% increase in the hazard of developing arrhythmias. Incorporating microvascular disease states into a model alongside 11 traditional risk factors significantly enhanced arrhythmia prediction. Furthermore, individuals with microvascular disease who had optimal levels of zero to one, two, three or four arrhythmic risk factors showed an HR of 2.05 (95% CI 1.85, 2.27), 1.67 (95% CI 1.53, 1.83), 1.35 (95% CI 1.22, 1.50) and 0.91 (95% CI 0.73, 1.13), respectively, compared with those without microvascular disease. CONCLUSIONS: Although microvascular disease, a non-traditional risk factor, was associated with incident arrhythmias in individuals with T2D, having optimal levels of risk factors may mitigate this risk.

Microvascular burden and long-term risk of stroke and dementia in type 2 diabetes mellitus.

OBJECTIVE: To examine the associations between microvascular disease (MVD) and risk of stroke, dementia, and their major subtypes among individuals with type 2 diabetes mellitus (T2DM). METHODS: We included 26,173 participants with T2DM from the UK Biobank who had no known stroke or dementia at baseline. MVD burden was reflected by the presence of retinopathy, peripheral neuropathy, and chronic kidney disease. Cox regression models were used to estimate hazard ratios (HRs) and 95 % confidential intervals (CIs) of stroke and dementia associated with overall MVD burden and individual MVD. RESULTS: During a median follow-up of 11.5 years, 1103 incident stroke (964 ischemic and 269 hemorrhagic stroke) and 813 incident dementia (312 Alzheimer's disease and 304 vascular dementia) cases were identified. The risk of stroke, dementia, and their major subtypes all increased with an increasing number of MVD (all P-trend <0.001). The adjusted HRs (95 % CIs) comparing three with no MVD were 5.03 (3.16, 8.02) for all stroke, 4.57 (2.75, 7.59) for ischemic stroke, and 6.60 (2.65, 16.43) for hemorrhagic stroke. The corresponding estimates were 4.28 (2.33, 7.86) for all-cause dementia, 6.96 (3.02, 16.01) for Alzheimer's disease, and 3.81 (1.40, 10.42) for vascular dementia. Among the three MVD, chronic kidney disease showed the strongest associations with both stroke subtypes, while peripheral neuropathy was most strongly associated with both dementia subtypes. CONCLUSIONS: Risk of stroke, dementia, and their major subtypes increased with an increasing number of MVD. The associations of individual MVD with stroke and dementia varied substantially by types of MVD.

Facile Reactive Oxygen Species-Scavenging Supramolecular Hydrogel to Promote Diabetic Wound Healing.

Chronic wound healing impairment is a significant complication in diabetes. Hydrogels that maintain wound moisture and enable sustained drug release have become prominent for enhancing chronic wound care. Particularly, hydrogels that respond to reactive oxygen species (ROS) are sought-after for their dual capacity to mitigate ROS and facilitate controlled drug delivery at the wound site. We have strategically designed an ROS-responsive and scavenging supramolecular hydrogel composed of the simple hexapeptide Glu-Phe-Met-Phe-Met-Glu (EFM). This hydrogelator, composed solely of canonical amino acids without additional ROS-sensitive motifs, forms a hydrogel rapidly upon sonication. Interaction with ROS leads to the oxidation of Met residues to methionine sulfoxide, triggering hydrogel disassembly and consequent payload release. Cellular assays have verified their biocompatibility and efficacy in promoting cell proliferation and migration. In vivo investigations underscore the potential of this straightforward hydrogel as an ROS-scavenger and drug delivery vehicle, enhancing wound healing in diabetic mice. The simplicity and effectiveness of this hydrogel suggest its broader biomedical applications in the future.

Microvascular Disease, Cardiovascular Health, and Risk of Coronary Heart Disease in Type 2 Diabetes: A UK Biobank Study.

CONTEXT: The interplay between cardiovascular health metrics (CVHMs) and microvascular disease (MVD) in relation to the risk of incident coronary heart disease (CHD) among individuals with type 2 diabetes mellitus (T2DM) remains to be evaluated. OBJECTIVE: To investigate the role of MVD and CVHMs in the development of CHD among T2DM. DESIGN: We included 19 664 participants with T2DM from the UK Biobank who had CVHM data and were free of CHD during recruitment. CVHMs were defined based on 5 behavioral (body mass index, diet, sleep duration, smoking, and regular exercise) and 3 biological (glycemic control, hyperlipidemia, and hypertension) factors. MVD was defined as the presence of retinopathy, peripheral neuropathy, or chronic kidney disease. Hazard ratio (HR) and 95% CI of CHD were estimated by multivariable Cox regression models. RESULTS: There were 3252 incident cases of CHD recorded after a median follow-up of 12.3 years. After multivariable adjustment, each MVD was separately associated with risk of CHD, and those who had 1 or ≥ 2 MVD had a 27% and an 87% increased risk of developing CHD, respectively. Each unfavorable CVHM was associated with a higher risk of CHD. As compared with MVD-free participants who had ideal CVHMs, those who had ≥ 2 MVD and had poor CVHMs were at particularly high risk of incident CHD (HR = 4.58; 95% CI: 3.58, 5.86), similarly when considering behavioral CVH or biological CVH separately. On an additive scale, there was a positive statistically significant interaction between number of MVD and CVHMs. CONCLUSION: Coexistence of multiple MVDs was associated with a substantially higher risk of CHD among individuals with T2DM. Such association may be amplified by unfavorable CVHMs.