Proteomic signatures of type 2 diabetes predict the incidence of coronary heart disease.

Emerging evidence reveals a complex association between type 2 diabetes (T2D) and coronary heart disease (CHD), which share common risk factors and biological pathways. This study aims to identify the shared proteomic signatures of T2D and CHD, as well as whether the shared proteins predict incident CHD in T2D patients, and to develop predictive models. Utilizing data from 53,014 UK Biobank participants and 2923 plasma proteins, we identified 488 proteins associated with T2D, of which 125 proteins were also associated with CHD.

Fluorogenic Crystallization via Enzyme-Instructed Excited-State Intramolecular Proton Transfer for Dynamic Microenvironment Profiling.

Understanding dynamic changes within cellular microenvironments is crucial for elucidating biological processes and developing targeted therapies. Here, we present a rapid and straightforward strategy for profiling tumor microenvironments via fluorogenic crystallization driven by enzyme-instructed excited-state intramolecular proton transfer (ESIPT). By engineering ESIPT-based fluorophores, we achieve selective crystallization with strong dual-emission ratiometric fluorescence signals that are easily visualized, offering a real-time readout of tumor microenvironmental variations.

Topology-Oriented Lymph Node Drainage of Dendritic Polymer-TLR Agonist Conjugates to Enhance Vaccine Immunogenicity.

Strategically targeting lymph nodes (LNs) to orchestrate the initiation and regulation of adaptive immune responses is one of the most pressing challenges in the context of vaccination. Herein, a series of polymer-TLR agonist conjugates (PTACs) is developed to investigate the impact of dendritic-topological characteristics on their LN targeting activity in vivo, and their molecular weight (MW) on their pharmacokinetics in support of their LN homing. Notably, the dendritic 6-arm PTAC with a MW of 60 kDa (6A-PTAC-60k) rapidly delivered cargo to draining LNs after administration to peripheral tissues.

Tailoring the dendronized structures of cyclodextrin-based supramolecular nanoassemblies for enhanced tumor paraptosis via disrupting endoplasmic reticulum homeostasis.

Bioactive nanomaterials have been extensively utilized in medical applications. There are, however, very few reports on clinical applications of methylated β-cyclodextrin-derived supramolecular bioactive nanoagents, particularly in relation to the chemical features and biological properties. Herein, we designed and fabricated supramolecular bioactive nanoassemblies derived from permethyl β-cyclodextrin (PMCD) with increased proportions of PMCD on their dendronized side chains and further investigated the impact of chemical structures on their antitumor efficacy.

A sustained-release gel alleviates neuropathic pain in SNI mice by reversing Glu/GABA imbalance and chloride efflux disorders.

Impaired spinal GABAergic inhibitory neuronal system is one popular target for developing new drugs or procedures for treatment of neuropathic pain, but effective and transferable methods are still lacking. We designed an assembled, temperature sensitive and sustained releasing hydrogel to repair the impaired GABAergic neural system by reversing imbalance of glutamic acid (Glu) and γ-aminobutyric acid (GABA) and healing impaired Cl extrusion capacity of neurons. Hydrogel solution is a mixture of pluronic F-127, recombinant glutamate decarboxylase 67 (rGAD67) protein and CLP257, a K-Cl cotransporter isoform 2 (KCC2) enhancer.

Accelerometer-derived movement behaviours and risk of mortality among individuals with pre-existing depression: prospective cohort study.

Background: Evidence is largely limited regarding the extent to which abnormal behavioural profiles, including physical inactivity, sedentary behaviour and inadequate sleep duration, impact long-term health conditions in individuals with pre-existing depression.

Aims: To investigate the associations between accelerometer-derived daily movement behaviours and mortality in individuals with pre-existing depression.

Method: Between 2013 and 2015, a total of 10 914 individuals with pre-existing depression were identified from the UK Biobank through multiple sources including self-reported symptoms, records of antidepressant usage and diagnostic recording based on the 10th Revision of the International Classification of Diseases (ICD-10) codes F32-F33.

Multifunctional hydrogel electronics for closed-loop antiepileptic treatment.

Closed-loop strategies offer advanced therapeutic potential through intelligent disease management. Here, we develop a hydrogel-based, single-component, organic electronic device for closed-loop neurotherapy. Fabricated out of conductive hydrogels, the device consists of a flexible array of microneedle electrodes, each of which can be individually addressed to perform electrical recording and control chemical release with sophisticated spatiotemporal control, thus pioneering a smart antiseizure therapeutic system by combining electrical and pharmacological interventions.

Electrically-driven drug delivery into deep cutaneous tissue by conductive microneedles for fungal infection eradication and protective immunity.

Fungal infections affect over 13 million people worldwide and are responsible for 1.5 million deaths annually. Some deep cutaneous fungal infections may extend the dermal barriers to cause systemic infection, resulting in substantial morbidity and mortality.

Harnessing exosomes for targeted therapy: strategy and application.

Exosomes, nanoscopic extracellular vesicles produced by cells, are pivotal in mediating intracellular communication by transporting nucleic acids, proteins, lipids, and other bioactive molecules, thereby influencing physiological and pathological states. Their endogenous origin and inherent diversity confer distinct advantages over synthetic vehicles like liposomes and nanoparticles in diagnostic and therapeutic applications. Despite their potential, the clinical utility of exosomes is hampered by challenges such as limited storage stability, yield, purity, and targeting efficiency.

Enhanced angiogenesis in porous poly(ε-caprolactone) scaffolds fortified with methacrylated hyaluronic acid hydrogel after subcutaneous transplantation.

A composite scaffold composed of a porous scaffold and hydrogel filling can facilitate engraftment, survival, and retention in cell transplantation processes. This study presents a composite scaffold made of poly(ε-caprolactone) (PCL) and methacrylated hyaluronic acid (MeHA) hydrogel and describes the corresponding physical properties (surface area, porosity, and mechanical strength) and host response (angiogenesis and fibrosis) after subcutaneous transplantation. Specifically, we synthesise MeHA with different degrees of substitution and fabricate a PCL scaffold with different porosities.

Accelerometer-derived 'weekend warrior' physical activity pattern and brain health.

Extensive evidence shows the beneficial effect of adhering to a regular physical activity (PA) pattern on brain health. However, whether the 'weekend warrior' pattern, characterized by concentrated moderate-to-vigorous PA (MVPA) over 1-2 days, is associated with brain health is unclear. Here, we perform a prospective cohort study including 75,629 participants from the UK Biobank with validated accelerometry data.

Association of accelerometer-derived physical activity with all-cause and cause-specific mortality among individuals with cardiovascular diseases: a prospective cohort study.

Aims: To investigate the association of accelerometer-measured intensity-specific physical activity (PA) with all-cause and cause-specific mortality among individuals with cardiovascular disease (CVD).

Methods And Results: In this prospective cohort study, 8024 individuals with pre-existing CVD (mean age: 66.6 years, female: 34.

Associations between device-measured and self-reported physical activity and common mental disorders: Findings from a large-scale prospective cohort study.

Objectives: To investigate the associations between device-measured and self-reported physical activity (PA) and incident common mental disorders in the general population.

Design And Setting: Large-scale prospective cohort study.

Participants: Using the UK Biobank data, a validated PA questionnaire was used to estimate self-reported weekly PA in 365 656 participants between 2006 and 2010 while 91 800 participants wore wrist-worn accelerometers for 7 days in 2013-2015 to derive objectively measured PA.

Baroreceptor-Inspired Microneedle Skin Patch for Pressure-Controlled Drug Release.

: We have developed a baroreceptor-inspired microneedle skin patch for pressure-controlled drug release. : This design is inspired by the skin baroreceptors, which are mechanosensitive elements of the peripheral nervous system. We adopt the finger touching to trigger the electric stimulation, ensuring a fast-response and user-friendly administration with potentially minimal off-target effects.

Accelerometer-derived physical activity and mortality in individuals with type 2 diabetes.

Physical activity (PA) has been shown to reduce diabetes mortality, but largely based on imprecise self-reported data, which may hinder the development of related recommendations. Here, we perform a prospective cohort study of 19,624 individuals with type 2 diabetes (T2D) from the UK Biobank with a median follow-up of 6.9 years.

Trajectories of depressive symptoms and risk of cardiovascular disease, cancer and mortality: a prospective cohort study.

Background: Depressive symptoms are established risk factors for various health outcomes. However, previous studies assessed depressive symptoms at a single time point, neglecting individual variations over time.

Aims: To identify depressive symptoms trajectories through repeated measures and examine their associations with cardiovascular disease (CVD), cancer and mortality.

Association of social health with all-cause mortality and cause-specific mortality: A population-based cohort study.

Background: Previous studies only focused on the individual social factors, without considering the overall social health patterns. The present study aimed to develop an integrated social health score (SHS) and investigate its associations with all-cause, cardiovascular disease (CVD), cancer mortality.

Methods: A total of 330,716 participants (mean age 56.

Associations between Recreational Screen Time and Brain Health in Middle-Aged and Older Adults: A Large Prospective Cohort Study.

Objectives: To investigate the associations of recreational screen time with risks of brain-related disorders (dementia, stroke, and Parkinson's disease) and neuroimaging features.

Design: Prospective cohort study.

Setting And Participants: A total of 407,792 participants from the UK Biobank who were free of dementia, stroke, or Parkinson's disease at enrollment (2006-2010).

Healthy lifestyle and the risk of depression recurrence requiring hospitalisation and mortality among adults with pre-existing depression: a prospective cohort study.

Background: Although lifestyle-based treatment approaches are recommended as important aspects of depression care, the quantitative influence of aggregated healthy lifestyles on depression recurrence and mortality remains unknown.

Objective: To investigate the association between healthy lifestyle and the risks of first-time hospitalisation for recurrent depression and mortality.

Methods: 26 164 adults with depression (mean (SD) age, 56.

Physical Activity, Mental Activity, and Risk of Incident Stroke: A Prospective Cohort Study.

Background: Cumulative evidence suggests a correlation between physical or mental activity and the risk of stroke. However, the combined impact of these activities on stroke onset remains unexplored. This study identified physical and mental activity patterns using principal component analysis and investigated their associations with risk of incident stroke in the general population.

Translation and Validation of the Chinese Language Version of the Control of Allergic Rhinitis and Asthma Test in Patients with Allergic Rhinitis.

Objective: Due to the escalating global prevalence of allergic rhinitis (AR) and its status as an independent risk factor for asthma, timely and effective control of AR is crucial. Achieving this often involves the accurate assessment of AR. Currently, the Control of Allergic Rhinitis and Asthma Test (CARAT) is widely used as an assessment tool, but its measurement effectiveness in Chinese AR patients remains unclear.

Topical Delivery of microRNA-125b by Framework Nucleic Acids for Psoriasis Treatment.

Purpose: Psoriasis is a chronic and recurrent inflammatory dermatitis characterized by T cell imbalance and abnormal keratinocyte proliferation. MicroRNAs (miRNAs) hold promise as therapeutic agents for this disease; however, their clinical application is hindered by poor stability and limited skin penetration. This study demonstrates the utilization of Framework Nucleic Acid (FNA) for the topical delivery of miRNAs in psoriasis treatment.

Immune-mediated diseases are associated with a higher risk of ALS incidence: a prospective cohort study from the UK Biobank.

Objective: The occurrence of immune-mediated diseases (IMDs) in amyotrophic lateral sclerosis (ALS) patients is widely reported. However, whether IMDs and ALS is a simple coexistence or if there exists causal relationships between the two has been a subject of great interest to researchers.

Methods: A total of 454,444 participants from the prospective cohort of UK Biobank were recruited to investigate the longitudinal association between IMDs and ALS.