Among hypertensive cohorts across different nations, the relationship between the triglyceride-glucose index (TyG) and its conjunction with obesity metrics in relation to cardiovascular disease (CVD) incidence and mortality remains to be elucidated. This study enrolled 9,283, 164,357, and 5,334 hypertensives from the National Health and Nutrition Examination Survey (NHANES), UK Biobank (UKBB), and Shanghai Pudong cohort. The related outcomes for CVD were defined by multivariate Cox proportional hazards models, Generalized Additive Models and Mendelian randomization analysis. Mediation analysis explored the mediating role of inflammatory markers in the above relationships. Five measures of insulin resistance were linked to CVD and related death in a U-shaped pattern, with the highest group having different risk increases. Higher glucose triglyceride-waist height ratio (TyG-WHTR) was linked to higher all-cause mortality (UKBB: HR 1.21, 95%CI 1.16–1.26, NHANES: HR 1.17, 95%CI 1.00–1.36), CVD mortality (UKBB: HR 1.36, 95%CI 1.23–1.49, NHANES: HR 1.32, 95%CI 1.00–1.72) risks. In the China Pudong cohort, higher triglyceride/high-density lipoprotein-cholesterol (TG/HDL_C) ratio was associated with higher risks of CVD and stroke (HR 1.31, 95%CI 1.00–1.73 and 1.67, 1.06–2.63). Inflammation markers like systemic inflammatory response index (SIRI) and C-reactive protein (CRP) partially explained these links, with CRP having a stronger effect. Genetically predicted TyG was also linked to stroke (OR 1.26, 95%CI 1.10–1.45) risk. An elevated TyG index and its related indices are significantly correlated with an increased risk of CVD and related mortality across three national cohorts. These indices are anticipated to serve as valid predictors of incident CVD and mortality in individuals with hypertension.

Skin scarring devoid of dermal appendages after severe trauma has unfavorable effects on aesthetic and physiological functions. Here we present a method for large-area wound regeneration using biodegradable aligned extracellular matrix scaffolds. We show that the implantation of these scaffolds accelerates wound coverage and enhances hair follicle neogenesis. We perform multimodal analysis, in combination with single-cell RNA sequencing and spatial transcriptomics, to explore the immune responses around biomaterials, highlighting the potential role of regulatory T cells in mitigating tissue fibrous by suppressing excessive type 2 inflammation. We find that immunodeficient mice lacking mature T lymphocytes show the typical characteristic of tissue fibrous driven by type 2 macrophage inflammation, validating the potential therapeutic effect of the adaptive immune system activated by biomaterials. These findings contribute to our understanding of the coordination of immune systems in wound regeneration and facilitate the design of immunoregulatory biomaterials in the future.

Macrophages play a vital role in cardiac repair following myocardial infarction (MI). An enriched environment (EE) is involved in the regulation of macrophage-related activities and disease progression; however, whether EE affects the phenotype and function of macrophages to improve postinfarction cardiac repair remains unknown. In this study, we found that EE improved cardiac function, decreased mortality, and ameliorated adverse ventricular remodeling in mice after MI, with these outcomes closely related to the increased survival of Ly6C ^low macrophages and their CCR2 ⁻ MHCII ^low subsets. EE increased the expression of brain-derived neurotrophic factor (BDNF) in the hypothalamus, leading to higher circulating levels of BDNF, which, in turn, regulated the cardiac macrophages. BDNF bound to tropomyosin receptor kinase B to activate downstream ERK1/2 and AKT pathways, promoting macrophage survival. These findings demonstrate that EE optimizes postinfarction cardiac repair and highlights the significance of EE as a previously unidentified strategy for impeding adverse ventricular remodeling.

Biomaterials are one of efficient treatment options for tissue defects in regenerative medicine. Compared to synthetic materials which tend to induce chronic inflammatory response and fibrous capsule, extracellular matrix (ECM) scaffold materials composed of biopolymers are thought to be capable of inducing a pro-regenerative immune microenvironment and facilitate wound healing. Immune cells are the first line of response to implanted biomaterials. In particular, macrophages greatly affect cell behavior and the ultimate treatment outcome based on multiple cell phenotypes with various functions. The macrophage polarization status is considered as a general reflection of the characteristics of the immune microenvironment. Since numerous reports has emphasized the limitation of classical M1/M2 nomenclature, high-resolution techniques such as single-cell sequencing has been applied to recognize distinct macrophage phenotypes involved in host responses to biomaterials. After reviewing latest literatures that explored the immune microenvironment mediated by ECM scaffolds, this paper describe the behaviors of highly heterogeneous and plastic macrophages subpopulations which affect the tissue regeneration. The mechanisms by which ECM scaffolds interact with macrophages are also discussed from the perspectives of the ECM ultrastructure along with the nucleic acid, protein, and proteoglycan compositions, in order to provide targets for potential therapeutic modulation in regenerative medicine.

Background: This study is designed to explore the correlation between multiple healthy lifestyles within the framework of “lifestyle medicine”, and the mortality risk of nonalcoholic fatty liver disease (NAFLD). Methods: The National Health and Nutrition Examination Survey (NHANES) database was employed. The analysis consisted of 5542 participants with baseline NAFLD and 5542 matched non-NAFLD participants from the database. Lifestyle information, including five low risk factors advocated by lifestyle medicine (healthy diet, vigorous physical activity, healthy sleep duration, avoiding smoking, and maintaining a non-depressed psychological status), was collected through a baseline questionnaire. Cox proportional hazards regression models and Kaplan–Meier survival curve were used to evaluate risk of mortality. In addition, subgroups were analyzed according to gender, age, body mass index and waist circumference. Results: In total, 502 deaths (n = 181 deaths from cardiovascular disease (CVD)) were recorded among NAFLD participants after the median follow up duration of 6.5 years. In the multivariate-adjusted model, compared to participants with an unfavorable lifestyle (scoring 0–1), NAFLD participants with a favorable lifestyle (scoring 4–5) experienced a 56% reduction in all-cause mortality and a 66% reduction in CVD mortality. Maintaining an undepressed psychological state and adhering to vigorous exercise significantly reduced CVD mortality risk in NAFLD participants (HR, 0.64 [95% CI, 0.43–0.95]; HR, 0.54 [95% CI, 0.33–0.88]) while maintaining healthy sleep reduced premature mortality due to CVD by 31%. Conclusions: Healthy lifestyle, characterized by maintaining an undepressed mental state and healthy sleep, significantly mitigates the risk of all-cause, CVD, and premature mortality risk among NAFLD patients, with a particularly pronounced effect observed in female and obese subpopulations.

The usage of bone substitute granule materials has improved the clinical results of alveolar bone deficiencies treatment and thus broadened applications in implant dentistry. However, because of the complicated mechanisms controlling the foreign body response, no perfect solution can avoid the fibrotic encapsulation of materials till now, which may impair the results of bone regeneration, even cause the implant materials rejection. Recently, the concept of ‘osteoimmunology’ has been stressed. The outcomes of bone regeneration are proved to be related to the bio-physicochemical properties of biomaterials, which allow them to regulate the biological behaviours of both innate and adaptive immune cells. With the development of single cell transcriptome, the truly heterogeneity of osteo-immune cells has been clarifying, which is helpful to overcome the limitations of traditional M1/M2 macrophage nomenclature and drive the advancements of particulate biomaterials applications. This review aims at introducing the mechanisms of optimal osseointegration regulated by immune systems and provides feasible strategies for the design of next generation ‘osteoimmune-smart’ particulate bone substitute materials in dental clinic.