Overcoming apoptosis resistance is necessary to ensure an effective cancer treatment; however, it is currently very difficult to achieve. A desirable alternative for cancer treatment is the targeted activation of pyroptosis, a unique type of programmed cell death. However, the pyroptosis inducers that are efficient for cancer therapy are limited. This work reports the engineering of 2D NiCoO_x nanosheets as inducers of the production of harmful reactive oxygen species (ROS), which promote intense cell pyroptosis, and that can be applied to ultrasound (US)‐augmented catalytic tumor nanotherapy. The main therapeutic task is carried out by the 2D NiCoO_x nanosheets, which have four multienzyme‐mimicking activities: peroxidase‐ (POD), oxidase‐ (OXD), glutathione peroxidase‐ (GPx), and catalase‐ (CAT) mimicking activities. These activities induce the reversal of the hypoxic microenvironment, endogenous glutathione depletion, and a continuous ROS output. The ROS‐induced pyroptosis process is carried out via the ROS‐NLRP3‐GSDMD pathway, and the exogenous US activation boosts the multienzyme‐mimicking activities and favors the incremental ROS generation, thus inducing mitochondrial dysfunction. The anti‐cancer experimental results support the dominance of NiCoO_x nanosheet‐induced pyroptosis. This work expands on the biomedical applications of engineering 2D materials for US‐augmented catalytic breast cancer nanotherapy and deepens the understanding of the multienzyme activities of nanomaterials.

Senescent-endothelial cells significantly accelerate atherosclerosis progression, making the mitigation of cellular aging a promising strategy for treating the disease. Nitric oxide (NO), a low molecular weight and lipophilic gas, has been shown to penetrate cell membranes effectively and delay cell senescence. In this study, we designed and engineered osteopontin (OPN)-modified nanoliposomes (CZALO) that encapsulate L-arginine (L-Arg) and cerium-zirconium oxide nanoparticles (CZ NPs), which exhibit enzyme-like activities for targeted atherosclerosis treatment. Following inflammatory chemotaxis and OPN-mediated internalization by macrophages, CZ NPs released from CZALO nanoliposomes significantly scavenge reactive oxygen species, thereby inhibiting cholesterol uptake and promoting macrophage phenotypic transformation, resulting in both antioxidant and anti-inflammatory effects. Additionally, nitric oxide synthase (NOS) overexpressed in macrophages catalyzes L-Arg to produce NO, which is then selectively released in situ and diffuses into endothelial cells, exerting anti-aging effects by regulating senescence-associated secretory phenotype factor secretion, enhancing lysosomal function, alleviating cell cycle arrest, and reducing DNA damage. The antioxidant and anti-aging effects of CZALO nanoliposomes collectively alleviate atherosclerotic burden with minimal toxicity both in vitro and in vivo. This “two-birds-one-stone” nanotherapeutic offers a novel approach for regulating vascular microenvironment homeostasis and improving therapeutic efficiency in atherosclerosis treatment.

Previous observational studies have highlighted potential links between the consumption of processed meat and red meat (such as pork, mutton, and beef intake) and the occurrence of mental disorders. However, it is unclear whether a causal association exists. Therefore, we employed the Mendelian randomization (MR) study to investigate the causal effects of genetically predicted processed meat and red meat on mood disorders (MD), anxiety disorders (AD), and major depressive disorder (MDD). Genetic instruments for processed and red meat were selected from the Genome-Wide Association Study (GWAS) of the UK Biobank Study. Their associations with MD (42,746 cases 254,976), AD (35,385 cases and 254,976 controls), and MDD (38,225 cases and 299,886 controls) were obtained from the FinnGen Consortium. The inverse variance weighted (IVW) method was the primary method for two-sample MR analysis. Additionally, we employed complementary analysis to assess the robustness of our MR findings (eg, MR Egger and weighted median). We also conducted multiple sensitivity analyses to investigate horizontal pleiotropy and heterogeneity. Moreover, we performed a univariate and multivariable MR (MVMR) study to evaluate these associations. In our univariate MR analysis, we observed that genetically predicted beef intake was associated with a reduced risk of MD [odds ratio (OR) = 0.403, 95 % confidence interval (CI) = 0.246-0.659; P_IVW = 4.428 × 10^-5], AD (OR = 0.443, 95 % CI = 0.267-0.734; P_IVW = 1.563 × 10^-3), and MDD (OR = 0.373, 95 % CI = 0.216-0.643; P_IVW = 3.878 × 10^-4). After adjusting for processed meat, pork, and mutton intake in the MVMR analysis, the protective association of beef intake against MD and MDD remained. However, there was no substantial evidence indicating a significant causal relationship between processed meat, pork, and mutton intake and the occurrence of mental disorders. Furthermore, our sensitivity analysis revealed no significant evidence of horizontal pleiotropy. These findings support a causal relationship between genetically predicted beef intake and reducing the risk of MD and MDD.

Purpose: This study aimed to assess the knowledge, attitudes and practices (KAP) among middle-aged and elderly population towards ultrasound screening for strokes. Patients and Methods: This web-based cross-sectional study was conducted between March, 2023, and May, 2023 at Shanghai Eighth People’s Hospital. A self-designed questionnaire was developed to collect demographic information of middle-aged and elderly population and assess their knowledge, attitudes and practices toward ultrasound screening for strokes. Results: A total of 552 participants enrolled in this study, among them 151 (27.36%) aged above 60 years old, 306 (55.43%) resided in rural area, 239 (43.30%) possessed educational attainment at the level of junior college, college or above. The mean knowledge, attitudes and practice scores were 5.53 ± 2.56, 40.22 ± 5.60 and 38.30 ± 7.38, respectively. Pearson’s analysis was performed to assess the relationship between knowledge, attitudes, and practices. It was shown that knowledge and attitudes were positively correlated (r = 0.544, P < 0.001), and knowledge and practices were also positively correlated (r = 0.404, P < 0.001). Additionally, there was a positive correlation between attitude and practice scores (r = 0.566, P < 0.001). Conclusion: The results of this study demonstrate that the middle-aged and elderly population exhibited insufficient knowledge, positive attitudes, and moderate practices towards ultrasound screening for strokes. There is a need to improve the understanding of stroke risk factors, symptoms, and emergency measures among this population.

Previous observational studies have explored the association between serum lipids, apolipoproteins, and adverse ventricular/aortic structure and function. However, whether a causal link exists is uncertain. This study employed a two-sample Mendelian randomization (MR), colocalization, reverse, and multivariable MR (MVMR) approach to examine the causal associations among five serum lipids, two apolipoproteins, and 32 cardiac magnetic resonance (CMR) traits. Utilizing single-nucleotide polymorphisms (SNPs) linked to serum lipids and apolipoproteins as instrumental variables. CMR traits from seven independent genome-wide association studies served as preclinical endophenotypes, offering insights into aortic and cardiac structure/function. The primary analysis utilized a random-effects inverse variance method (IVW), followed by sensitivity and validation analyses. In the primary IVW MR analyses, genetically predicted low-density lipoprotein cholesterol (LDL-C) levels were positively correlated with increased descending aorta strain (DAo strain) (β = 0.098; P = 2.69E-07) and ascending aorta strain (AAo strain) (β = 0.079; P = 5.19E-05). Genetically predicted high-density lipoprotein cholesterol (HDL-C) levels were positively correlated with left ventricular radial peak diastolic strain rate (LV-PDSRll) (β = 0.176; P = 2.89E-05) and the left ventricular longitudinal peak diastolic strain rate (LV-PDSRrr) (β = 0.059; P = 2.44E-06), and negatively correlated with left ventricular regional wall thickness (LVRWT). While apolipoprotein B (ApoB) levels were positively correlated with AAo strain (β = 0.076; P = 1.16E-05), DAo strain (β = 0.065; P = 2.77E-05). A shared causal variant was identified to demonstrate the associations of ApoB with AAo strain and DAo strain using colocalization analysis. Sensitivity analyses confirmed the robustness of these associations. Targeting lipid and apolipoprotein levels through interventions may provide novel strategies for the primary prevention of CVDs.