Associations between cardiometabolic multimorbidity and cerebrospinal fluid biomarkers of Alzheimer's disease pathology in cognitively intact adults: the CABLE study.

BACKGROUND: Cardiometabolic multimorbidity is associated with an increased risk of dementia, but the pathogenic mechanisms linking them remain largely undefined. We aimed to assess the associations of cardiometabolic multimorbidity with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) pathology to enhance our understanding of the underlying mechanisms linking cardiometabolic multimorbidity and AD. METHODS: This study included 1464 cognitively intact participants from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) database. Cardiometabolic diseases (CMD) are a group of interrelated disorders such as hypertension, diabetes, heart diseases (HD), and stroke. Based on the CMD status, participants were categorized as CMD-free, single CMD, or CMD multimorbidity. CMD multimorbidity is defined as the coexistence of two or more CMDs. The associations of cardiometabolic multimorbidity and CSF biomarkers were examined using multivariable linear regression models with demographic characteristics, the APOE ε4 allele, and lifestyle factors as covariates. Subgroup analyses stratified by age, sex, and APOE ε4 status were also performed. RESULTS: A total of 1464 individuals (mean age, 61.80 years; age range, 40-89 years) were included. The markers of phosphorylated tau-related processes (CSF P-tau181: ß = 0.165, P = 0.037) and neuronal injury (CSF T-tau: ß = 0.065, P = 0.033) were significantly increased in subjects with CMD multimorbidity (versus CMD-free), but not in those with single CMD. The association between CMD multimorbidity with CSF T-tau levels remained significant after controlling for Aß42 levels. Additionally, significantly elevated tau-related biomarkers were observed in patients with specific CMD combinations (i.e., hypertension and diabetes, hypertension and HD), especially in long disease courses. CONCLUSIONS: The presence of cardiometabolic multimorbidity was associated with tau phosphorylation and neuronal injury in cognitively normal populations. CMD multimorbidity might be a potential independent target to alleviate tau-related pathologies that can cause cognitive impairment.

NIR-Cleavable and pH-Responsive Polymeric Yolk-Shell Nanoparticles for Controlled Drug Release.

Responsive drug release and low toxicity of drug carriers are important for designing controlled release systems. Here, a double functional diffractive o-nitrobenzyl, containing multiple electron-donating groups as a crosslinker and methacrylic acid (MAA) as a monomer, was used to decorate upconversion nanoparticles (UCNPs) to produce robust poly o-nitrobenzyl@UCNP nanocapsules using the distillation-precipitation polymerization and templating method. Poly o-nitrobenzyl@UCNP nanocapsules with a robust yolk-shell structure exhibited near-infrared (NIR) light-/pH-responsive properties. When the nanocapsules were exposed to 980 nm NIR irradiation, the loaded drug was efficiently released by altering the shell of the nanocapsules. The photodegradation kinetics of the poly o-nitrobenzyl@UCNP nanocapsules were studied. The anticancer drug, doxorubicin hydrochloride (DOX), was loaded at pH 8.0 with a loading efficiency of 13.2 wt %. The Baker-Lonsdale model was used to determine the diffusion coefficients under different release conditions to facilitate the design of dual-responsive drug release devices or systems. Additionally, cytotoxicity studies showed that the drug release of DOX could be efficiently triggered by NIR to kill cancer cells in a controlled manner.

Integrated Functional High-Strength Hydrogels with Metal-Coordination Complexes and H-Bonding Dual Physically Cross-linked Networks.

With the deepening of research on high-strength hydrogels, the multi-functional study of hydrogels has become a hot spot. In this paper, a dual cross-linked physical high-strength hydrogels is prepared by a relatively simple method. 2-Vinyl- 4,6-Diamino-2-vinyl-1,3,5-triazine (VDT) induces the formation of the first cross-linking points through the interaction of hydrogen bonds with poly(acrylamide-co-acrylic acid) (PAm-co-Ac) chains, then the secondary physical cross-linkers Fe3+ that introduce ionic coordinates between Fe3+ and -COO- groups. Due to the synergistic effect of hydrogen bonding and ionic coordination, hydrogels possess high tensile strength (approx. 4.34 MPa), large elongation (approx. 17.64 times), and good healing properties under alkali solution after cutting into two pieces. Meanwhile, VDT contains diaminotriazine functional groups that easily form hydrogen bonds so that the polymer of hydrogels could absorb 5-fluorouridine. In addition, the contribution of ionic polymer segments enables pH to be sensitive to hydrogels and facilitates the adsorption of a large number of ionic monomers to form ionic conductive networks, the prepared hydrogel capacitor device has very high sensitivity to pressure and deformation, and can detect the movement behavior of the human body. The dual-physical cross-linked hydrogels had a selective adsorption to biological small molecules and could be assembled into a flexible wearable device with high sensitivity.

Dual Ionically Cross-linked Double-Network Hydrogels with High Strength, Toughness, Swelling Resistance, and Improved 3D Printing Processability.

We report a dual ionic cross-linking approach for the preparation of double-network hydrogels with robustness, high strength, and toughness, sodium alginate/poly(acrylamide- co-acrylic acid)/Fe3+ (SA/P(AAm- co-AAc)/Fe3+), in a facile "one-step" dual ionic cross-linking method. We take advantage of the abundant carboxyl groups on alginate molecules and the copolymer chains and their high coordination capacity with multivalent metal ions to obtain hydrogels with high strength and toughness. The optimal SA/P(AAm- co-AAc)/Fe3+ (SA 2 wt % and AAc 5 mol %) hydrogels showed a remarkable mechanical performance with 3.24 MPa tensile strength and 1228% strain, both of which remained stable with 76% water content and were highly swelling resistant in an aqueous environment. The hydrogels possessed high fatigue resistance, self-recovery, pH-triggered healing capability, shape memory, and reversible gel-sol transition facilitated by pH regulation. Moreover, they show three-dimensional (3D) printing processability by properly adjusting the solution viscosity. The approach may provide a convenient way of obtaining hydrogels having high strength and toughness with a number of desirable properties for a broad range of biomedical applications.

Photoreductive synthesis of water-soluble fluorescent metal nanoclusters.

Water-soluble fluorescent copper, silver and gold nanoclusters with quantum yields of 2.2, 6.8 and 5.3%, respectively, are prepared by a robust photoreduction of their inorganic precursors in the presence of poly (methacrylic acid) functionalized with pentaerythritol tetrakis 3-mercaptopropionate.