Effects of folic acid supplementation on cognitive impairment: A meta-analysis of randomized controlled trials.

OBJECTIVE: With the increasing number of patients with cognitive impairment, nonpharmacological ways to delay cognitive impairment have attracted people's attention, such as lifestyle changes and nutritional supplementation. Folic acid supplementation appears to be a promising treatment option. However, it remains controversial whether folic acid supplementation is effective in delaying adult's cognitive impairment. Therefore, we conducted a meta-analysis to analyze the effects of folic acid supplementation on different cognitive impairments. METHODS: We systematically searched PubMed, Web of Science, EMbase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), WanFang and VIP databases for randomized controlled trials on January 22, 2024. The included population comprised those diagnosed with cognitive impairment. We included trials that compared folic acid treatment with placebo, other dosing regimens, or other intervention controls. Conducting quality evaluation of included studies according to the Cochrane Risk of Bias tool. Statistical analyses were performed using Review Manager software. RESULTS: Twenty-two trials, including 3604 participants, met inclusion criteria. Compared with controls, the cognitive function of Alzheimer's disease (AD) patients showed improvement with folic acid supplementation: supplementation with < 3 mg (standardized mean differences (SMD) = 0.15, 95% confidence interval (CI) -0.10 to 0.41), and supplementing with ≥ 3 mg folic acid could improve cognitive function in AD patients (SMD = 1.03, 95% CI 0.18 to 1.88). Additionally, it reduced homocysteine (HCY) levels (mean differences (MD) = -4.74, 95% CI -8.08 to -1.39). In mild cognitive impairment (MCI) patients, cognitive function improved with folic acid supplementation: supplementation with > 400 µg (SMD = 0.38, 95% CI 0.13 to 0.63), and supplementation with ≤ 400 µg (SMD = 1.10, 95% CI 0.88 to 1.31). It also reduced HCY levels at intervention ≤ 6 months (MD = -3.93, 95% CI -5.05 to -2.82) and intervention > 6 months (MD = -4.38, 95% CI -5.15 to -3.61). However, supplementing with folic acid did not improve cognitive function in vascular cognitive impairment (VCI) patients, with folic acid supplements < 3 mg (SMD = -0.07, 95% CI -0.23 to -0.08), folic acid supplements ≥ 3 mg (SMD = 0.46, 95% CI -0.57 to 1.49), however, it reduced HCY levels at intervention > 6 months (MD = -5.91, 95% CI -7.13 to -4.69) and intervention ≤ 6 months (MD = -11.15, 95% CI -12.35 to -9.95). CONCLUSIONS: Supplement folic acid is beneficial to the cognitive profile of patients with MCI, supplementation with ≥ 3 mg folic acid can improve cognitive function in AD patients.

Nickel-Catalyzed Cross-Electrophile Coupling of 1,2,3-Benzotriazin-4(3H)-ones with Aryl Bromides.

The nickel-catalyzed cross-electrophile coupling of 1,2,3-benzotriazin-4(3H)-ones with aryl bromides to generate a diverse array of ortho-arylated benzamide derivatives has been developed. The reaction displayed good functional group tolerance with Zn as the reductant. The key to this transformation is the ring opening of benzotriazinones, which undergo a denitrogenative process to obtain various benzamide derivatives (29 examples, 42-93% yield). The scalability of this transformation was demonstrated.

In Situ Fluorescence Probing of the Formation of Calcium Phosphate Prenucleation Clusters.

Initial-stage prenucleation clusters (PNCs) are critical in calcium phosphate (CaP) biomineralization and thus the formation mechanisms of human bones and teeth. However, several features of PNCs require further examination, e.g., structure, ionic stoichiometry, kinetics, thermodynamics, and nucleation mechanism. In this study, we used poly(acrylic acid) (PAA)-Ca(Eu) complexes with partial Eu3+ substitution as pre-PNCs and established a fluorescence method to study PNC formation in situ based on Eu-O charge-transfer transitions. The kinetics and thermodynamics of PNC formation were explored by probing the fluorescence changes of Eu-O charge-transfer transitions during bonding between the pre-PNCs and PO43-. PNC formation was consistent with the pseudo-second-order kinetic and Langmuir isothermal adsorption models. The flexible structures of PNCs aided in regulating the subsequent nucleation and crystallization. This study provides an in situ fluorescence probing method with critical guiding significance in addressing the features of PNC formation, in addition to biomineralization.

Characterization of plasma protein binding dissociation with online SPE-HPLC.

A novel parameter of relative recovery (R re) was defined and determined by online SPE-HPLC to characterize plasma protein binding (PPB) kinetics of highly plasma binding drugs. The proportional relationship of R re with k off of PPB has been established with a new SPE model. A rapid, easy to use method could potentially be used to categorize PK properties of the drug candidates in the decision process of drug discovery and development.