AS03 adjuvant enhances the magnitude, persistence, and clonal breadth of memory B cell responses to a plant-based COVID-19 vaccine in humans.

Vaccine adjuvants increase the breadth of serum antibody responses, but whether this is due to the generation of antigen-specific B cell clones with distinct specificities or the maturation of memory B cell clones that produce broadly cross-reactive antibodies is unknown. Here, we longitudinally analyzed immune responses in healthy adults after two-dose vaccination with either a virus-like particle COVID-19 vaccine (CoVLP), CoVLP adjuvanted with AS03 (CoVLP+AS03), or a messenger RNA vaccination (mRNA-1273). CoVLP+AS03 enhanced the magnitude and durability of circulating antibodies and antigen-specific CD4+ T cell and memory B cell responses. Antigen-specific CD4+ T cells in the CoVLP+AS03 group at day 42 correlated with antigen-specific memory B cells at 6 months. CoVLP+AS03 induced memory B cell responses, which accumulated somatic hypermutations over 6 months, resulting in enhanced neutralization breadth of monoclonal antibodies. Furthermore, the fraction of broadly neutralizing antibodies encoded by memory B cells increased between day 42 and 6 months. These results indicate that AS03 enhances the antigenic breadth of B cell memory at the clonal level and induces progressive maturation of the B cell response.

Curcumin-loaded hydroxypropyl-ß-cyclodextrin inclusion complex with enhanced dissolution and oral bioavailability for epilepsy treatment.

Curcumin, the main bioactive component of turmeric, has a wild range of beneficial effects on central nervous diseases, including anti-Alzheimer's disease, antioxidant stress, and anti-inflammation. Currently, it has been demonstrated the anti-epileptic potential. However, curcumin has poor water solubility, high sensitivity to light and heat, and low absorption, which results in low bioavailability and greatly limits the clinical application of curcumin, as well as the elusive effects in anti-epileptic treatment.This study aimed to develop a curcumin hydroxypropyl-ß-cyclodextrin inclusion complex (CUR-HP-ß-CD) to improve its bioavailability and facilitate its potential development as an anti-epileptic drug. The CUR-HP-ß-CD was generated by the solvent evaporation method, which has efficient entrapment, high solubility, and facilitated bioavailability and brain distribution.The solubility of the CUR-HP-ß-CD was 63.5, 60.1, and 52.9 times that of the unformulated curcumin in H2O, HCl (pH 1.2), and PBS (pH 6.8), respectively. The bioavailability of CUR-HP-ß-CD is improved 2.8 times and 38.7 folds higher brain concentrations. Moreover, the therapeutic anti-epileptic effects of CUR-HP-ß-CD were much more effective in pentylenetetrazol (PTZ)-induced zebrafish and mouse models.This study showed a simple and reproducible strategy to effectively improve the bioavailability and therapeutic effects of curcumin, which could be potentially used in epilepsy treatment.

Comparative Effectiveness of Different Combinations of Treatment Interventions in Patients with Stroke at the Convalescence Stage Based on the Markov Decision Process.

OBJECTIVE: The objective of this study was to compare the effectiveness of different combinations of interventions in patients with stroke at the convalescence stage based on the electronic health records (EHRs) by using the Markov decision process (MDP) theory and explore the feasibility of the Markov model in the real-world study (RWS). METHODS: Screening was conducted for patients with stroke at the convalescence stage who were admitted to the Third Affiliated Hospital of Zhejiang Chinese Medical University from January 2012 to January 2017 based on the EHRs. The relevant clinical data were extracted, and the appropriate conversion was made (state-action-reward) according to the Markov model. The transformed data were analysed and solved by the MDP to obtain the best interventions for patients with various stroke recovery periods. RESULTS: 926 patients with stroke at the convalescence stage were initially selected. And according to the inclusion exclusion criteria, 854 patients were screened. Through the MDP, we obtained the following results: (1)when the patients with stroke at the convalescence stage have a medical history, but no complications, and mild neurological impairment, ≥66-year- and 18-45-year-old patients are advised to choose acupuncture treatment. 46-65-year-old patients are advised to choose rehabilitation treatment. When patients with moderate to severe neurological impairment, patients are advised to choose rehabilitation, Chinese herbal decoction, and acupuncture combined therapy. (2) Without complications or medical history, patients who are ≥ 66 years old are recommended to choose rehabilitation treatment when the nerve function impairment is mild; rehabilitation and acupuncture treatment are recommended when moderate and severe injuries are caused. (3) The combination of rehabilitation, Chinese herbal decoction, and acupuncture treatment is recommended for patients with phlegm and blood stasis. Acupuncture treatment is recommended for patients with mild impairment of nerve function in qi deficiency and blood stasis type. Rehabilitation, Chinese herbal decoction, and acupuncture treatment are recommended for moderate-severe injuries. CONCLUSIONS: The MDP makes it possible to study the effectiveness of various treatment methods in stroke patients who are at the convalescence stage. Further exploratory studies using MDP theory in other areas in which complex interventions are common would be worthwhile.