Red cell membrane-coating Prussian blue for combined photothermal and NO gas therapy for nasopharyngeal carcinoma.

Nitric oxide (NO) gas molecules have demonstrated remarkable anti-tumor effects and minimal susceptibility to drug resistance, establishing as a promising modality for effective tumor treatment. However, how to realize its stable and efficient delivery in vivo is still a challenge. In this study, we have developed a heat-responsive biomimetic nano erythrocyte (M/B@R) by loading a NO donor (BNN6) onto mesoporous Prussian blue (M-PB) and subsequently enveloping them with red blood cell membranes. The preserved integrity of the red blood cell membrane (RBCm) structure could ensure its excellent biosafety, prolong its circulation time within the bloodstream and then enhance the accumulation of BNN6 at tumor sites. When M/B@R is stimulated by near-infrared light (NIR-II, 808 nm) irradiation, the nanoparticle could generate significant heat for photothermal therapy (PTT) by the characteristic NIR absorption of M-PB and then NO could also be efficiently released. The generated NO further facilitates the formation of ONOO-, a highly toxic species to tumors, while also alleviating tumor hypoxia. Remarkably, M/B@R, with NIR as the excitation source, induces combined lethality through hyperthermia, DNA damage, and tumor hypoxia relief. This novel combination strategy provides a new avenue for PTT/NO-induced cancer therapy.

pH-Sensitive and Biodegradable Mn3(PO4)2·3H2O Nanoparticles as an Adjuvant of Protein-Based Bivalent COVID-19 Vaccine to Induce Potent and Broad-Spectrum Immunity.

Developing a novel and potent adjuvant with great biocompatibility for immune response augmentation is of great significance to enhance vaccine efficacy. In this work, we prepared a long-term stable, pH-sensitive, and biodegradable Mn3(PO4)2·3H2O nanoparticle (nano-MnP) by simply mixing MnCl2/NaH2PO4/Na2HPO4 solution for the first time and employed it as an immune stimulant in the bivalent COVID-19 protein vaccine comprised of wild-type S1 (S1-WT) and Omicron S1 (S1-Omicron) proteins as antigens to elicit a broad-spectrum immunity. The biological experiments indicated that the nano-MnP could effectively activate antigen-presenting cells through the cGAS-STING pathway. Compared with the conventional Alum-adjuvanted group, the nano-MnP-adjuvanted bivalent vaccine elicited approximately 7- and 8-fold increases in IgG antibody titers and antigen-specific IFN-γ secreting T cells, respectively. Importantly, antisera of the nano-MnP-adjuvanted group could effectively cross-neutralize the SARS-CoV-2 and its five variants of concern (VOCs) including Alpha, Beta, Gamma, Delta, and Omicron, demonstrating that this bivalent vaccine based on S1-WT and S1-Omicron proteins is an effective vaccine design strategy to induce broad-spectrum immune responses. Collectively, this nano-MnP material may provide a novel and efficient adjuvant platform for various prophylactic and therapeutic vaccines and provide insights for the development of the next-generation manganese adjuvant.

Traditional Chinese Medicine Constitution Is Associated with the Frailty Status of Older Adults: A Cross-Sectional Study in the Community.

Objective: This study explored the relationship between traditional Chinese medicine (TCM) constitution and frailty status in older adults. Methods: A total of 3,586 participants, 65 years of age and older, with complete data were evaluated. All received a complete frailty assessment and completed a TCM geriatric constitution questionnaire. Baseline characteristics and demographic information were collected. The relationship between the TCM constitution and frailty was evaluated by binary regression analysis. The consistency of the result was tested by multivariate linear regression. Results: The average prevalence of frailty among older adult participants was 12.5%. The three most prevalent biased constitutions in the frail older adult participants were phlegm dampness 140 (31.3%), Yin deficiency 77 (17.2%), and Yang deficiency 47 (10.5%). Univariate analysis showed that TCM constitution significantly correlated with frailty. After adjusting for potential confounders, binary logistic regression found a significant correlation between biased constitutions and frailty, including Qi stagnation (odds ratio (OR) = 3.51, 95% confidence interval (CI): 1.94-6.36)), Qi deficiency ((OR = 3.23, (95% CI: 1.76-5.94)), Yang deficiency ((OR = 2.37, (95% CI: 1.50-3.74)), phlegm dampness ((OR = 1.75, (95% CI: 1.24-2.48)), and Yin deficiency ((OR = 1.70, (95% CI: 1.15-2.50)). Results of multiple linear regression were consistent. Conclusions: TCM constitution was significantly associated with frailty status in older adults, and the distribution was different. Compared with a neutral constitution, older adults with Qi stagnation, Qi deficiency, Yang deficiency, phlegm dampness, and Yin deficiency were more likely to experience frailty.