The H102-loaded liposome prepared in this study for nasal administration is stable, effective and safe, which has great potential for AD treatment.

Background: The etiology and pathogenesis of granulomatous lobular mastitis (GLM) remain unknown, with no unified evaluation criteria or standard treatments. This study aimed to assess the etiology and features of GLM, as well as the effects of surgery (lesion excision + stage I breast reconstruction; LE + BR) for GLM.Methods: This study evaluated 178 female GLM patients retrospectively in 2006-2015. The surgery and non-surgery groups included 164 and 14 patients, respectively. All patients received conservative therapy (traditional Chinese medicine combined with regional wet compress and pus drainage). In addition, the surgery group (n=164) underwent LE + BR. Clinical data, including disease course, causes, lesion size, marital status, and treatment approaches, were assessed.Results: Follow-up was 13-117 months. Seventy-five of the 178 patients had no overt causes (42.1%); meanwhile, 63 (35.4%) and 16 (9.0%) had congenital nipple retraction and a history of psychotropic drugs for >1 year, respectively. The surgery group showed lesions significantly shrunk (≤1 quadrant) with acute inflammation fully controlled; 8 showed recurrence, indicating a cure rate of 95.1% (156/164). In the nonsurgery group, 4 cases showed relapse after 6-14 months (cure rate =71.4%; 10/14). Therefore, surgical treatment was significantly more efficient than non-surgical treatment (P=0.001). Kaplan-Meier survival curves for the two treatment types showed a significant difference in recurrence (log rank =11.84, P<0.001). Conclusions:In GLM patients, LE + BR is safe and effective with respect to cosmetic results, recovery time, and recurrence. Successful surgery should be performed for patients whose lesions ≤1 quadrant, aim to achieve optimal GLM treatment.

β-amyloid hypothesis is the predominant hypothesis in the study of pathogenesis of Alzheimer's disease. This hypothesis claims that aggregation and neurotoxic effects of amyloid β (Aβ) is the common pathway in a variety of etiological factors for Alzheimer's disease. Aβ peptide derives from amyloid precursor protein (APP). β-sheet breaker peptides can directly prevent and reverse protein misfolding and aggregation in conformational disorders. Based on the stereochemical structure of Aβ1-42 and aggregation character, we had designed a series of β-sheet breaker peptides in our previous work and screened out a 10-residue peptide β-sheet breaker peptide, H102. We evaluated the effects of H102 on expression of P-tau, several associated proteins, inflammatory factors and apoptosis factors, and examined the cognitive ability of APP transgenic mice by behavioral test. This study aims to validate the β-amyloid hypothesis and provide an experimental evidence for the feasibility of H102 treatment for Alzheimer's disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially emerging variants, poses an increased threat to global public health. The significant reduction in neutralization activity against the variants such as B.1.351 in the serum of convalescent patients and vaccinated people calls for the design of new potent vaccines targeting the emerging variant. However, since most vaccines approved and in clinical trials are based on the sequence of the original SARS-CoV-2 strain, the immunogenicity and protective efficacy of vaccines based on the B.1.351 variant remain largely unknown. In this study, we evaluated the immunogenicity, induced neutralization activity, and protective efficacy of wild-type spike protein nanoparticle (S-2P) and mutant spike protein nanoparticle (S-4M-2P) carrying characteristic mutations of B.1.351 variant in mice. Although there was no significant difference in the induction of spike-specific IgG responses in S-2P- and S-4M-2P-immunized mice, neutralizing antibodies elicited by S-4M-2P exhibited noteworthy, narrower breadth of reactivity with SARS-CoV-2 variants compared with neutralizing antibodies elicited by S-2P. Furthermore, the decrease of induced neutralizing antibody breadth at least partly resulted from the amino acid substitution at position 484. Moreover, S-4M-2P vaccination conferred insufficient protection against live SARS-CoV-2 virus infection, while S-2P vaccination gave definite protection against SARS-CoV-2 challenge in mice. Together, our study provides direct evidence that the E484K substitution in a SARS-CoV-2 subunit protein vaccine limited the cross-reactive neutralizing antibody breadth in mice and, more importantly, draws attention to the unfavorable impact of this mutation in spike protein of SARS-CoV-2 variants on the induction of potent neutralizing antibody responses.

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