Due to the limitations of current anti-HBV therapies, the HBV core (HBc or HBcAg) protein assembly modulators (CpAMs) are believed to be potential anti-HBV agents. Therefore, discovering safe and efficient CpAMs is of great value. In this study, we established a HiBiT-based high-throughput screening system targeting HBc and screened novel CpAMs from an in-house marine chemicals library. A novel lead compound 8a, a derivative of the marine natural product naamidine J, has been successfully screened for potential anti-HBV activity. Bioactivity-driven synthesis was then conducted, and the structure‒activity relationship was analyzed, resulting in the discovery of the most effective compound 11a (IC₅₀ = 0.24 μmol/L). Furthermore, 11a was found to significantly inhibit HBV replication in multiple cell models and exhibit a synergistic effect with tenofovir disoproxil fumarate (TDF) and IFNa2 in vitro for anti-HBV activity. Treatment with 11a in a hydrodynamic-injection mouse model demonstrated significant anti-HBV activity without apparent hepatotoxicity. These findings suggest that the naamidine J derivative 11a could be used as the HBV core protein assembly modulator to develop safe and effective anti-HBV therapies.

This study was aimed to prepare the spraying agent of prescriptions of Miao nationality herb and investigate the effect of Miao nationality herbs spray for serum SOD, MDA, and expression of Fas and Caspase-3 mRNA in lung tissues of silica-treated rats. The healthy SD rats were divided into 5 groups. Silica dust suspension was used in the model establishment of 4 groups. After the model was successfully established, 3 groups were randomly selected and given glucocorticoids atomization inhalation, Miao nationality herbs spray, Miao nationality herbs spray combined with intragastric administration of herbal medicine, respectively. After 40-day treatment, water-solubletetrazolium salt (WST-1) was used in the detection of serum superoxide dismutase (SOD). Thiobarbituric acid (TBA) was used in the detection of malondialdehyde (MDA). The mRNA expression variance of the Fas and Caspase-3 were detected by RT-PCR. The results showed that compared with the silica dust suspension group, the SOD activity of serum in the Miao nationality herbs spray group was significantly increased (P< 0.05). MDA content and the mRNA of Fas and Caspase-3 were significantly lower in the Miao nationality herbs spray group (P< 0.05). It was concluded that Miao nationality herbs spray group was able to increase the SOD activity of serum, decrease MDA content, and obviously decrease the expression of Fas and Caspase-3 of lung tissues among silica dust suspension rats.

Objective To investigate the correlation between cornexin37 (Cx37) CI019T polymorphism and ischemic stroke and its outcome.Methods Restriction fragment length polymorphism analysis was used to detect the distribution of Cx37 C1019T polymorphism in a ischemic stroke group and a control group.The modified Rankin scale (mRS) was used to evaluate the neurological outcome at 3 months after onset.Results A total of 235 patients in the control group,and 232 patients in the ischemic stroke goup were recruited.In the ischemic stroke group,210 had a good outcome (mRS ＜3) and 22 had a poor outcome (mRS≥ 3).The TT genotype (12.93％ vs.6.39％ ; x2 =10.087,P =0.006) and T allele (31.25％ vs.21.49％ ; x2 =11.466,P=0.001) frequency in the ischemic stroke group were significantly higher than those in the control group.Multivariatelogistic regression analysis showed that TT genotype (odds ratio [OR] 5.794; 95％ confidence interval [CI] 1.405-23.894; P =0.015) and T allele (OR 131.016,95％ CI 6.943 -2 472.477; P =0.001)signifkantly increased the risk of ischemic stroke.Univariate analysis showed that TT genotype (OR 0.650,95％ CI 0.144 - 2,934; P =0.575),CT genotype (OR 0.622,95％ CI 0.234 - 1.655; P =0.342),and CC genotype (OR 0.654,95％ CI 0.268 - 1.595; P =0.350) had no significant correlation with the outcome of ischemic stroke.Conclusions Cx37 1019TT genotype and T allele may increase the risk of ischemic stroke.T allele is one of genetic susceptibility factors for ischemic stroke; however,its gene polymorphism is not associated with the outcome of ischemic stroke at 3 months after onset.