Objective To analyze the characteristics of the rpoB, KatG and inhA genes mutations in rifampin and isoniazid resistant Mycobacterium tuberculosis (MTB) clinical isolates in Baise district, Guangxi autonomous region. Methods 128 MTB clinical strains were collected and isolated for drug susceptibility testing, and drug resistant strain DNA was subtracted for rpoB, KatG and inhA genes mutation analysis. Results 75%(27/36)isolates carried mutations in the rpoB gene,and 59.3%(16/27)isolates carried mutations in 531 sites. 44.1%(15/34) isolates carried mutations in KatG or inhA, and 66.7%(10/15) isolates appeared in KatG 315 site, with two new mutations found in KatG 279 and 427 site. In these mutation isolates, 13.3%(2/15) mutations appeared in inhA 5, 6.7%(1/15) in inhA 16, and 20%(3/15) in both katG and inhA. Conclusions The mutation of rpoB, katG and inhA genes in TB is highly correlated with its resistance to rifampin and isoniazid in Baise district, Guangxi autonomous region. The study will provide a basis for further understanding the anti-bacterium mechanism and quick diagnostic methods for drug-resistant tuberculosis.

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.