[Protective effect of anti-idiopathic pulmonary fibrosis drug Pirfenidone and Sufenidone (SC1011) on pulmonary injury induced by tuberculosis in a mouse tuberculosis model].

Objective: To evaluate the protective effect of anti-idiopathic pulmonary fibrosis (IPF) marketed drug Pirfenidone and its clinical drug Sufenidone (SC1011) against lung injury in a mouse tuberculosis model. Methods: C57BL/6 mouse model of tuberculosis was established. A total of 75 C57BL/6 mice were infected with 1×107 CFU/ml H37Rv suspension by aerosol and randomly divided into untreated (n=9) group, isoniazid+rifampicin+pyrazinamide (HRZ) group (n=22), PFD+HRZ group (n=22), and SC1011+HRZ group (n=22). C57BL/6 mice were infected with H37Rv by aerosol for 6 weeks and then treated. Seven mice in each treatment group were weighed, sacrificed, dissected and observed for lung and spleen lesions at 4 and 8 weeks of treatment. HE staining and Masson staining were used to assess degree of lung injury and fibrosis, respectively. ELISA was used to assess the IFN-γ/TNF-α content in the serum of mice in each treatment group after 4 weeks of treatment. Hydroxyproline (HYP) content in lung tissue was measured by alkaline hydrolysis; meanwhile, CFU counts were used to assess the bacterial load in the lung and spleen of mice in each treatment group and the recurrence of spleen and lung tissue after 12 weeks of drug withdrawal. Results: At 8 weeks, the HYP content in the lung tissue was (630±58), (635±17), and (840±70) µg/mg in the PFD+HRZ, SC1011+HRZ, and HRZ treatment group, respectively (P<0.05).At 8 weeks, the proportion of Masson staining blue-stained area, that was, positive area, in lung tissue was 16.65%±1.82%, 10.01%±2.16%, and 21.36%±3.21%, respectively (F=27.11, P<0.001).The lung injury scores by HE staining at 8 weeks were (5.00±0.50), (5.00±0.47), and (6.89±0.99) points, respectively (F=19.81, P<0.001).The results of 4-week ELISA showed that the levels of TNF-α and IFN-γ in the serum of the SC1011+HRZ-treated group were lower than those of the HRZ-treated group (all P<0.05).The degree of lung injury and fibrosis in PFD+HRZ and SC1011+HRZ treatment groups were lower than those in HRZ treatment group (all P<0.001). The number of viable bacteria in the lung tissue of mice treated with PFD+HRZ, SC1011+HRZ, and HRZ for 4 weeks was lower than that of mice untreated [(1.82±0.10), (1.91±0.05), (1.79±0.17) vs. (5.27±0.07) lg(CFU+1)/ml, all P<0.05)]. And the aseptic transformation of the spleen of mice was achieved in each treatment group at 8 weeks of administration. After 12 weeks of drug withdrawal, the recurrence of lung infection in the SC1011+HRZ treatment group was 3/7 lower than 5/7 in the HRZ treatment group (P>0.05); the recurrence of spleen infection in the SC1011+HRZ treatment group was 1/7 lower than 5/7 in the HRZ treatment group (P>0.05).Pulmonary infection recurred more frequently in PFD+HRZ 6/7 versus HRZ 5/7 (P>0.05). Conclusions: PFD/SC1011, when combined with HRZ, reduced lung injury and reduced secondary fibrosis in pulmonary tuberculosis in C57BL/6 mice. SC1011 combined with HRZ has no significant short-term therapeutic effect on MTB, but may reduce its recurrence rate in long-term treatment, especially in reducing the recurrence rate of mouse spleen.

[Study on the pharmacodynamic activity of combinations with the new anti-tuberculosis drug pyrifazimine in vitro and in vivo in mouse].

Objective: To evaluate two-drug combination interaction between pyrifazimine(TBI-166) and anti-drug-resistant tuberculosis group A drugs Bedaquiline (BDQ), Moxifloxacin (MFX) and the new anti-tuberculosis drug Delamanid (DLM), SQ109, Q203, and PBTZ169 in vitro and in vivo in mouse, so as to provide basis for TBI-166 combination therapy. Methods: This study was performed from September 2020 to July 2021. The chessboard method was used to evaluate the interaction between TBI-166 and BDQ, MFX, DLM, SQ109, and PBTZ169. The time-killing kinetics method was used to evaluate the anti-tuberculosis activity of the two-drug combination with partial synergy. The BALB/c mouse acute infection model was used to evaluate the anti-tuberculosis activity at 4 and 8 weeks in the two-drug combination group (TBI-166+BDQ, TBI-166+SQ109, TBI-166+PBTZ169, TBI-166+Q203) and monotherapy groups (TBI-166, BDQ, SQ109, PBTZ169, Q203). Data analysis was performed using an independent sample t-test. Results: After TBI-166 combined with anti-tuberculosis drugs, MIC was reduced to 6.25% to 25.00% of TBI-166 monotherapy. After TBI-166 combined with BDQ, SQ109 and PBTZ169, the partial inhibitory concentration index (FICI) values were 0.53, 0.75 and 0.75, respectively; the time sterilization experiment showed that the viable population of Mycobacterium tuberculosis treated with two-drug combination of TBI-166 and BDQ, SQ109, PBTZ169 for 14 days decreased at least 3 log10 CFU/ml. In the mouse experiments, it was found that, the amount of viable bacteria in lung tissue of BDQ, SQ109 and PBTZ169 combined with TBI-166 groups was lower than that of the monotherapy group,respectively. The lung tissue culture of mice in the TBI-166+BDQ group was negative after 4 weeks of treatment, and the number of live bacteria in the lungs of the TBI-166+BDQ group was 1.49 log10CFU lower than that of the BDQ monotherapy group(P<0.01). Conclusion: In vitro and in vivo experiments in mice revealed that TBI-166 had synergistic anti-tuberculosis activity after being combined with BDQ, SQ109 and PBTZ169, respectively.

Identification of a major quantitative trait locus for ear size induced by space flight in sweet corn.

The development of molecular markers has contributed to progress in identifying the gene(s) responsible for favorable variations in maize studies. In this study, quantitative trait locus (QTL) mapping was conducted using simple sequence repeat markers in an F2 sweet corn population from a cross between parental line 1132 and space flight-induced mutant line 751 to identify the loci contributing to an increase in some yield traits. A primary mutated genomic region was located on chromosome 9. In total, 26 QTL were detected for eight yield-related traits and assembled into three clusters on chromosome 9. The largest QTL cluster at bin 9.02/03, primarily contributing to >10% of the phenotypic variation in ear and cob diameters, was likely due to a major QTL. Desired alleles of these QTL were provided by the mutant line 751. The primary action of the major mutant allele was an additive effect. Another mutant locus, which was induced in bin 9.01, increased cob and ear diameters by dominant genetic action.

Global trends in coronary artery disease and artificial intelligence relevant studies: a bibliometric analysis.

OBJECTIVE: Coronary artery disease (CAD) is a major global cause of death, greatly affecting life expectancy and quality of life for populations. With the advent of artificial intelligence (AI), there is new hope for accurately managing CAD. While recent studies have shown remarkable progress in AI and CAD research, there is a gap in comprehensive bibliometric analysis in this field. Therefore, this study aims to provide a thorough analysis of trends and hotspots in AI and CAD-related research utilizing bibliometrics. MATERIALS AND METHODS: Publications on AI and CAD relevant research from 2009 to 2023 were searched through the WoS core database (WoSCC). CiteSpace, VOSviewer and Excel 365 were used to conduct the bibliometric analysis. RESULTS: The bibliometric analysis included 1,248 publications, indicating a steady increase in AI and CAD-related publications annually. The United States of America (USA), China, and Germany were identified as the most influential countries in this field. Research institutions such as Cedars Sinai Med Ctr, Med Univ South Carolina, Harvard Med Sch and Capital Med Univ were the main contributors to research production. FRONT CARDIOVASC MED is the top-ranked journal, while J AM COLL CARDIOL emerged as the most cited journal. Schoepf, U. Joseph, Slomka, Piotr J., Berman, Daniel S. and Dey, Damini were the most prolific authors, while U. Rajendra Acharya was the most frequently co-cited author. Research related to the AI calculation of coronary flow reserve fraction and coronary artery calcification, based on coronary CT to identify CAD and cardiovascular risk, was a key research topic in this field. The potential link between cardiovascular risk stratification and radiomics is currently at the forefront of the field. CONCLUSIONS: This study is the first to use a bibliometric approach to visualize and analyze AI and CAD-related research. The findings provide insights into recent research trends and hotspots in the field and can serve as a reference for scholars to identify critical issues in this field.