Biology subjects

He, G.

Publications and source records attributed to He, G..

2 recordsLinked to original sources

bioRxiv2018

Cycloserine for Treatment of Multidrug-Resistant Tuberculosis in China: A Retrospective Observational Study

ObjectivesCycloserine is crucial in multidrug-resistant tuberculosis (MDR-TB) treatment. Although extensive research has been carried out on MDR-TB, most researchers have not treated cycloserine in much detail. Therefore, we evaluate the efficacy and safety of cycloserine and seek to clarify the role of cycloserine for treatment of simple MDR-TB, pre-extensively drug-resistant tuberculosis (pre-XDR-TB), and extensively drug-resistant tuberculosis (XDR-TB).\n\nPatients and methodsA retrospective observational study was performed in China. We determined the treatment outcome as the primary outcome for 144 cycloserine-treated and 181 cycloserine-nontreated patients according to the definitions of WHO. The proportion of patients with sputum-culture conversion and the frequency of adverse drug reactions related to cycloserine were assessed as well.\n\nResultsAmong 325 MDR-TB patients, 144 were treated with cycloserine and 100 (69.4%) out of 144 successfully completed treatment. Compared with patients in non-cycloserine group, the hazard ratio of any unfavorable treatment outcome was 0.53 (95%CI: 0.35-0.81, P=0.003). Culture conversion rate at the intensive phase was similar whether cycloserine was administered or not (P=0.703). Of the 144 patients treated with cycloserine, a total of 16 (11.1%) patients experienced side-effects related to cycloserine, including 7 patients who discontinued cycloserine permanently.\n\nConclusionsCycloserine could be an attractive agent to treat MDR-TB. Its safety profile warrants use in the most of MDR-TB cases. Cycloserine significantly improved the chance of favorable outcome for patients with simple MDR-TB but not pre-XDR-TB and XDR-TB. More aggressive regimens might be required for pre-XDR-TB or XDR-TB patients.

microbiology↗

bioRxiv2017

CRISPR/Cas9-mediated resistance to cauliflower mosaic virus

Viral diseases are a leading cause of worldwide yield losses in crop production. Breeding of resistance genes (R gene) into elite crop cultivars has been the standard and most cost-effective practice. However, R gene-mediated resistance is limited by the available R genes within genetic resources and in many cases, by strain specificity. Therefore, it is important to generate new and broad-spectrum antiviral strategies. The CRISPR-Cas9 (clustered regularly interspaced palindromic repeat, CRISPR-associated) editing system has been employed to confer resistance to human viruses and several plant single-stranded DNA geminiviruses, pointing out the possible application of the CRISPR-Cas9 system for virus control. Here we demonstrate that strong viral resistance to cauliflower mosaic virus (CaMV), a pararetrovirus with a double-stranded DNA genome, can be achieved through Cas9-mediated multiplex targeting of the viral coat protein sequence. We further show that small interfering RNAs (siRNA) are produced and mostly map to the 3' end of guide RNAs (gRNA), although very low levels of siRNAs map to the spacer region as well. However, these siRNAs are not responsible for the inhibited CaMV infection because there is no resistance if Cas9 is not present. We have also observed edited viruses in systematically infected leaves in some transgenic plants, with short deletions or insertions consistent with Cas9-induced DNA breaks at the gRNA target sites in coat protein coding sequence. These edited coat proteins, in most cases, led to earlier translation stop and thus, non-functional coat proteins. We also recovered wild-type CP sequence in these infected transgenic plants, suggesting these edited viral genomes were packaged by wild-type coat proteins. Our data demonstrate that the CRISPR-Cas9 system can be used for virus control against plant pararetroviruses with further modifications.

plant biology↗