Chaetoxylariones A-G: undescribed chromone-derived polyketides from co-culture of Chaetomium virescens and Xylaria grammica enabled via the molecular networking strategy.

By co-culturing two endophytic fungi (Chaetomium virescens and Xylaria grammica) collected from the medicinal and edible plant Smilax glabra Roxb. and analyzing them with MolNetEnhancer module on GNPS platform, seven undescribed chromone-derived polyketides (chaetoxylariones A-G), including three pairs of enantiomer ones (2a/2b, 4a/4b and 6a/6b) and four optical pure ones (1, 3, 5 and 7), as well as five known structural analogues (8-12), were obtained. The structures of these new compounds were characterized by NMR spectroscopy, single-crystal X-ray diffraction, 13C NMR calculation and DP4+ probability analyses, as well as the comparison of the experimental electronic circular dichroism (ECD) data. Structurally, compound 1 featured an unprecedented chromone-derived sulfonamide tailored by two isoleucine-derived δ-hydroxy-3-methylpentenoic acids via the acylamide and NO bonds, respectively; compound 2 represented the first example of enantiomeric chromone derivative bearing a unique spiro-[3.3]alkane ring system; compound 3 featured a decane alkyl side chain that formed an undescribed five-membered lactone ring between C-7' and C-10'; compound 4 contained an unexpected highly oxidized five-membered carbocyclic system featuring rare adjacent keto groups; compound 7 featured a rare methylsulfonyl moiety. In addition, compound 10 showed a significant inhibition towards SW620/AD300 cells with an IC50 value of PTX significantly decreased from 4.09 µM to 120 nM, and a further study uncovered that compound 10 could obviously reverse the MDR of SW620/AD300 cells.

Application of GeneXpert MTB/RIF technology in rifampicin resistance gene mutation of Mycobacterium tuberculosis / 中国热带医学

@#Abstract: Objective To analyze the accuracy and feasibility of GeneXpert MTB/RIF (GeneXpert) detection in the detection of Mycobacterium tuberculosis and the characteristics of rifampicin-resistant rpoB gene mutations. Methods A total of 4 234 sputum samples from suspected tuberculosis patients diagnosed in Sanya tuberculosis designated hospitals from 2015 to 2021 were selected and subjected to sputum smear, solid culture, drug sensitivity test by solid proportion method and GeneXpert detection. Results The positive detection rates of sputum smear, solid culture and GeneXpert of 4 234 sputum samples were 29.24% (1 238/4 234), 32.17% (1 362/4 234) and 35.40% (1 499/4 234), respectively. The positive detection rate of GeneXpert was higher than that of sputum smear, and the difference was statistically significant (χ2=36.775, P<0.01). It was slightly higher than solid culture, and the difference was not statistically significant (χ2=9.908, P=0.02). Taking solid culture results as the gold standard, the sensitivity and specificity of GeneXpert for detecting MTB were 91.04% (1 240/1 362) and 90.98% (2 613/2 872), respectively. According to the proportional drug susceptibility test results as the gold standard, the sensitivity and specificity of GeneXpert in detecting rifampicin resistance were 96.96% (96/99) and 98.86% (1 128/1 141), respectively, with the consensus rate of 98.71%. The accuracy of rifampicin resistance in GeneXpert group without probe mutation was significantly lower than that in group with probe mutation. There was a statistical difference in probe mutation frequency between newly treated and retreated cases. The analysis of rpoB gene mutation frequency characteristics showed: Probe E (50.00%) > Probe A (22.12%) > Probe D (14.42%) > Probe B (6.73%) > combined probe (5.77%) > Probe C (0.96%). Conclusions GeneXpert detection can quickly and effectively diagnose rifampicin-resistant tuberculosis, which is helpful for early clinical diagnosis and treatment. In this region, the rpoB gene mutation probes of rifampicin-resistant tuberculosis mainly occurr in Probe E and Probe A, with the least mutations in Probe C.

The function of glucose metabolism in embryonic diapause of annual killifish.

Annual killifish could survive as diapaused embryos buried in soil during dry seasons. When the embryos in diapause III were incubated in water, the larvae could be hatched quickly. However, the mechanism of diapause and hatching of annual killifish was ambiguous. In the present study, Nothobranchius guentheri were used as the model to clarify the physiological mechanism of diapause and hatching of annual killifish. The results indicated that incubation with water could significantly enhance the heart rate and blood circulation of embryos. To clarify the molecular mechanism, the transcriptomic analysis was used to compare the embryos in diapause I, diapause III, and hatching period. The results showed that DNA replication-related genes, cell division cycle 45 and proliferating cell nuclear antigen were more highly expressed in diapause I compared to diapause III. In addition, the transcript levels of glucagon, glucokinase and phosphofructokinase were more abundantly detected in hatching period compared to diapause III, but insulin receptor and insulin-like growth factor-binding protein were lower. These results indicated glucose metabolism might play an important role in diapause and hatching of killifish. To further confirm this result, several reagents involved in glucose metabolism were used to incubate embryos in diapause III. The results displayed that glucose and glucagon could both shorten the hatching time of embryos. In contrast, 2-deoxy-d-glucose, metformin, and insulin could prolong the hatching time and reduce the hatching rate. The results further confirmed that glucose metabolism played an important role in the diapause and hatching of annual killifish.

Disulfiram attenuates MCMV-Induced pneumonia by inhibition of NF-κB/NLRP3 signaling pathway in immunocompromised mice.

Cytomegalovirus (CMV) pneumonia in immunocompromised individuals is associated with damaging hyperinflammation and leads to high morbidity and mortality. It is urgently needed to develop new strategies to treat CMV-induced pneumonia. As disulfiram (DSF) reportedly inhibits inflammatory responses in different disease models, its therapeutic effects in CMV-induced pneumonia are proposed. In this study, we demonstrated that DSF effectively attenuated pulmonary injury and improved survival in murine CMV (MCMV) pneumonia model. DSF treatment inhibited lung inflammatory responses, e.g. reducing pro-inflammatory cytokines, upregulating anti-inflammatory cytokine, and lowering the accumulation of leukocytes in the lung. Similar to the in vivo results, DSF attenuated inflammatory responses and modulated NF-κB/NLRP3 inflammasome activation in MCMV-infected BMDMs. Furthermore, DSF reduced pulmonary fibrosis and viral loads in MCMV pneumonia mice and BMDMs. The mechanism of anti-inflammatory effects of DSF may due to its regulating NF-κB signaling and NLRP3 inflammasome activation. Collectively, our results suggest that DSF-mediated anti-hyperinflammatory effects have potentials for therapy of human CMV pneumonia.