Seven novel linear polyketides,talaketides A-G(1-7),were isolated from the rice media cultures of the mangrove sed-iment-derived fungus Talaromyces sp.SCSIO 41027.Among these,talaketides A-E(1-5)represented unprecedented unsaturated lin-ear polyketides with an epoxy ring structure.The structures,including absolute configurations of these compounds,were elucidated through detailed analyses of nuclear magnetic resonance(NMR)and high-resolution mass spectrometry(HR-MS)data,as well as elec-tronic custom distributors(ECD)calculations.In the cytotoxicity screening against prostate cancer cell lines,talaketide E(5)demon-strated a dose-dependent inhibitory effect on prostate cancer PC-3 cell lines,with an IC50 value of 14.44 μmol·L-1.Moreover,com-pound 5 significantly inhibited the cloning formation of PC-3 cell lines and arrested the cell cycle in S-phase,ultimately inducing ap-optosis.These findings indicate that compound 5 may serve as a promising lead compound for the development of a potential treat-ment for prostate cancer.

【Objective】 To explore the effect mechanism of Salvia miltiorrhiza and safflower on combined anti-ischemic stroke and verify relevant action targets in middle cerebral artery occlusion (MCAO) rat model based on network pharmacology. 【Methods】 ①Traditional Chinese Medicine Systems Pharmacology (TCMSP) and GeneCards databases were used to screen the active components, component targets and ischemic stroke targets of Salvia miltiorrhiza and safflower respectively. The above data were imported into STRING database for protein interaction network analysis, and Cytoscape3.8.0 software was used to construct protein interaction network (PPI) and component target interaction network. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation analysis of target genes were performed using David online analysis tool. ② In this experiment, a rat model of ischemic stroke was prepared by using improved MCAO method, and immunohistochemical method and Real-time quantitative polymerase chain reaction (REAL-TIME PCR) to detect the positive expressions of NLRP3 inflammatory body and NF P65 protein in the brain tissue of rats in each group so as to explore the functional mechanism of anti-inflammation reaction against cerebral ischemia injury. 【Results】 ① A total of 87 effective components, corresponding to 253 targets, 1448 targets for ischemic stroke and 161 targets related to drugs and diseases, were screened from the Salvia milticorrhiza and safflower drug pairs. We obtained 730 biological processes, 81 cell components and 128 molecular functions through GO analysis, and 127 signal pathways through KEGG analysis. ②Immunohistochemical method and Real-time PCR determination results showed that compared with control group rats, model group rats had significantly increased tissue NLRP3 inflammatory body and NFkBp65 protein expressions (P<0.01). Compared with those in the model group, NLRP3 inflammatory body and NFkBp65 protein expressions significantly decreased in Dan red compatibility groups and nim horizon groups (P<0.01). 【Conclusion】 Compatibility of effective components in salvia miltiorrhiza, and carthamus tinctorius can further downregulate the release of inflammatory corpuscle NLRP3 through NFkB signaling pathway by blocking inflammatory lesions and thus plays the role of fighting against inflammatory damage.

Stomach exuberance and spleen deficiency are common pathogenesis of many metabolic diseases. Through analyzing the pathogenesis of stomach exuberance and spleen deficiency， it is believed that its essence is stomach heat and spleen deficiency. Stomach heat includes gastrointestinal heat， spleen and stomach damp-heat， and spleen deficiency is divided into deficiency of spleen yin， deficiency of spleen qi ， and deficiency of spleen yang. It is suggested that the metabolic diseases of stomach-exuberance and spleen-deficiency syndrome can be divided into three categories，i.e. stomach-heat and spleen yin-deficiency， stomach-heat and spleen qi-deficiency， and stomach-heat and spleen yang-deficiency， and the main treatment methods are clearing and draining heat， nourishing yin and moistening intestine， clearing dampness and heat， strengthening spleen and qi， clearing dampness and heat， strengthening spleen and warming yang， respectively， with prescriptions as Maziren Pills （麻子仁丸）， Qinlian Pingwei Powder （芩连平胃散）， and Jiawei Lianli Decoction （加味连理汤） accordingly.

The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC₅₀ = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC₅₀ = 1.513 μmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 μg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 ( 5) and AZD5099 ( 6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 ( 6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 μg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.