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Aspirin can efficiently inhibit liver cancer growth, but the mechanism is poorly understood. In this study, we report that aspirin modulates glucose uptake through downregulating glucose transporter 1 (GLUT1), leading to the inhibition of hepatoma cell proliferation. Our data showed that aspirin significantly decreased the levels of reactive oxygen species (ROS) and glucose consumption in hepatoma cells. Interestingly, we identified that GLUT1 and HIF1α could be decreased by aspirin. Mechanically, we demonstrated that the -1008/-780 region was the regulatory element of transcriptional factor NF-κB in GLUT1 promoter by luciferase report gene assays. PDTC, an inhibitor of NF-κB, could suppress the expression of GLUT1 in HepG2 and H7402 cells, followed by affecting the levels of ROS and glucose consumption. CoCl 2 -activated HIF1α expression could slightly rescue the GLUT1 expression inhibited by aspirin or PDTC, suggesting that aspirin depressed GLUT1 through targeting NF-κB or NF-κB/HIF1α signaling. Moreover, we found that GLUT1 was highly expressed in clinical HCC tissues relating to their paired adjacent normal tissues. Importantly, we observed that high level of GLUT1 was significantly correlated with the poor relapse-free survival of HCC patients by analysis of public data. Functionally, overexpression of GLUT1 blocked the PDTC-induced or aspirin-induced inhibition of glucose metabolism in HepG2 cells. Conversely, aspirin failed to work when GLUT1 was stably knocked down in the cells. Administration of aspirin could depress the growth of hepatoma cells through controlling GLUT1 in vitro and in vivo. Thus, our finding provides new insights into the mechanism by which aspirin depresses liver cancer.

Aim： To determine how the relative amino acid contents and metabolic pathways regulate the pharmacological phenotypes in rats with cerebral ischemia after treatment with varying doses of DanHong injection （DHI）. Methods： Adult male rats underwent middle cerebral artery occlusion （MCAO）, and were injected with DHI （DH-1： 1 mL/kg; DH-2： 2.5 mL/kg; DH-3：5 mL/kg, and DH-4：10 mL/kg, iv） daily for 3 d. The neurological deficit score, body weights and infarct volume were assessed. Serum levels of 20 free amino acids were determined using HPLC, and the values were transformed through the quantitative analysis of the amino acids in the serum metabolic spectrum. Multivariate statistical analysis methods （PCA and PLS-DA） and web-based metabolomics tools （MetPa and MetaboAnalyst） were used to analyze the biological data sets for the amino acids. Results： Administration of DHI dose-dependently decreased cerebral infarct volume, and ameliorated neurological deficits. A total of 5, 6, 7 and 7 non-overlapping metabolites were identified in the DH-1, DH-2, DH-3, and DH-4 groups, respectively. Eight metabolites were shared between the DHI groups and the vehicle group. In addition, the serum levels of glutamic acid, aspartic acid and serine increased with increasing DHI dose. A total of 3, 2, 2 and 5 non-overlapping metabolic pathways were identified in the DH-1, DH-2, DH-3 and DH-4 groups, respectively, and glycine, serine, threonine and histidine metabolism were identified as overlapping pathways among the 4 dose groups. Conclusion： Overlapping and non-overlapping amino acid metabolites and metabolic pathways are associated with the dose-dependent neuroprotective effect of DHI.

A series of new paclitaxel-benzoxazoles hybrids were designed based on both the molecular docking mode of beta-tubulin with paclitaxel derivatives ( 7a and 7g ), and the activity-structure relationship of C-13 side chain in paclitaxel. Palladium-catalyzed direct Csp 2 –H arylation of benzoxazoles with different aryl-bromides was used as the key synthetic strategy for the aryl-benzoxazoles moieties in the hybrids. Twenty-six newly synthesized hybrids were screened for their antiproliferative activity against human cancer cell lines such as human breast cancer cells (MDA-MB-231) and liver hepatocellular cells (HepG2) by the MTT assay and results were compared with paclitaxel. Interestingly, most hybrids ( 7a – 7e , 7i , 7k , 7l , 7A , 7B , 7D and 7E ) showed significantly active against both cell lines at concentration of 50 µM, which indicated that the hybrid strategy is effective to get structural simplified paclitaxel analogues with high anti-tumor activity.

Although the general pathway of sex pheromone synthesis in moth species has been established, the molecular mechanisms remain poorly understood. The common cutworm Spodoptera litura is an important agricultural pest worldwide and causes huge economic losses annually. The female sex pheromone of S. litura comprises Z9,E11-14:OAc, Z9,E12-14:OAc, Z9-14:OAc, and E11-14:OAc. By sequencing and analyzing the transcriptomic data of the sex pheromone glands, we identified 94 candidate genes related to pheromone biosynthesis (55 genes) or chemoreception (39 genes). Gene expression patterns and phylogenetic analysis revealed that two desaturase genes (SlitDes5 and SlitDes11) and one fatty acyl reductase gene (SlitFAR3) showed pheromone gland (PG) biased or specific expression, and clustered with genes known to be involved in pheromone synthesis in other moth species. Furthermore, 4 chemoreception related genes (SlitOBP6, SlitOBP11, SlitCSP3, and SlitCSP14) also showed higher expression in the PG, and could be additional candidate genes involved in sex pheromone transport. This study provides the first solid background information that should facilitate further elucidation of sex pheromone biosynthesis and transport, and indicates potential targets to disrupt sexual communication in S. litura for a novel pest management strategy.

Background Brucellosis is an endemic disease in the Inner Mongolia Autonomous Region of China and Ulanqab exhibits the highest prevalence of brucellosis in this region. Due to the complex nature of Brucellosis, a cure for this disease has proven to be elusive. Furthermore, the reduced susceptibility of Brucella spp. to antimicrobial agents has been reported as a potential cause of therapeutic failure. However, detailed in vitro antimicrobial susceptibility patterns pertaining to Brucella isolates from this region have not yet been published. The aim of this study was to evaluate the antibiotic susceptibility profile of Brucella melitensis clinical isolates from Ulanqab, Inner Mongolia, China. Methods A total of 85 B. melitesis isolates were obtained from humans in Ulanqab of Inner Mongolia, China; the antimicrobial susceptibility of 85 clinical isolates to nine antibiotics was assessed using the E-test method according to the CLSI (Clinical and Laboratory Standards Institute) guidelines. Results All of the tested isolates were susceptible to minocycline, sparfloxacin, doxycycline, tetracycline, ciprofloxacin, gentamicin and levofloxacin. Resistance to rifampin and cotrimoxazole was observed in 1.0% (1/85) and 7.0% (6/85) of the isolates, respectively. However, rpoB gene mutations were not observed in single isolates exhibiting resistance to rifampin. Conclusions We observed that B. melitensis isolates are susceptible to the majority of the tested antibiotics. Furthermore, minocycline and sparfloxacin exhibited extremely high bactericidal effects in relation to the B. melitensis isolates. The sensitivity of commonly used drugs for the treatment of brucellosis should be regularly monitored. To the best of our knowledge, this is the first report of rifampin and cotrimoxazole resistant isolates of B. melitensis in China. In summary, based on the findings from this study, we suggest that antibiotic administration and use should be rationalized to prevent future drug resistance.

Multidrug-resistant (MDR) bacterial infections have emerged as a significant threat to global public health, with antibiotic resistance mechanisms—such as alterations in bacterial membrane permeability—substantially limiting therapeutic options and exacerbating infection persistence. In this study, we developed a novel self-carrier nanodrug formulation by directly assembling antibiotic tobramycin (Tob) and antimicrobial borneol 4-formylbenzoate (BF) into Tob-BF nanodrugs (TBN) via dynamic Schiff base linkages, without the need for additional adjuvants. The resultant TBN exhibits minimal bactericidal activity under physiological conditions but undergoes decomposition and activation specifically within the microenvironment of bacterial infections. Confocal microscopy analysis demonstrates that TBN is preferentially taken up and accumulates intracellularly in multidrug-resistant Staphylococcus aureus (MDRSA) to a greater extent than either Tob or BF alone. In both in vitro and in vivo assays, TBN outperforms Tob, BF, and physically mixed Tob + BF (with equal dose to TBN) in terms of antibacterial efficacy, particularly in promoting the recovery of xenograft infection with MDRSA in mice. Collectively, these findings highlight the potential of our self-carrier nanodrug platform, which integrates two distinct antibacterial agents, as an innovative and effective strategy to overcome tobramycin resistance in MDRSA and eliminate MDRSA infections. A unique self-carrier nanodrug, Tob-BF nanodrugs (TBN), assembled via dynamic Schiff base linkages to overcome antibiotics resistance and robustly combat clinical xenograft MDR bacterial infections is presented. The increased bacterial uptake and intracellular accumulation of TBN lead to superior synergistically effect (FICI is 0.19). [Display omitted] •Self-carrier TBN is directly assembled from Tob and BF via a Schiff base linkages.•TBN exhibits minimal bactericidal activity under physiological conditions and responsively targets bacterial infections.•The response pattern endows TBN with a biomimetic fibrinogen response process.•TBN enhances bacterial uptake in MDRSA to overcome antibiotic resistancewithout inducing bacterial resistance.•Biomimetic self-carrier strategy rejuvenates ineffective antibiotics for treating clinically MDR bacterial infections.

Species-specific sex pheromone is biosynthesized and released in most female moths as a chemical cue in mating communication. However, information on genes involved in this pathway is limited. The beet armyworm, Spodoptera exigua , is a cosmopolitan agricultural pest that causes severe economic losses to many crops. In China, the female sex pheromones in sex pheromone glands (PGs) of S. exigua have been measured which comprises (Z,E)-9,12-tetradecadienyl acetate, (Z)-9-tetradecen-l-ol, (Z)-9-tetradecenyl acetate, and (Z,E)-9,12-tetradecadien-1-ol in a ratio of 47:18:18:17. Fifty-nine putative genes related to sex pheromone biosynthesis were identified in the present study by sequencing and analyzing the sex pheromone gland (PG) transcriptome of S. exigua . Expression profiles revealed that two desaturase ( SexiDes5 and SexiDes11 ) and three fatty acyl reductase ( SexiFAR2, 3 , and 9 ) genes had PG-specific expression, and phylogenetic analysis demonstrated that they clustered with genes known to be involved in pheromone synthesis in other moth species. Our results provide crucial background information that could facilitate the elucidation of sex pheromone biosynthesis pathway of S. exigua as well as other Spodoptera species and help identify potential targets for disrupting sexual communication in S. exigua for developing novel environment-friendly pesticides.

Although the general pathway of sex pheromone synthesis in moth species has been established, the molecular mechanisms remain poorly understood. The common cutworm Spodoptera litura is an important agricultural pest worldwide and causes huge economic losses annually. The female sex pheromone of S. litura comprises Z9,E11-14:OAc, Z9,E12-14:OAc, Z9-14:OAc, and E11-14:OAc. By sequencing and analyzing the transcriptomic data of the sex pheromone glands, we identified 94 candidate genes related to pheromone biosynthesis (55 genes) or chemoreception (39 genes). Gene expression patterns and phylogenetic analysis revealed that two desaturase genes (SlitDes5 and SlitDes11) and one fatty acyl reductase gene (SlitFAR3) showed pheromone gland (PG) biased or specific expression, and clustered with genes known to be involved in pheromone synthesis in other moth species. Furthermore, 4 chemoreception related genes (SlitOBP6, SlitOBP11, SlitCSP3, and SlitCSP14) also showed higher expression in the PG, and could be additional candidate genes involved in sex pheromone transport. This study provides the first solid background information that should facilitate further elucidation of sex pheromone biosynthesis and transport, and indicates potential targets to disrupt sexual communication in S. litura for a novel pest management strategy.