This study presents a novel intraoperative in vivo imaging approach which harnessed Cerenkov luminescence (CL) to detect primary and metastatic colorectal cancer (CRC) using clinically approved radiopharmaceuticals. I...
This study presents a novel intraoperative in vivo imaging approach which harnessed Cerenkov luminescence (CL) to detect primary and metastatic colorectal cancer (CRC) using clinically approved radiopharmaceuticals. In the mice and swine experiments, the proposed approach effectively improved the effect of CRC surgery. The approach is believed to be promising for utilizing CL in open surgery. Further details can be found in the article by Zeyu Zhang, Yawei Qu, Yu Cao et al. ( e201960152 )
Background: The influence of rising global temperatures on malaria dynamics and distribution remains controversial, especially in central highland regions. We aimed to address this subject by studying the spatiotempor...
Background: The influence of rising global temperatures on malaria dynamics and distribution remains controversial, especially in central highland regions. We aimed to address this subject by studying the spatiotemporal heterogeneity of malaria and the effect of climate change on malaria transmission over 27 years in Hainan, an island province in China. Methods: For this longitudinal cohort study, we used a decades-long dataset of malaria incidence reports from Hainan, China, to investigate the pattern of malaria transmission in Hainan relative to temperature and the incidence at increasing altitudes. Climatic data were obtained from the local meteorological stations in Hainan during 1984–2010 and the WorldClim dataset. A temperature-dependent R0 model and negative binomial generalised linear model were used to decipher the relationship between climate factors and malaria incidence in the tropical region. Findings: Over the past few decades, the annual peak incidence has appeared earlier in the central highland regions but later in low-altitude regions in Hainan, China. Results from the temperature-dependent model showed that these long-term changes of incidence peak timing are linked to rising temperatures (of about 1·5°C). Further, a 1°C increase corresponds to a change in cases of malaria from –5·6% (95% CI –4·5 to –6·6) to –9·2% (95% CI –7·6 to –10·9) from the northern plain regions to the central highland regions during the rainy season. In the dry season, the change in cases would be 4·6% (95% CI 3·7 to 5·5) to 11·9% (95% CI 9·8 to 14·2) from low-altitude areas to high-altitude areas. Interpretation: Our study empirically supports the idea that increasing temperatures can generate opposing effects on malaria dynamics for lowland and highland regions. This should be further investigated and incorporated into future modelling, disease burden calculations, and malaria control, with attention for central highland regions under climate change. Funding: S
The rise of Klebsiella pneumoniae resistant to last-resort antimicrobials poses an urgent threat to global health. The ramR - ramA regulatory system critically influences drug resistance by regulating the AcrAB-TolC e...
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The rise of Klebsiella pneumoniae resistant to last-resort antimicrobials poses an urgent threat to global health. The ramR - ramA regulatory system critically influences drug resistance by regulating the AcrAB-TolC efflux pump, which also plays a crucial role in the pathogenicity of K. pneumoniae . However, the mechanism of the ramR - ramA system on bacteria-host interaction remains unclear. To determine how specific mutations in ramR influence eravacycline (ERV) resistance and their impact on the immune activation capabilities of K. pneumoniae , thereby highlighting potential targets for therapeutic intervention, we performed genetic sequencing to identify mutations in ramR . Then, the CRISPR-Cas9 technology was employed to construct specific ramR mutations into K. pneumoniae , which were then subjected to phenotypic and functional assays in both in vitro and in vivo (mouse models, macrophage, and blood-killing experiment) settings. ramR L58P and F165L genetic alterations disrupt the binding affinity of RamR to the ramA promoter, thereby upregulating the efflux pump expression and increasing ERV minimum inhibitory concentration values up to 64-fold compared to the wild-type. Concurrently, these mutations modulate lipid A structure by increasing 2-hydroxy fatty acid chain abundance. In mouse models, ramR L58P and F165L mutants showed lower bacterial burden in organs (spleen, lung, and kidney) 6 h post-infection, and are fast cleared in 48 h. Furthermore, despite lower intracellular bacterial loads, ramR L58P and F165L mutants induce heightened pro-inflammatory cytokine responses in macrophages and elevate systemic cytokine levels (interleukin [IL]2, IL4, IL6, IL12, interferon-α, and interferon-γ) in human blood co-culture experiments. This study illuminates the critical role of ramR mutations in conferring ERV resistance and enhancing immune responses in K. pneumoniae . The dual impact of these mutations on both antimicrobial resistance and immune activation not on
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