Automated and miniaturized screening of antibiotic combinations via robotic-printed combinatorial droplet platform

Antimicrobial resistance(AMR)has become a global health crisis in need of novel solutions.To this end,antibiotic combination therapies,which combine multiple antibiotics for treatment,have at-tracted significant attention as a potential approach for combating AMR.To facilitate advances in anti-biotic combination therapies,most notably in investigating antibiotic interactions and identifying synergistic antibiotic combinations however,there remains a need for automated high-throughput plat-forms that can create and examine antibiotic combinations on-demand,at scale,and with minimal reagent consumption.To address these challenges,we have developed a Robotic-Printed Combinatorial Droplet(RoboDrop)platform by integrating a programmable droplet microfuidic device that generates antibiotic combinations in nanoliter droplets in automation,a robotic arm that arranges the droplets in an array,and a camera that images the array of thousands of droplets in parallel.We further implement a resazurin-based bacterial viability assay to accelerate our antibiotic combination testing.As a demonstration,we use RoboDrop to corroborate two pairs of antibiotics with known interactions and subsequently identify a new synergistic combination of cefsulodin,penicillin,and oxacillin against a model E.coli strain.We therefore envision RoboDrop becoming a useful tool to efficiently identify new synergistic antibiotic combinations toward combating AMR.

Long-term outcomes of additional surgery versus non-gastrectomy treatment for early gastric cancer after non-curative endoscopic submucosal dissection: a meta-analysis

Background:Endoscopic resection is increasingly used in the treatment for early gastric cancer(EGC);however,about 15%of endoscopic submucosal dissection(ESD)cases report non-curative resection.The efficacy of different remedial interventions after non-curative ESD for EGC remains controversial.This meta-analysis aimed to compare the long-term outcomes of additional surgery and non-gastrectomy treatment for EGC patients who underwent non-curative ESD.Methods:All relevant studies published up to October 2021 were systematically searched in the PubMed,Web of Science,and Embase databases.The medical subject headings terms"early gastric cancer,""gastrectomy,""endoscopic submucosal dissection,"and their related free keywords were used to search relevant articles without restrictions on regions,publication types,or languages.The Newcastle–Ottawa Quality Assessment Scale was used to evaluate the quality of the included studies.Odds ratios(ORs)with 95%confidence intervals(CIs)of 5-year overall survival(OS),disease-specific survival(DSS),disease-free survival(DFS)and hazard ratios(HRs)with 95%CIs of OS were calculated using a random-or fixed-effects model.Results:This meta-analysis included 17 retrospective cohort studies with 5880 patients,of whom 3167 underwent additional surgery and 2713 underwent non-gastrectomy.We found that patients receiving additional gastrectomy had better 5-year OS(OR=3.63,95%CI=3.05–4.31),DSS(OR=3.22,95%CI=2.22–4.66),and DFS(OR=4.39,95%CI=1.78–10.82)outcomes than those receiving non-gastrectomy treatments.The pooled HR also showed that gastrectomy following non-curative ESD significantly improved OS(HR=0.40,95%CI=0.33–0.48).In addition,elderly patients benefited from additional surgery in consideration of the 5-year OS(HR=0.54,95%CI=0.41–0.72).Conclusions:Compared with non-gastrectomy treatments,additional surgery offered better long-term survival outcomes for patients with EGC who underwent non-curative ESD.

Water level variation characteristics under the impacts of extreme drought and the operation of the Three Gorges Dam

Under the influence of a climate of extreme drought and the Three Gorges Dam (TGD) operation, the water levels in the middle and lower reaches of the Yangtze River in 2006 and 2011 changed significantly compared with those in the extreme drought years of 1978 and 1986. To quantitatively analyze the characteristics of water level variations in 2006 and 2011, a new calculation method was proposed, and the daily water level and discharge from 1955-2016 were collected in this study. The findings are as follows: in 2006 and 2011, the water level in the dry season significantly increased, but that in the flood season obviously decreased compared with the levels in 1978 and 1986. Here, we described this phenomenon as “no low-water-level in dry season, no high-water-level in flood season”. Based on the calculation method, the contributions of climate variability and the Three Gorges Dam operation to water level variations in the middle and lower reaches of the Yangtze River were calculated, and the contributions indicated that climate variability was the main reason for the phenomenon of “no low-water-level in diy season, no high-water-level in flood season” instead of flood peak reduction in the flood season and drought runoff implementation in the dry season, which are both induced by TGD.