Discovery of novel antibiotics from actinomycetes by integrated metabolomics & genomics approaches

  The explosive increase in infections by pathogens is a major problem in the clinic today. The theme of this thesis was to find novel antibiotics from actinomycetes. Next-generation sequencing revealed that the biosynthetic potential of actinomycetes had been grossly underestimated. In this thesis, different antibiotics-eliciting strategies, including microbial cocultivation, streptomycin-resistant mutation, overexpression of pathway-specific activator, variation of culture conditions, were utilized to enforce fluctuations in the production of bioactive compounds in actinomycetes, after which, NMR-based metabolic profiling was used to facilitate uncovering those elicited molecules. This pipeline allowed the discovery of new antibiotics involving various chemical skeletons, such as 7-prenylisatin, methoxylated isocoumarins, endophenazines, and C-glycosylpyranonaphthoquinones. On the other hand, genome-mining methodology enabled the discovery of a group of endophenasides and leucanicidin in Kitasatospora sp. MBT66, whereby the rhamnosylation of both scaffold are executed by a same promiscuous glycosyltransferase. Last but not least, a novel antibiotic termed lugdunomycin with unprecedented chemical scaffold, as well as a number of new angucycline-type antibiotics, were characterized from Streptomyces sp. QL37. The biosynthetic pathway of lugdunomycin was deciphered by genetic knockout and OSMAC (One Strain MAny Compound) strategy. In summary, this thesis explores an interface of genomics and metabolomics to accelerate new antibiotics discovery.  China Scholarship CouncilMicrobial Biotechnolog

Changes in the soil organic carbon balance on China’s cropland during the last two decades of the 20th century

Agro-ecosystems play an important role in regulating global changes caused by greenhouse gas emissions. Restoration of soil organic carbon (SOC) in agricultural soils can not only improve soil quality but also influence climate change and agronomic productivity. With about half of its land area under agricultural use, China exhibits vast potential for carbon (C) sequestration that needs to be researched. Chinese cropland has experienced SOC change over the past century. The study of SOC dynamics under different bioclimatic conditions and cropping systems can help us to better understand this historical change, current status, the impacts of bioclimatic conditions on SOC and future trends. We used a simulation based on historical statistical data to analyze the C balance of Chinese croplands during the 1980s and 1990s, taking into account soil, climate and agricultural management. Nationwide, 77.6% of the national arable land is considered to be in good condition. Appropriate farm management practices should be adopted to improve the poor C balance of the remaining 22.4% of cropland to promote C sequestration

Impacts of oceanic mixed layer on hurricanes: a simulation experiment with Hurricane Sandy

Author Posting. © American Geophysical Union, 2020. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Oceans 125(11), (2020): e2019JC015851, doi:10.1029/2019JC015851.Influences of the ocean mixed layer (OML) dynamics on intensity, pathway, and landfall of October 2012 Hurricane Sandy were examined through an experiment using the Weather Research and Forecasting (WRF) model. The WRF model was run for two cases with or without coupling to the OML. The OML in the WRF was calculated by an oceanic mixed layer submodel. The initial conditions of the depth and mean water temperature of the OML were specified using Global‐FVCOM and Global‐HYCOM fields. The comparison results between these two cases clearly show that including the OML dynamics enhanced the contribution of vertical mixing to the air‐sea heat flux. When the hurricane moved toward the coast, the local OML rapidly deepened with an increase of storm wind. Intense vertical mixing brought cold water in the deep ocean toward the surface to produce a cold wake underneath the storm, with the lowest sea temperature at the maximum wind zone. This process led to a significant latent heat loss from the ocean within the storm and hence rapid drops of the air temperature and vapor mixing ratio above the sea surface. As a result, the storm was intensified as the central sea level pressure dropped. Improving air pressure simulation with OML tended to reduce the storm size and strengthened the storm intensity and hence provided a better simulation of hurricane pathway and landfall.This work was supported by the MIT Sea Grant College Program through grant 2017‐R/RCM‐49C and 2012‐R/RC‐127, the NSF grants OCE1459096, OCE1332207, and OCE1332666, the NOAA‐funded IOOS NERACOOS program for NECOFS with subcontract numbers NA16NOS0120023 and NERACOOS A002 and A007, and the NOAA‐CINAR Hurricane Sandy fund. The development of the Global‐FVCOM system has been supported by NSF grants OCE1603000. S. Li was supported partially by the oversea Ph.D. fellowship from the China Scholarship Council (No. 1409010025).2021-04-0

Endovascular management of spontaneous axillary artery aneurysm: a case report and review of the literature

INTRODUCTION: Spontaneous atraumatic true axillary artery aneurysm is a relatively unusual disorder. Although most cases are asymptomatic, complications of axillary artery aneurysms may result in acute vascular insufficiency and neurological deficits. Prompt treatment, therefore, should be employed in the management of this condition. To date, the standard treatment for peripheral aneurysms is still surgical resection with end-to-end anastomosis. However, aneurysmectomy and interposition grafting with autologous or artificial vessels are more invasive and time-consuming. The ideal treatment for axillary artery aneurysm should be relatively noninvasive, safe and free of significant complications, cost-effective, cosmetically acceptable, and incur less absence from usual daily activities. Endovascular stent grafts have also been successfully used to treat these aneurysms. Management of select aneurysms using stent grafts has become more prevalent with the developing endoluminal technology. CASE PRESENTATION: We report a case of a spontaneous atraumatic axillary artery aneurysm where the patient was a 48-year-old ethnic Han Chinese woman with a gradually enlarging left axillary pulsatile mass. She was treated with endovascular stent grafts. The postoperative course of the patient was uneventful during the six-month follow-up. CONCLUSIONS: We show that there are significant early advantages with the endovascular management technique versus the conventional operation in the management of axillary artery aneurysm