Publications by authors named "Lifei Wang"

120 Publications

The ecology of the plastisphere: Microbial composition, function, assembly, and network in the freshwater and seawater ecosystems.

Water Res 2021 Jul 15;202:117428. Epub 2021 Jul 15.

Environment Research Institute, Shandong University, Qingdao 266237, China. Electronic address:

Microplastics provide a unique habitat for microorganisms, forming the plastisphere. Yet the ecology of the plastisphere, including the microbial composition, functions, assembly processes, and interaction networks, needs to be understood. Here, we collected microplastics and their surrounding water samples in freshwater and seawater ecosystems. The bacterial and fungal communities of the plastisphere and the aquatic environment were studied based on 16S and internal transcribed spacer (ITS) high-throughput sequencing. We found that the plastisphere had a distinct microbial community and recruited a noteworthy proportion of unique species compared to the aquatic environment community, potentially altering ecosystem microbial community and causing microbial invasion. Using a random-forest machine-learning model, we identified a group of biomarkers that could best distinguish the plastisphere from the aquatic environment. Significant differences exist in microbial functions between the plastisphere and the aquatic environment, including functions of pathogenicity, compound degradation, as well as functions related to the cycling of carbon, nitrogen, and sulfur. And these functional differences were expressed differently in freshwater and seawater ecosystems. The oxidation-reduction potential, salinity, the concentrations of nitrogen-related ions (NO, NO, and NH), and the concentration of dissolved organic carbon in the surrounding environment drive the variation of the plastisphere. But environmental physicochemical properties explain less of the microbial community variation in the plastisphere than that in the aquatic environment. Niche-based processes govern the assembly of the plastisphere community, while neutral-based processes dominate the community assembly of the aquatic environment. Furthermore, compared to the aquatic environment, the plastisphere has a network of less complexity, more modules, higher modularity, and more competitive links in freshwater ecosystems, but the pattern is reversed in seawater ecosystems. Altogether, the microbial ecology of the new anthropogenic ecosystem-plastisphere-is unique and exerts different effects in freshwater and seawater ecosystems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.watres.2021.117428DOI Listing
July 2021

Conformational transformation of switch domains in GDP/K-Ras induced by G13 mutants: An investigation through Gaussian accelerated molecular dynamics simulations and principal component analysis.

Comput Biol Med 2021 Jul 7;135:104639. Epub 2021 Jul 7.

School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China. Electronic address:

Mutations in K-Ras are involved in a large number of all human cancers, thus, K-Ras is regarded as a promising target for anticancer drug design. Understanding the target roles of K-Ras is important for providing insights on the molecular mechanism underlying the conformational transformation of the switch domains in K-Ras due to mutations. In this study, multiple replica Gaussian accelerated molecular (MR-GaMD) simulations and principal component analysis (PCA) were applied to probe the effect of G13A, G13D and G13I mutations on conformational transformations of the switch domains in GDP-associated K-Ras. The results suggest that G13A, G13D and G13I enhance the structural flexibility of the switch domains, change the correlated motion modes of the switch domains and strengthen the total motion strength of K-Ras compared with the wild-type (WT) K-Ras. Free energy landscape analyses not only show that the switch domains of the GDP-bound inactive K-Ras mainly exist as a closed state but also indicate that mutations evidently alter the free energy profile of K-Ras and affect the conformational transformation of the switch domains between the closed and open states. Analyses of hydrophobic interaction contacts and hydrogen bonding interactions show that the mutations scarcely change the interaction network of GDP with K-Ras and only disturb the interaction of GDP with the switch (SW1). In summary, two newly introduced mutations, G13A and G13I, play similar adjustment roles in the conformational transformations of two switch domains to G13D and are possibly utilized to tune the activity of K-Ras and the binding of guanine nucleotide exchange factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.compbiomed.2021.104639DOI Listing
July 2021

Pulmonary fibrosis and its related factors in discharged patients with new corona virus pneumonia: a cohort study.

Respir Res 2021 Jul 9;22(1):203. Epub 2021 Jul 9.

Shenzhen Key Laboratory of Pathogen and Immunity, National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, Shenzhen Third People's Hospital, Second Hospital Affiliated to Southern University of Science and Technology, No. 29, Bulan Road, Longgang district, Shenzhen, 518112, China.

Background: Thousands of Coronavirus Disease 2019 (COVID-19) patients have been discharged from hospitals Persistent follow-up studies are required to evaluate the prevalence of post-COVID-19 fibrosis.

Methods: This study involves 462 laboratory-confirmed patients with COVID-19 who were admitted to Shenzhen Third People's Hospital from January 11, 2020 to April 26, 2020. A total of 457 patients underwent thin-section chest CT scans during the hospitalization or after discharge to identify the pulmonary lesion. A total of 287 patients were followed up from 90 to 150 days after the onset of the disease, and lung function tests were conducted about three months after the onset. The risk factors affecting the persistence of pulmonary fibrosis were identified through regression analysis and the prediction model of the persistence of pulmonary fibrosis was established.

Results: Parenchymal bands, irregular interfaces, reticulation and traction bronchiectasis were the most common CT features in all COVID-19 patients. During the 0-30, 31-60, 61-90, 91-120 and > 120 days after onset, 86.87%, 74.40%, 79.56%, 68.12% and 62.03% patients developed with pulmonary fibrosis and 4.53%, 19.61%, 18.02%, 38.30% and 48.98% patients reversed pulmonary fibrosis, respectively. It was observed that Age, BMI, Fever, and Highest PCT were predictive factors for sustaining fibrosis even after 90 days from onset. A predictive model of the persistence with pulmonary fibrosis was developed based-on the Logistic Regression method with an accuracy, PPV, NPV, Sensitivity and Specificity of the model of 76%, 71%, 79%, 67%, and 82%, respectively. More than half of the COVID-19 patients revealed abnormal conditions in lung function after 90 days from onset, and the ratio of abnormal lung function did not differ on a statistically significant level between the fibrotic and non-fibrotic groups.

Conclusions: Persistent pulmonary fibrosis was more likely to develop in patients with older age, higher BMI, severe/critical condition, fever, a longer viral clearance time, pre-existing disease and delayed hospitalization. Fibrosis developed in COVID-19 patients could be reversed in about a third of the patients after 120 days from onset. The pulmonary function of less than half of COVID-19 patients could turn to normal condition after three months from onset. An effective prediction model with an average area under the curve (AUC) of 0.84 was established to predict the persistence of pulmonary fibrosis in COVID-19 patients for early diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12931-021-01798-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267229PMC
July 2021

Binding Selectivity of Inhibitors toward Bromodomains BAZ2A and BAZ2B Uncovered by Multiple Short Molecular Dynamics Simulations and MM-GBSA Calculations.

ACS Omega 2021 May 28;6(18):12036-12049. Epub 2021 Apr 28.

School of Science, Shandong Jiaotong University, 5001 Haitang Road, Changqing District, Jinan, Shandong Province 250357, China.

Two Bromodomain-Containing proteins BAZ2A and BAZ2B are responsible for remodeling chromatin and regulating noncoding RNAs. As for our current studies, integration of multiple short molecular dynamics simulations (MSMDSs) with molecular mechanics generalized Born surface area (MM-GBSA) method is adopted for insights into binding selectivity of three small molecules D8Q, D9T and UO1 to BAZ2A against BAZ2B. The calculations of MM-GBSA unveil that selectivity of inhibitors toward BAZ2A and BAZ2B highly depends on the enthalpy changes and the details uncover that D8Q has better selectivity toward BAZ2A than BAZ2B, D9T more favorably bind to BAZ2B than BAZ2A, and UO1 does not show obvious selectivity toward these two proteins. The analysis of interaction network between residues and inhibitors indicates that seven residues are mainly responsible for the selectivity of D8Q, six residues for D9T and four residues provide significant contributions to associations of UO1 with two proteins. Moreover the analysis of interaction network not only reveals warm spots of inhibitor bindings to BAZ2A and BAZ2B but also unveils that common residue pairs, including (W1816, W1887), (P1817, P1888), (F1818, F1889), (V1822, V1893), (N1823, N1894),(L1826, L1897), (V1827, V1898), (F1872, F1943), (N1873, N1944) and (V1879, I1950) belonging to (BAZ2A, BAZ2B), induce mainly binding differences of inhibitors to BAZ2A and BAZ2B. Hence, insights from our current studies offer useful dynamics information relating with conformational alterations and structure-affinity relationship at atomistic levels for novel therapeutic strategies toward BAZ2A and BAZ2B.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsomega.1c00687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154142PMC
May 2021

Observation of the characteristics of the natural course of Bietti crystalline dystrophy by fundus fluorescein angiography.

BMC Ophthalmol 2021 May 28;21(1):239. Epub 2021 May 28.

Beijing Institute of Ophthalmology, Beijing Ophthalmology and Visual Science Key Laboratory, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, 17 Hougou Lane, Chongnei Street, 100005, Beijing, People's Republic of China.

Background: Bietti crystalline dystrophy (BCD) is an autosomal recessive genetic disorder that causes progressive vision loss. Here, 12 patients were followed up for 1-5 years with fundus fluorescein angiography (FFA) to observe BCD disease progression.

Methods: FFA images were collected for 12 patients with BCD who visited our clinic twice or more over a 5-year period. Peripheral venous blood was collected to identify the pathogenic gene related to the clinical phenotype.

Results: We observed two types in FFA images of patients with BCD. Type 1 showed retinal pigment epithelium (RPE) atrophy in the macular area, followed by choriocapillaris atrophy and the subsequent appearance of RPE atrophy appeared at the peripheral retina. Type 2 showed RPE atrophy at the posterior pole and peripheral retina, followed by choriocapillaris atrophy around the macula and along the superior and inferior vascular arcades and the nasal side of the optic disc. The posterior and peripheral lesions of both type 1 and type 2 BCD subsequently extended to the mid-periphery; finally, all the RPEs and choriocapillaris atrophied, exposing the choroid great vessels, but type 2 macular RPE atrophy could last longer.

Conclusions: The characterization of two different types of BCD development provides a better understanding of the phenotype and the progression of the disease for a precise prognosis and prediction of pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12886-021-01999-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161580PMC
May 2021

The decomposition process and nutrient release of invasive plant litter regulated by nutrient enrichment and water level change.

PLoS One 2021 3;16(5):e0250880. Epub 2021 May 3.

Environment Research Institute, Shandong University, Qingdao, China.

Wetlands are vulnerable to plant invasions and the decomposition of invasive plant litter could make impacts on the ecosystem services of wetlands including nutrient cycle and carbon sequestration. However, few studies have explored the effects of nutrient enrichment and water level change on the decomposition of invasive plant litter. In this study, we conducted a control experiment using the litterbag method to compare the decomposition rates and nutrient release in the litter of an invasive plant Alternanthera philoxeroides in three water levels and two nutrient enrichment treatments. This study found that the water level change and nutrient enrichment showed significant effects on the litter decomposition and nutrient dynamic of A. philoxeroides. The increase of water level significantly reduced the decomposition rate and nutrient release of litter in the nutrient control treatment, whereas no clear relationship was observed in the nutrient enrichment treatment, indicating that the effect of water level change on litter decomposition might be affected by nutrient enrichment. At the late stage of decomposition, the increase of phosphorus (P) concentration and the decrease of the ratio of carbon to P suggested that the decomposition of invasive plant litter was limited by P. Our results suggest that controlling P enrichment in water bodies is essential for the management of invasive plant and carbon sequestration of wetlands. In addition, the new index we proposed could provide a basis for quantifying the impact of invasive plant litter decomposition on carbon cycle in wetlands.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250880PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092768PMC
May 2021

Molecular dynamics simulations data of six compounds F3J-BRD4/CBP, EX1-BRD4/CBP, and E2T-BRD4/CBP.

Data Brief 2021 Jun 27;36:107009. Epub 2021 Mar 27.

School of Science, Shandong Jiaotong University, Jinan 250357, China.

The data here described are related to the research article entitled "Molecular dynamics insights into binding selectivity of inhibitors toward BRD4 and CBP" [1]. Bromodomain-containing protein 4 (BRD4) and CREB binding protein (CBP) play important roles in tumorigenesis and development. We performed 200-ns molecular dynamics (MD) simulations on three pairs of inhibitor-BRD4 and inhibitor-CBP complexes to clarify binding selectivity of inhibitors toward BRD4 and CBP. Principal component (PC) analysis was used to probe changes in internal dynamics and conformations of BRD4 and CBP due to inhibitor bindings. Analysis of residue-based free energy decomposition was employed to explore the roles of separate residues in binding selectivity of inhibitors to BRD4 versus CBP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dib.2021.107009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058528PMC
June 2021

The Cytochrome P450 Catalyzing C-S Bond Formation in S-Heterocyclization of Chuangxinmycin Biosynthesis.

Angew Chem Int Ed Engl 2021 07 8;60(28):15399-15404. Epub 2021 Jun 8.

NHC Key Laboratory of Biotechnology of Antibiotics, CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Tiantan Xili, Beijing, 100050, China.

Microbial sulfur-containing secondary metabolites show various biological activities, but the C-S bond-forming in their biosynthetic metabolism has not been thoroughly understood. Here, we present genetic, biochemical and structural characterization of a cytochrome P450 monooxygenase CxnD exhibiting C-S bond forming activity in S-heterocyclization of chuangxinmycin biosynthesis. In vivo and in vitro analyses demonstrated that CxnD generated an indole-fused dihydrothiopyran skeleton from a L-Trp-derived thiol intermediate. Furthermore, X-ray crystal structure of CxnD in complex with a substrate analogue and structure-based mutagenesis revealed intimate details of the substrate binding mode. A radical mechanism initiated by abstraction of the imino hydrogen atom or an electron from indole group of the substrate was proposed for CxnD, which provided valuable insights into the molecular basis for the intra-molecular C(sp )-H thiolation by the P450 in chuangxinmycin biosynthesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.202015814DOI Listing
July 2021

Magnitudes and environmental drivers of greenhouse gas emissions from natural wetlands in China based on unbiased data.

Environ Sci Pollut Res Int 2021 Apr 15. Epub 2021 Apr 15.

Environment Research Institute, Shandong University, Qingdao, 266237, China.

Whether natural wetlands serve as the source or sink of greenhouse gases (GHGs) remains uncertain. Wetlands in China are diverse in type and abundant in quantity and differ greatly in spatial distribution, environmental conditions, and GHG fluxes. However, few studies focused on the differences in GHG emissions from different types of natural wetlands. Here, we adopted strict data collection criteria to create comprehensive and detailed datasets of fluxes of carbon dioxide (CO), methane (CH), and nitrous oxide (NO) from the marsh, coastal, lake, and river wetlands in China, and relevant environmental variables. Our study synthesized 265 field observations on GHGs that lasted at least one year (covering both the growing season and non-growing season) from 109 studies, among which CO measurements using the opaque chamber method were not included for eliminating the influence of absence of photosynthesis on net CO accounting. We found that CH contributed the largest warming effect among the three types of GHGs, and coastal and river wetlands respectively acted as the mitigators and motivators of global warming among the four types of wetlands. Correlation and regression analyses suggested that geographic location, soil moisture and organic carbon, and contents of nitrogen, phosphorus, and dissolved oxygen jointly drove wetland GHG fluxes. The comprehensive global warming potential of Chinese natural wetlands was estimated as 427 Tg CO-equivalents year, which might result from increased wetland drainage, reclamation, and external nutrient inputs. This study highlights the incorporation of the full year-round GHG monitoring data without using opaque chambers to measure CO flux when extrapolating net GHG emissions and gives implications for natural wetland management and global warming mitigation strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-021-13843-4DOI Listing
April 2021

Analysis of pathological changes in the epithelium in COVID-19 patient airways.

ERJ Open Res 2021 Apr 6;7(2). Epub 2021 Apr 6.

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

https://bit.ly/2M2NcdO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/23120541.00690-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898030PMC
April 2021

Thin-section computed tomography findings and longitudinal variations of the residual pulmonary sequelae after discharge in patients with COVID-19: a short-term follow-up study.

Eur Radiol 2021 Mar 11. Epub 2021 Mar 11.

Department of Radiology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, School of Medicine Southern University of Science and Technology, 29 Bulan Road, Longgang District, Shenzhen, 518000, Guangdong, China.

Objectives: This study analyzed and compared CT findings and longitudinal variations after discharge between severe and non-severe coronavirus disease (COVID-19) patients who had residual pulmonary sequelae at pre-discharge.

Methods: A total of 310 patients were included and stratified into severe and non-severe COVID-19 groups. Cross-sectional CT features across different time periods (T0: pre-discharge, T1: 1-4 weeks after discharge, T2: 5-8 weeks after discharge, T3: 9-12 weeks after discharge, T4: > 12 weeks after discharge) were compared, and the longitudinal variations of CT findings were analyzed and compared in both groups.

Results: The cumulative absorption rate of fibrosis-like findings in the severe and non-severe groups at T4 was 24.3% (17/70) and 52.0% (53/102), respectively. In both groups, ground-glass opacity (GGO) with consolidation showed a clear decreasing trend at T1, after which they maintained similar lower levels. The GGO in the severe group showed an increasing trend first at T1 and then decreasing at T4; however, the incidence decreased gradually in the non-severe group. Most fibrosis-like findings showed a tendency to decrease rapidly and then remained stable. Bronchial dilatation in the severe group persisted at an intermediate level.

Conclusions: After discharge, the characteristics and changing trends of pulmonary sequelae caused by COVID-19 were significantly different between the two groups. Pulmonary sequelae were more serious and recovery was slower in patients with severe/critical disease than in patients with moderate disease. A portion of the fibrosis-like findings were completely absorbed in patients with moderate and severe/critical diseases.

Key Points: • Lung sequelae were more serious and recovery was slower in severe/critical COVID-19 patients. • Complete absorption of fibrosis-like findings after a short-term follow-up was observed in at least 17/70 (24.3%) of COVID-19 patients with severe/critical disease and 53/102 (52.0%) of COVID-19 patients with moderate disease. • The most common fibrosis-like findings was a parenchymal band; irregular interface was a nonspecific sign of COVID-19, and the percentage of bronchial dilatation in patients with severe/critical disease remained at a relatively stable medium level (range, 31.6 to 47.8%) at all stages.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-021-07799-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7950423PMC
March 2021

Comparative genomics and transcriptomics analyses provide insights into the high yield and regulatory mechanism of Norvancomycin biosynthesis in Amycolatopsis orientalis NCPC 2-48.

Microb Cell Fact 2021 Feb 2;20(1):28. Epub 2021 Feb 2.

NHC Key Laboratory of Biotechnology of Antibiotics, Beijing, China.

Background: Norvancomycin has been widely used in clinic to treat against MRSA (Methicillin-resistant Staphylococcus aureus) and MRSE (Methicillin-resistant Staphylococcus epidermidis) infections in China. Amycolatopsis orientalis NCPC 2-48, a high yield strain derived from A. orientalis CPCC 200066, has been applied in industrial large-scale production of norvancomycin by North China Pharmaceutical Group. However, the potential high-yield and regulatory mechanism involved in norvancomycin biosynthetic pathway has not yet been addressed.

Results: Here we sequenced and compared the genomes and transcriptomes of A. orientalis CPCC 200066 and NCPC 2-48. These two genomes are extremely similar with an identity of more than 99.9%, and no duplication and structural variation was found in the norvancomycin biosynthetic gene cluster. Comparative transcriptomic analysis indicated that biosynthetic genes of norvancomycin, as well as some primary metabolite pathways for the biosynthetic precursors of norvancomycin were generally upregulated. AoStrR1 and AoLuxR1, two cluster-situated regulatory genes in norvancomycin cluster, were 23.3-fold and 5.8-fold upregulated in the high yield strain at 48 h, respectively. Over-expression of AoStrR1 and AoLuxR1 in CPCC 200066 resulted in an increase of norvancomycin production, indicating their positive roles in norvancomycin biosynthesis. Furthermore, AoStrR1 can regulate the production of norvancomycin by directly interacting with at least 8 promoters of norvancomycin biosynthetic genes or operons.

Conclusion: Our results suggested that the high yield of NCPC 2-48 can be ascribed to increased expression level of norvancomycin biosynthetic genes in its cluster as well as the genes responsible for the supply of its precursors. The norvancomycin biosynthetic genes are presumably regulated by AoStrR1 and AoLuxR1, of them AoStrR1 is possibly the ultimate pathway-specific regulator for the norvancomycin production. These results are helpful for further clarification of the holistic and pathway-specific regulatory mechanism of norvancomycin biosynthesis in the industrial production strain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12934-021-01521-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852140PMC
February 2021

Diverse responses of spring phenology to preseason drought and warming under different biomes in the North China Plain.

Sci Total Environ 2021 Apr 24;766:144437. Epub 2020 Dec 24.

Environment Research Institute, Shandong University, Qingdao 266237, China. Electronic address:

Global-change-type drought, a combination of drought and warmer temperatures, is projected to have severe effects on vegetation growth and ecosystem functions. Spring phenology is an important biological indicator to understand the response of vegetation growth to climate change. However, the differences in the response of spring phenology to global-change-type drought among various vegetation types remain unclear. Here, we extracted the start of growing season (SOS) from NDVI (Normalized Difference Vegetation Index) data using Spline-midpoint, HANTS-Maximum, and Timesat-SG methods in the North China Plain over the period 1982-2015. Then, we investigated the effects of preseason drought on SOS (based on the Standardized Precipitation Evapotranspiration Index, SPEI), and compared responses of SOS to the minimum temperature (T), maximum temperature (T), and mean temperature (T) in different biomes. Results showed a trend of advanced SOS in 81.7% of pixels in the North China Plain, with an average rate of -0.5 days/yr. Negative correlations were found between preseason SPEI and SOS in 72.1% of the study region, and the SOS of grassland showed the least resistance to drought. Interannual variations of SOS were triggered by T more than by T in the North China Plain. Multiple regression analysis exhibited that a 1 °C increase in T would advance SOS by 10.5, 7.6, 2.9, 2.1 days for wheat, other crops, forests, and grasslands, indicating warming displayed greater effects on advancing the SOS of wheat. Considering the coupled effects of preseason drought and warming on spring phenology, future warming would trigger earlier spring green-up, while drought might slow the trend. Besides, nonlinear responses of SOS to preseason SPEI and T along the humidity gradient were discovered. This research provides a new reference for the biome-specific and nonlinear responses in phenology models to promote the understanding of phenology changes, contributing to ecosystem management under future global-change-type drought.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2020.144437DOI Listing
April 2021

Diverse responses of spring phenology to preseason drought and warming under different biomes in the North China Plain.

Sci Total Environ 2021 Apr 24;766:144437. Epub 2020 Dec 24.

Environment Research Institute, Shandong University, Qingdao 266237, China. Electronic address:

Global-change-type drought, a combination of drought and warmer temperatures, is projected to have severe effects on vegetation growth and ecosystem functions. Spring phenology is an important biological indicator to understand the response of vegetation growth to climate change. However, the differences in the response of spring phenology to global-change-type drought among various vegetation types remain unclear. Here, we extracted the start of growing season (SOS) from NDVI (Normalized Difference Vegetation Index) data using Spline-midpoint, HANTS-Maximum, and Timesat-SG methods in the North China Plain over the period 1982-2015. Then, we investigated the effects of preseason drought on SOS (based on the Standardized Precipitation Evapotranspiration Index, SPEI), and compared responses of SOS to the minimum temperature (T), maximum temperature (T), and mean temperature (T) in different biomes. Results showed a trend of advanced SOS in 81.7% of pixels in the North China Plain, with an average rate of -0.5 days/yr. Negative correlations were found between preseason SPEI and SOS in 72.1% of the study region, and the SOS of grassland showed the least resistance to drought. Interannual variations of SOS were triggered by T more than by T in the North China Plain. Multiple regression analysis exhibited that a 1 °C increase in T would advance SOS by 10.5, 7.6, 2.9, 2.1 days for wheat, other crops, forests, and grasslands, indicating warming displayed greater effects on advancing the SOS of wheat. Considering the coupled effects of preseason drought and warming on spring phenology, future warming would trigger earlier spring green-up, while drought might slow the trend. Besides, nonlinear responses of SOS to preseason SPEI and T along the humidity gradient were discovered. This research provides a new reference for the biome-specific and nonlinear responses in phenology models to promote the understanding of phenology changes, contributing to ecosystem management under future global-change-type drought.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2020.144437DOI Listing
April 2021

Development and characterization of rat duodenal organoids for ADME and toxicology applications.

Toxicology 2020 12 24;446:152614. Epub 2020 Oct 24.

Bristol-Myers Squibb R&D, Pharmaceutical Candidate Optimization, Rt. 206 and Province Line Road, Princeton, NJ, 08648, United States. Electronic address:

Many in vitro gastrointestinal models have been developed with the hope that they will continue to improve in their similarity to the organs from which they were isolated. Intestinal organoids isolated from various species are now being used to investigate physiology and pathophysiology. In this study, intestinal stem cells were isolated from adult rat duodenum and culture conditions were optimized to promote the growth, differentiation and development of 3D organoids. We optimized and characterized rat duodenal organoids with light and electron microscopy, immunofluorescence and notably, global mRNA expression. The metabolic capacity of these cultures was investigated using probe substrates for multiple phase I and phase II drug metabolizing enzymes and found to be in line with previous results from intestinal primary cultures and a significant improvement over immortalized cell lines. Over the course of differentiation, the gene expression profiles of the rat duodenal organoids were consistent with expected trends in differentiation to various cell lineages reflecting the duodenum in vivo. Further, incubations of these cultures with naproxen and celecoxib resulted in cytotoxicity consistent with the direct cytotoxic effects of these drugs to duodenum in vivo. Based on these characteristics, the rat duodenal organoids described herein will provide a novel platform for investigating a wide variety of mechanistic questions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tox.2020.152614DOI Listing
December 2020

Clinical characteristics of recovered COVID-19 patients with re-detectable positive RNA test.

Ann Transl Med 2020 Sep;8(17):1084

Institute of Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, China.

Background: The characteristics, significance and potential cause of positive SARS-CoV-2 diagnoses in recovered coronavirus disease 2019 (COVID-19) patients post discharge (re-detectable positive, RP) remained elusive.

Methods: A total of 262 COVID-19 patients discharged from January 23 to February 25, 2020 were enrolled into this study. RP and non-RP (NRP) patients were grouped according to disease severity, and the characterization at re-admission was analyzed. SARS-CoV-2 RNA and plasma antibody levels were measured, and all patients were followed up for at least 14 days, with a cutoff date of March 10, 2020.

Results: A total of 14.5% of RP patients were detected. These patients were characterized as young and displayed mild and moderate conditions compared to NRP patients while no severe patients were RP. RP patients displayed fewer symptoms but similar plasma antibody levels during their hospitalization compared to NRP patients. Upon hospital readmission, these patients showed no obvious symptoms or disease progression. All 21 close contacts of RP patients were tested negative for viral RNA and showed no suspicious symptoms. Eighteen out of 24 of RNA-negative samples detected by the commercial kit were tested positive for viral RNA using a hyper-sensitive method, suggesting that these patients were potential carriers of the virus after recovery from COVID-19.

Conclusions: Our results indicated that young patients, with a mild diagnosis of COVID-19 are more likely to display RP status after discharge. These patients show no obvious symptoms or disease progression upon re-admission. More sensitive RNA detection methods are required to monitor these patients. Our findings provide information and evidence for the management of convalescent COVID-19 patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm-20-5602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575971PMC
September 2020

"Microplastic communities" in different environments: Differences, links, and role of diversity index in source analysis.

Water Res 2021 Jan 26;188:116574. Epub 2020 Oct 26.

Environment Research Institute, Shandong University, Qingdao 266237, China. Electronic address:

Microplastics have been detected in various environments, yet the differences between microplastics in different environments are still largely unknown. Scientists have proposed the concept of the "microplastic cycle," but the evidence for the movement of microplastics between different environments is still scarce. By screening the literature and extracting information, we obtained microplastic data from 709 sampling sites in freshwater, seawater, freshwater sediment, sea sediment, and soil in China. Based on the similarity between microplastics and biological communities, here we propose the concept of a "microplastic community" and examine the differences, links, and diversity of microplastic communities in different environments. Wilcoxon sign-ranks test, Kruskal-Wallis test, and analysis of similarities (ANOSIM) showed that there were significant differences in abundance, proportion of small microplastics, and community composition (shape, color, and polymer types) of microplastics in different environments. The Mantel test showed that there were significant correlations between microplastic community composition in different environments. Network analysis based on community similarity further confirmed the links between microplastic communities. The distance decay models revealed that the links weakened with the increase of geographic distance, suggesting that sampling sites with closed geographical locations had similar pollution sources and more easily to migrate or exchange microplastics. The microplastic diversity integrated index (MDII) was established based on the diversity of microplastic shape, color, and polymer types, and its indication of the number of microplastic pollution sources was verified by the statistical fitting relationship between the number of industrial pollution sources and MDII. Our study provides new insight into the differences and links between microplastics in different environments, which contributes to the microplastic risk assessment and demonstrates the "microplastic cycle." The establishment of the microplastic diversity integrated index could be used in source analysis of microplastics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.watres.2020.116574DOI Listing
January 2021

A promising iPS-based single-cell cloning strategy revealing signatures of somatic mutations in heterogeneous normal cells.

Comput Struct Biotechnol J 2020 3;18:2326-2335. Epub 2020 Sep 3.

Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation, Beijing 100101, China.

Single-cell genomics has advanced rapidly as trace-DNA amplification technologies evolved. However, current technologies are subject to a variety of pitfalls such as contamination, uneven genomic coverage, and amplification errors. Even for the "golden" strategy of single stem cell-derived clonal formation, high-fidelity amplification is applicable merely to single stem cells. It's still challenging to accurately define somatic mutations of a single cell in various cell types. Herein, we provided evidence, for the first time, to prove that induced pluripotent stem cells (iPS cells or iPSC), being a single somatic cell-derived clone, are recording almost identical (>90%) mutational profile of the initial cell progenitor. This finding demonstrates iPS technique, applicable to any cell type, can be utilized as a cell cloning strategy favorable for single-cell genomic amplification. This novel strategy is not limited by cell-type constraints or amplification artifacts, and thus enables our detailed investigation on the characteristics of somatic mutations in heterogeneous normal cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.csbj.2020.08.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493045PMC
September 2020

MAL2 drives immune evasion in breast cancer by suppressing tumor antigen presentation.

J Clin Invest 2021 Jan;131(1)

Department of Medical and Molecular Genetics.

Immune evasion is a pivotal event in tumor progression. To eliminate human cancer cells, current immune checkpoint therapy is set to boost CD8+ T cell-mediated cytotoxicity. However, this action is eventually dependent on the efficient recognition of tumor-specific antigens via T cell receptors. One primary mechanism by which tumor cells evade immune surveillance is to downregulate their antigen presentation. Little progress has been made toward harnessing potential therapeutic targets for enhancing antigen presentation on the tumor cell. Here, we identified MAL2 as a key player that determines the turnover of the antigen-loaded MHC-I complex and reduces the antigen presentation on tumor cells. MAL2 promotes the endocytosis of tumor antigens via direct interaction with the MHC-I complex and endosome-associated RAB proteins. In preclinical models, depletion of MAL2 in breast tumor cells profoundly enhanced the cytotoxicity of tumor-infiltrating CD8+ T cells and suppressed breast tumor growth, suggesting that MAL2 is a potential therapeutic target for breast cancer immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/JCI140837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773365PMC
January 2021

A combined method for the source apportionment of sediment organic carbon in rivers.

Sci Total Environ 2021 Jan 21;752:141840. Epub 2020 Aug 21.

Environment Research Institute, Shandong University, Qingdao 266237, China. Electronic address:

Organic carbon sources apportionment in river sediments is crucial to the output management of organic carbon. We conducted a source apportionment of sediment organic carbon in four rivers in Shaanxi Province, China, with a novel method that combined environmental scanning electron microscopy and energy dispersive X-ray spectrometry (ESEM-EDAX), principal component analysis (PCA), 16S rRNA sequencing, microbial community metabolic prediction, and positive matrix factorization (PMF). According to the ESEM-EDAX results, the sources of light fraction organic carbon (LFOC) were the vegetation residues and the organic carbon adsorbed on them; and the source of heavy fraction organic carbon (HFOC) was organic carbon wrapped in particles. Moreover, 16S rRNA sequencing results of LFOC and HFOC concerning microbes demonstrated that LFOC was mainly composed of carbohydrate, cellulose, and alky-aromatic compounds, and that carbohydrate with high molecular weight might be a part of HFOC. Based on the results of microbial community metabolic prediction, PCA, and PMF, we found dissolved organic carbon (DOC) was mainly from lipopolysaccharide biosynthesis, apoptosis, and decomposition of carboxylic acids. And it might be mainly composed of lipopolysaccharide, carbohydrates, and organic acid with low molecular. To reflect the appearance of a specific DOC type, three biomarkers were proposed based on the microbial relative abundance and specificity. This research proposed a new method to trace the sources of organic carbon and established microbial biomarkers for the appearance of specific DOC, which would promote the understanding of organic carbon sources into microbes. Thus, this research provides new perspectives in the source apportionment and the life cycle of organic carbon in rivers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2020.141840DOI Listing
January 2021

Effects of heavy metals on microbial communities in sediments and establishment of bioindicators based on microbial taxa and function for environmental monitoring and management.

Sci Total Environ 2020 Dec 12;749:141555. Epub 2020 Aug 12.

Environment Research Institute, Shandong University, Qingdao 266237, China. Electronic address:

Heavy metals have always been a research hotspot due to their persistence, hazard and bioaccumulation. Microorganisms are highly sensitive to heavy metal pollution and play an important role in the material cycling and energy flow of the ecosystem. In order to further explore the influence of heavy metals on the diversity, composition, and function of microbial communities in the wetland sediment ecosystem, and to find suitable indicators to reflect heavy metal pollution status, we collected sediments from Huangjinxia nature reserve and determined the physicochemical properties, heavy metal (Cu, Cr, Ni, Pb, Zn, and Mn) concentrations, and microbial information. We found that: the contamination status of the study area stood at a moderate level evaluated by the pollution load index (PLI); heavy metals explained more of microbial community variation than the sediment physicochemical properties; in particular, Cr and Mn negatively affected microbial α-diversity; heavy metals significantly affected the structure of microbial communities, elements Cr, Pb, and Zn showed uniformly negative associations with the relative abundance of bacteria Nitrospirae (including class Nitrospira and order Nitrospirales), Bacteroidetes (including class Bacteroidia), and Verrucomicrobia; moreover, heavy metals affected predicted functions of microbial communities, including metabolic functions, genetic information processes, and functions related to the carbon cycle and the nitrogen cycle. Based on the relative abundance of sensitive microbial taxa and predicted functions, bioindicators [Bacteroidia], 1/[Nitrospira], 1/[Nitrification], and 1/[Aerobic nitrite oxidation] were established to reflect and predict the contamination status of heavy metals in sediments. Our in-depth research on the effects of heavy metals on microorganisms and the establishment of bioindicators provide references and new perspectives for environmental monitoring and management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2020.141555DOI Listing
December 2020

Absorption and Disposition of Coproporphyrin I (CPI) in Cynomolgus Monkeys and Mice: Pharmacokinetic Evidence to Support the Use of CPI to Inform the Potential for Organic Anion-Transporting Polypeptide Inhibition.

Drug Metab Dispos 2020 08 1;48(8):724-734. Epub 2020 Jun 1.

Departments of Metabolism and Pharmacokinetics (X.G., L.W., J.G., R.M.F., Y.L., M.S., H.S.) and Radiochemistry (Y.T., Y.H.), Bristol Myers Squibb Company, Princeton, New Jersey

Despite a recent expansion in the recognition of the potential utility of coproporphyrin (CP) as an endogenous biomarker of organic anion-transporting polypeptide (OATP) 1B activity, there have been few detailed studies of CP's pharmacokinetic behavior and an overall poor understanding of its pharmacokinetic fate from tissues and excretion. Here, we describe the pharmacokinetics of octadeuterium-labeled coproporphyrin I (CPI-d8) in cynomolgus monkeys following oral and intravenous administration. CPI-d8 has a half-life and bioavailability of 7.6 hours and 3.2%, respectively. Cynomolgus monkeys received oral cyclosporin A (CsA) at 4, 20, and 100 mg/kg which yielded maximum blood concentrations ( ) and area under the plasma concentration-time curve (AUC) values of 0.19, 2.5, and 3.8 µM, and 2.7, 10.5, and 26.6 µM·h, respectively. The apparent CsA-dose dependent increase in the AUC ratio of CPI-d8 (1.8, 6.2, and 10.5), CPI (1.1, 1.4, and 4.4), and CPIII (1.1, 1.8, and 4.6) at 4, 20, and 100 mg, respectively. In contrast, the plasma concentrations of CPI and CPIII were generally not affected by intravenous administration of the renal organic anion and cation transporter inhibitors (probenecid and pyrimethamine, respectively). In addition, tritium-labeled coproporphyrin I ([H]CPI) showed specific and rapid distribution to the liver, intestine, and kidney after an intravenous dose in mice using quantitative whole-body autoradiography. Rifampin markedly reduced the liver and intestinal uptake of [H]CPI while increasing the kidney uptake. Taken together, these results suggest that hepatic OATP considerably affects the disposition of CPI in animal models, indicating CPI is a sensitive and selective endogenous biomarker of OATP inhibition. SIGNIFICANCE STATEMENT: This study demonstrated that coproporphyrin I (CPI) has favorable oral absorption, distribution, and elimination profiles in monkeys and mice as an endogenous biomarker. It also demonstrated its sensitivity and selectivity as a probe of organic anion-transporting polypeptide (OATP) 1B activity. The study reports, for the first time, in vivo pharmacokinetics, tissue distribution, sensitivity, and selectivity of CPI as an OATP1B endogenous biomarker in animals. The data provide preclinical support for exploration of its utility as a sensitive and selective circulating OATP biomarker in humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1124/dmd.120.090670DOI Listing
August 2020

Oyster copper levels in the northern South China Sea from 1989 to 2015: spatiotemporal trend detection and human health implications.

Environ Sci Pollut Res Int 2020 Oct 6;27(30):37384-37394. Epub 2020 May 6.

Key Laboratory of Fishery Ecology and Environment, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, 510300, Guangdong, China.

Coastal heavy metal pollution has become an important topic for seafood safety and marine environmental protection. Unlike toxic heavy metals such as cadmium or chromium, copper is essential for oysters' growth but can inhibit their immune response to exotic stress when going above normal levels. Oysters with high copper levels can easily accumulate and transfer abnormal amounts of copper to upper trophic levels, and generate health risks for humans. This study investigated the spatiotemporal variability and health risk of copper levels in cultured oysters (Crassostrea rivularis) sampled from 23 harbors, bays, or estuaries along the northern South China Sea during 1989-2015. Overall, oyster copper concentrations in the study area ranged from 0.9 to 1897.0 μg/g wet weight with a mean of 210.0 (± 143.6) μg/g and a median of 89.3 μg/g. Although oyster copper levels in the southern China provinces of Guangdong, Guangxi, and Hainan showed an overall decrease during 1989-2015, they stayed relatively low since 1996 and increased slightly after 2010. Oyster copper levels in Guangdong were significantly higher than in Hainan and Guangxi. In Guangdong, oyster copper levels were highest in the Pearl River Estuary, followed by west Guangdong and east Guangdong. The health risk of copper exposure through oyster consumption increased in 2011-2015 compared with in 2006-2010. It is recommended that the human daily intake of cultured oysters in the study area should be reduced by half to minimize copper exposure. This study suggested that copper is one of the most important heavy metal contaminants in coastal and estuarine ecosystems of the northern South China Sea.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-020-09106-3DOI Listing
October 2020

Inefficient thermogenic mitochondrial respiration due to futile proton leak in a mouse model of fragile X syndrome.

FASEB J 2020 06 20;34(6):7404-7426. Epub 2020 Apr 20.

Department of Anesthesiology, Columbia University Medical Center, New York, NY, USA.

Fragile X syndrome (FXS) is the leading known inherited intellectual disability and the most common genetic cause of autism. The full mutation results in transcriptional silencing of the Fmr1 gene and loss of fragile X mental retardation protein (FMRP) expression. Defects in neuroenergetic capacity are known to cause a variety of neurodevelopmental disorders. Thus, we explored the integrity of forebrain mitochondria in Fmr1 knockout mice during the peak of synaptogenesis. We found inefficient thermogenic respiration due to futile proton leak in Fmr1 KO mitochondria caused by coenzyme Q (CoQ) deficiency and an open cyclosporine-sensitive channel. Repletion of mitochondrial CoQ within the Fmr1 KO forebrain closed the channel, blocked the pathological proton leak, restored rates of protein synthesis during synaptogenesis, and normalized the key phenotypic features later in life. The findings demonstrate that FMRP deficiency results in inefficient oxidative phosphorylation during the neurodevelopment and suggest that dysfunctional mitochondria may contribute to the FXS phenotype.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1096/fj.202000283RRDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692004PMC
June 2020

Clinical efficacy and prognostic factors of CT-guided I brachytherapy for the palliative treatment of retroperitoneal metastatic lymph nodes.

Cancer Imaging 2020 Apr 6;20(1):25. Epub 2020 Apr 6.

Sun Yat-sen University Cancer Center, 651 Dongfeng Road, East, Guangzhou, 510060, China.

Background: Due to the unique anatomical location of retroperitoneal metastatic lymph nodes, current treatment options are limited. This study was designed to explore the clinical efficacy and prognostic factors of CT-guided I brachytherapy for the treatment of retroperitoneal metastatic lymph nodes.

Methods: We retrospectively evaluated 92 patients received I brachytherapy for retroperitoneal metastatic lymph nodes. A layered Cox proportional hazards model was established to filter out the independent factors affecting local tumor progression-free survival (LTPFS).

Results: The median LTPFS was 8 months. Metastatic lymph node with uniform density (p-0.009), clear boundaries (p-0.011), regular morphology (P < 0.001), and < 3 organs at risk of metastasis (p-0.020) were associated with better LTPFS. Necrotic lymph nodes (p < 0.001), fusion (p-0.003), and invasion of vessels visible on images (p < 0.001) were associated with poor LTPFS. Puncture path through abdominal wall or paravertebral approach were also associated with better LTPFS than a hepatic approach (P < 0.05). A maximum diameter ≤ 3 cm (P-0.031) or 3-5 cm (P-0.018) were also associated with significantly better LTPFS than a maximum diameter ≥ 5 cm. The Cox proportional hazards model suggested that lymph nodes invaded the large vessels visible on images, maximum diameter and puncture path were independent risk factors for LTPFS.

Conclusion: CT-guided I brachytherapy is an optional palliative treatment modality for retroperitoneal metastatic lymph nodes, which can provide high local control without severe complications. Better preoperative planning, intraoperative implementation, better choice of puncture path, and selection of appropriate tumor size are important factors that can improve the clinical efficacy of I brachytherapy for retroperitoneal metastatic lymph nodes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40644-020-00299-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7137200PMC
April 2020

Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury.

Sci China Life Sci 2020 03 9;63(3):364-374. Epub 2020 Feb 9.

Shenzhen Key Laboratory of Pathogen and Immunity, National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, Shenzhen Third People's Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, 518112, China.

The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan, Hubei province, and rapidly spread to many provinces in China as well as other countries. Here we report the epidemiological, clinical, laboratory, and radiological characteristics, as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen, China. All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS). The most common laboratory abnormalities were hypoalbuminemia, lymphopenia, decreased percentage of lymphocytes (LYM) and neutrophils (NEU), elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased CD8 count. The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity. ALB, LYM, LYM (%), LDH, NEU (%), and CRP were highly correlated to the acute lung injury. Age, viral load, lung injury score, and blood biochemistry indexes, albumin (ALB), CRP, LDH, LYM (%), LYM, and NEU (%), may be predictors of disease severity. Moreover, the Angiotensin II level in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury. Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11427-020-1643-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7088566PMC
March 2020

Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury.

Sci China Life Sci 2020 03 9;63(3):364-374. Epub 2020 Feb 9.

Shenzhen Key Laboratory of Pathogen and Immunity, National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, Shenzhen Third People's Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, 518112, China.

The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan, Hubei province, and rapidly spread to many provinces in China as well as other countries. Here we report the epidemiological, clinical, laboratory, and radiological characteristics, as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen, China. All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS). The most common laboratory abnormalities were hypoalbuminemia, lymphopenia, decreased percentage of lymphocytes (LYM) and neutrophils (NEU), elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased CD8 count. The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity. ALB, LYM, LYM (%), LDH, NEU (%), and CRP were highly correlated to the acute lung injury. Age, viral load, lung injury score, and blood biochemistry indexes, albumin (ALB), CRP, LDH, LYM (%), LYM, and NEU (%), may be predictors of disease severity. Moreover, the Angiotensin II level in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury. Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11427-020-1643-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7088566PMC
March 2020

Comparison of foveal avascular zone and retinal vascular density in healthy Chinese and Caucasian adults.

Acta Ophthalmol 2020 Jun 26;98(4):e464-e469. Epub 2019 Nov 26.

Ophthalmology Department, Railway Hospital, Katowice, Poland.

Purpose: The aim of this study was to measure and compare the retinal vascular parameters and foveal avascular zone (FAZ) in Chinese and Caucasian populations by using optical coherence tomography angiography (OCT-A).

Methods: Fifty-one eyes of Han Chinese and 43 eyes of Caucasians were retrospectively included in our study. The measurements were acquired using Zeiss Cirrus 5000, with the same software version 10 in Poland and China.

Results: The size of the FAZ was 0.33 ± 0.012 and 0.28 ± 0.014 mm (p = 0.0289) and the diameter was 2.43 ± 0.06 and 2.18 ± 0.07 mm (p = 0.0057) for Chinese and Caucasian populations, respectively. However, no differences were observed in circularities between the populations. The full Early Treatment of Diabetic Retinopathy Study (ETDRS) vessel length density was significantly different for Chinese (17.05 ± 0.24 mm/mm ) and Caucasian (16.08 ± 0.43 mm/mm ) populations. In addition, the outer ETDRS vessel length density was significantly different for Chinese (16.43 ± 0.42 mm/mm ) and Caucasian (17.47 ± 0.24 mm/mm ) populations, but the central 7.33 ± 1.68 versus 9.32 ± 1.54 mm/mm for the Caucasian and Chinese and inner 16.14 ± 0.52 for Caucasian and 16.93 ± 0.27 mm/mm for Chinese subjects density was not. A significant yet weak positive correlation between FAZ and vessel density was observed (r = 0.216). Furthermore, no significant intersexual differences were observed in study parameters.

Conclusion: The Chinese population had larger FAZ with higher vessel length density in the superficial layers of the retina than the Caucasian population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aos.14316DOI Listing
June 2020

Exploring novel herbicidin analogues by transcriptional regulator overexpression and MS/MS molecular networking.

Microb Cell Fact 2019 Oct 15;18(1):175. Epub 2019 Oct 15.

NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Tiantan Xili, Beijing, 100050, China.

Background: Herbicidin F has an undecose tricyclic furano-pyrano-pyran structure with post-decorations. It was detected from Streptomyces mobaraensis US-43 fermentation broth as a trace component by HPLC-MS analysis. As herbicidins exhibit herbicidal, antibacterial, antifungal and antiparasitic activities, we are attracted to explore more analogues for further development.

Results: The genome of S. mobaraensis US-43 was sequenced and a herbicidin biosynthetic gene cluster (hcd) was localized. The cluster contains structural genes, one transporter and three potential transcription regulatory genes. Overexpression of the three regulators respectively showed that only hcdR2 overexpression significantly improved the production of herbicidin F, and obviously increased the transcripts of 7 structural genes as well as the transporter gene. After performing homology searches using BLASTP in the GenBank database, 14 hcd-like clusters were found with a cluster-situated hcdR2 homologue. These HcdR2 orthologues showed overall structural similarity, especially in the C-terminal DNA binding domain. Based on bioinformatics analysis, a 21-bp consensus binding motif of HcdR2 was detected within 30 promoter regions in these genome-mined clusters. EMSA results verified that HcdR2 bound to the predicted consensus sequence. Additionally, we employed molecular networking to explore novel herbicidin analogues in hcdR2 overexpression strain. As a result, ten herbicidin analogues including six new compounds were identified based on MS/MS fragments. Herbicidin O was further purified and confirmed by H NMR spectrum.

Conclusions: A herbicidin biosynthetic gene cluster (hcd) was identified in S. mobaraensis US-43. HcdR2, a member of LuxR family, was identified as the pathway-specific positive regulator, and the production of herbicidin F was dramatically increased by overexpression of hcdR2. Combined with molecular networking, ten herbicidin congeners including six novel herbicidin analogues were picked out from the secondary metabolites of hcdR2 overexpression strain. The orthologues of herbicidin F pathway-specific regulator HcdR2 were present in most of the genome-mined homologous biosynthetic gene clusters, which possessed at least one consensus binding motif with LuxR family characteristic. These results indicated that the combination of overexpression of hcdR2 orthologous regulator and molecular networking might be an effective way to exploit the "cryptic" herbicidin-related biosynthetic gene clusters for discovery of novel herbicidin analogues.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12934-019-1225-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6794829PMC
October 2019

Draft Genome Sequence of Teicoplanin-Producing Strain Actinoplanes teichomyceticus CPCC 203265.

Microbiol Resour Announc 2019 Oct 10;8(41). Epub 2019 Oct 10.

NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

We report here the draft genome sequence of CPCC 203265, a producer of glycopeptide antibiotic teicoplanin, which has significant inhibitory activity against multidrug-resistant Gram-positive pathogens. The draft genome size is 8 Mb, with a G+C content of 72.8%, and its sequence will facilitate the genome exploration of novel secondary metabolites.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/MRA.01091-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787327PMC
October 2019
-->