Publications by authors named "Xiaohui Ma"

164 Publications

Intestinal microbiota and antibiotic-associated acute gastrointestinal injury in sepsis mice.

Aging (Albany NY) 2021 Mar 26;13. Epub 2021 Mar 26.

Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin 150001, Heilongjiang, China.

Background: To investigate the changes of intestinal microbiota and metabolites in sepsis mice with acute gastrointestinal injury before and after the use of antibiotics, and to explore the possible effects of these changes on the body.

Methods: Twenty-four 6-8-w-old SPF-grade C57BL/6J male mice were selected, and the mice were randomly divided into three groups. The mice were treated by tail vein injection for 3 days. The intestinal motility of mice after administration was detected. The mice feces were collected for 16S rRNA and Untargeted metabonomics detection.

Results: The use of antibiotics in sepsis mice can change the composition of intestinal microbiota and metabolites. LD3, AD3 and LAD3 samples had significant differences in bacterial species. was the species with a significant difference in LAD3. In addition, we found that the composition of those intestinal microbiota were correlated with changes in intestinal motility. The untargeted metabolomics analysis showed that the fecal metabolites of LD3 and LAD3 samples were significantly different. In addition to the basic metabolites, Benzoic acid and 4-Hydroxybenzoic acid were also found, and was associated with them.

Conclusions: The use of antibiotics in sepsis mice can lead to changes in the intestinal microbiota and metabolite levels, which may be related to the severity of acute gastrointestinal injury in sepsis mice. Inhibiting in the intestine and using Benzoic acid and 4-Hydroxybenzoic acid as a marker for the production of may reduce the inflammatory degree of acute gastrointestinal injury in sepsis.
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http://dx.doi.org/10.18632/aging.202768DOI Listing
March 2021

Effects of Sevoflurane Inhalation Anesthesia on the Intestinal Microbiome in Mice.

Front Cell Infect Microbiol 2021 18;11:633527. Epub 2021 Mar 18.

Department of Critical Care Medicine, Harbin Medical University Cancer Hospital, Harbin, China.

In recent years, more and more attention has been paid to intestinal microbiome. Almost all operations will go through the anesthesia process, but it is not clear whether the intervention of anesthesia alone will affect the change in the intestinal microbiome. The purpose of this study was to verify the effect of sevoflurane inhalation anesthesia on the intestinal microbiome. The animal in the experimental group was used to provide sevoflurane inhalation anesthesia for 4 hours. The control group was not intervened. The feces of the experimental group and the control group were collected on the 1st, 3rd, 7th and 14th days after anesthesia. Sevoflurane inhalation anesthesia will cause changes in the intestinal microbiome of mice. It appears on the 1st day after anesthesia and is most obvious on the 7th day. The specific manifestation is that the abundance of microbiome and the diversity of the microbiome is reduced. At the same time, Untargeted metabonomics showed that compared with the control group, the experimental group had more increased metabolites related to the different microbiome, among which 5-methylthioadenosine was related to the central nervous system. Subsequently, the intestinal microbiome diversity of mice showed a trend of recovery on the 14th day. At the genus level, the fecal samples obtained on the 14th day after anesthesia exhibited significantly increased abundances of Bacteroides, Alloprevotella, and Akkermansia and significantly decreased abundances of Lactobacillus compared with the samples obtained on the 1st day after anesthesia. However, the abundance of differential bacteria did not recover with the changing trend of diversity. Therefore, we believe that sevoflurane inhalation anesthesia is associated with changes in the internal microbiome and metabolites, and this change may be completed through the brain-gut axis, while sevoflurane inhalation anesthesia may change the intestinal microbiome for as long as 14 days or longer.
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http://dx.doi.org/10.3389/fcimb.2021.633527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012717PMC
March 2021

All-normal-dispersion dissipative soliton fiber laser using an offset-splicing graded-index-multimode-fiber-based saturable absorber.

Appl Opt 2021 Feb;60(4):923-928

All-normal-dispersion (ANDi) dissipative soliton mode-locking is realized based on nonlinear multimode interference (NMI), which is implemented by offset-splicing three pieces of graded-index multimode fibers (GIMFs) and acts as a saturable absorber. The higher-order modes can be excited by offset-splicing GIMFs (OS-GIMFs), which eliminates adding the step multimode fiber (SIMF) into the resonant cavity and the precise length requirement of the SIMF. In the experiment, the stable dissipative soliton mode-locking at 1030 nm can be obtained with the pulse width of 7.3 ps and the repetition rate of 20.52 MHz, and the bandwidth is 6.98 nm. The maximum output is 3.2 mW with the pump power of 257 mW. The OS-GIMFs can significantly improve the saturated absorption and can easily realize dissipative soliton mode-locking in ANDi regions, which makes it attractive in ultrafast photonics.
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http://dx.doi.org/10.1364/AO.413601DOI Listing
February 2021

Hyocholic acid species as novel biomarkers for metabolic disorders.

Nat Commun 2021 03 5;12(1):1487. Epub 2021 Mar 5.

Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus and Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Hyocholic acid (HCA) is a major bile acid (BA) species in the BA pool of pigs, a species known for its exceptional resistance to spontaneous development of diabetic phenotypes. HCA and its derivatives are also present in human blood and urine. We investigate whether human HCA profiles can predict the development of metabolic disorders. We find in the first cohort (n = 1107) that both obesity and diabetes are associated with lower serum concentrations of HCA species. A separate cohort study (n = 91) validates this finding and further reveals that individuals with pre-diabetes are associated with lower levels of HCA species in feces. Serum HCA levels increase in the patients after gastric bypass surgery (n = 38) and can predict the remission of diabetes two years after surgery. The results are replicated in two independent, prospective cohorts (n = 132 and n = 207), where serum HCA species are found to be strong predictors for metabolic disorders in 5 and 10 years, respectively. These findings underscore the association of HCA species with diabetes, and demonstrate the feasibility of using HCA profiles to assess the future risk of developing metabolic abnormalities.
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http://dx.doi.org/10.1038/s41467-021-21744-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935989PMC
March 2021

Insights into the mechanism regulating the differential expression of the P28-OMP outer membrane proteins in obligatory intracellular pathogen .

Emerg Microbes Infect 2021 Dec;10(1):461-471

Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, People's Republic of China.

causes human monocytic ehrlichiosis (HME), which is one of the most prevalent, life-threatening emerging infectious zoonoses. The life cycle of includes ticks and mammals, in which proteins are expressed differentially contributing to bacterial survival and infection. Among the P28-OMP outer membrane proteins, OMP-1B and P28 are predominantly expressed in tick cells and mammalian macrophages, respectively. The mechanisms regulating this differential expression have not been comprehensively studied. Here, we demonstrate that the transcriptional regulators EcxR and Tr1 regulate the differential expression of and in Recombinant Tr1 bound to the promoters of and and transactivated and promoter-EGFP fusion constructs in . The consensus sequence of Tr1 binding motifs was A/TATA as determined with DNase I footprint assay. Tr1 showed a higher affinity towards the promoter than the promoter as determined with surface plasmon resonance. EcxR activated the expression in response to a temperature decrease. At 37°C low level of Tr1 activated the expression. At 25°C high level of Tr1 activated the expression, while repressing the expression by binding to an additional site upstream of the gene. Our data provide insights into a novel mechanism mediated by Tr1 regulating differential gene expression, which may aid in the development of new therapeutics for HME.
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http://dx.doi.org/10.1080/22221751.2021.1899054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971322PMC
December 2021

Ocean fronts and eddies force atmospheric rivers and heavy precipitation in western North America.

Nat Commun 2021 02 24;12(1):1268. Epub 2021 Feb 24.

Department of Geological and Atmospheric Sciences, Iowa State University, Ames, IA, USA.

Atmospheric rivers (ARs) are responsible for over 90% of poleward water vapor transport in the mid-latitudes and can produce extreme precipitation when making landfall. However, weather and climate models still have difficulty simulating and predicting landfalling ARs and associated extreme precipitation, highlighting the need to better understand AR dynamics. Here, using high-resolution climate models and observations, we demonstrate that mesoscale sea-surface temperature (SST) anomalies along the Kuroshio Extension can exert a remote influence on landfalling ARs and related heavy precipitation along the west coast of North America. Inclusion of mesoscale SST forcing in the simulations results in approximately a 40% increase in landfalling ARs and up to a 30% increase in heavy precipitation in mountainous regions and this remote impact occurs on two-week time scales. The asymmetrical response of the atmosphere to warm vs. cold mesoscale SSTs over the eddy-rich Kuroshio Extension region is proposed as a forcing mechanism that results in a net increase of moisture flux above the planetary boundary layer, prompting AR genesis via enhancing moisture transport into extratropical cyclones in the presence of mesoscale SST forcing.
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http://dx.doi.org/10.1038/s41467-021-21504-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904778PMC
February 2021

Expansion within the CYP71D subfamily drives the heterocyclization of tanshinones synthesis in Salvia miltiorrhiza.

Nat Commun 2021 01 29;12(1):685. Epub 2021 Jan 29.

State Key Laboratory Breeding Base of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.

Tanshinones are the bioactive nor-diterpenoid constituents of the Chinese medicinal herb Danshen (Salvia miltiorrhiza). These groups of chemicals have the characteristic furan D-ring, which differentiates them from the phenolic abietane-type diterpenoids frequently found in the Lamiaceae family. However, how the 14,16-epoxy is formed has not been elucidated. Here, we report an improved genome assembly of Danshen using a highly homozygous genotype. We identify a cytochrome P450 (CYP71D) tandem gene array through gene expansion analysis. We show that CYP71D373 and CYP71D375 catalyze hydroxylation at carbon-16 (C16) and 14,16-ether (hetero)cyclization to form the D-ring, whereas CYP71D411 catalyzes upstream hydroxylation at C20. In addition, we discover a large biosynthetic gene cluster associated with tanshinone production. Collinearity analysis indicates a more specific origin of tanshinones in Salvia genus. It illustrates the evolutionary origin of abietane-type diterpenoids and those with a furan D-ring in Lamiaceae.
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http://dx.doi.org/10.1038/s41467-021-20959-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846762PMC
January 2021

A theoretical study of hydrogen-bonded molecular clusters of sulfuric acid and organic acids with amides.

J Environ Sci (China) 2021 Feb 16;100:328-339. Epub 2020 Aug 16.

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

Amides, a series of significant atmospheric nitrogen-containing volatile organic compounds (VOCs), can participate in new particle formation (NPF) throught interacting with sulfuric acid (SA) and organic acids. In this study, we investigated the molecular interactions of formamide (FA), acetamide (AA), N-methylformamide (MF), propanamide (PA), N-methylacetamide (MA), and N,N-dimethylformamide (DMF) with SA, acetic acid (HAC), propanoic acid (PAC), oxalic acid (OA), and malonic acid (MOA). Global minimum of clusters were obtained through the association of the artificial bee colony (ABC) algorithm and density functional theory (DFT) calculations. The conformational analysis, thermochemical analysis, frequency analysis, and topological analysis were conducted to determine the interactions of hydrogen-bonded molecular clusters. The heterodimers formed a hepta or octa membered ring through four different types of hydrogen bonds, and the strength of the bonds are ranked in the following order: SOH•••O > COH•••O > NH•••O > CH•••O. We also evaluated the stability of the clusters and found that the stabilization effect of amides with SA is weaker than that of amines with SA but stronger than that of ammonia (NH) with SA in the dimer formation of nucleation process. Additionally, the nucleation capacity of SA with amides is greater than that of organic acids with amides.
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http://dx.doi.org/10.1016/j.jes.2020.07.022DOI Listing
February 2021

Anti-Adipogenic Effect of Theabrownin Is Mediated by Bile Acid Alternative Synthesis via Gut Microbiota Remodeling.

Metabolites 2020 Nov 23;10(11). Epub 2020 Nov 23.

Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.

Theabrownin is one of the most bioactive compounds in Pu-erh tea. Our previous study revealed that the hypocholesterolemic effect of theabrownin was mediated by the modulation of bile salt hydrolase (BSH)-enriched gut microbiota and bile acid metabolism. In this study, we demonstrated that theabrownin ameliorated high-fat-diet (HFD)-induced obesity by modifying gut microbiota, especially those with 7α-dehydroxylation on the species level, and these changed microbes were positively correlated with secondary bile acid (BA) metabolism. Thus, altered intestinal BAs resulted in shifting bile acid biosynthesis from the classic to the alternative pathway. This shift changed the BA pool by increasing non-12α-hydroxylated-BAs (non-12OH-BAs) and decreasing 12α-hydroxylated BAs (12OH-BAs), which improved energy metabolism in white and brown adipose tissue. This study showed that theabrownin was a potential therapeutic modality for obesity and other metabolic disorders via gut microbiota-driven bile acid alternative synthesis.
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http://dx.doi.org/10.3390/metabo10110475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700314PMC
November 2020

Smart Titanium Coating Composed of Antibiotic Conjugated Peptides as an Infection-Responsive Antibacterial Agent.

Macromol Biosci 2021 01 13;21(1):e2000194. Epub 2020 Oct 13.

Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, P. R. China.

Antibacterial coating is rapidly emerging as a pivotal strategy for mitigating spread of bacterial pathogens. However, many challenges still need to be overcome in order to develop a smart coating that can achieve on-demand antibacterial effects. In this study, a Staphylococcus aureus (S. aureus) sensitive peptide sequence is designed, and an antibiotic is then conjugated with this tailor-made peptide. The antibiotic-peptide conjugate is then linked to the surface of a titanium implant, where the peptide can be recognized and cleaved by an enzyme secreted by S. aureus. This allows for the release of antibiotics in the presence of S. aureus, thus achieving delivery of an antibacterial specifically when an infection occurs.
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http://dx.doi.org/10.1002/mabi.202000194DOI Listing
January 2021

Effects of taraxasterol against ethanol and high-fat diet-induced liver injury by regulating TLR4/MyD88/NF-κB and Nrf2/HO-1 signaling pathways.

Life Sci 2020 Dec 6;262:118546. Epub 2020 Oct 6.

College of Pharmacy, Guilin Medical University, Guilin 541004, Guangxi, China. Electronic address:

Studies have reported that taraxasterol (TAR) is effective in the treatment of immune liver injury and alcoholic liver injury. The mechanism of action is mainly related to the inhibition of inflammation. To determine the key molecular mechanisms for the effect of TAR on alleviating ethanol and high-fat diet-induced liver injury, pathological morphology, biochemistry, oxidative stress, inflammatory response and lipid metabolism were examined. Our results showed that TAR could inhibit ethanol-induced hepatocyte death or lipid accumulation, and suppress oxidative stress, inflammatory response and lipid metabolism disorders. More specifically, ethanol-induced TLR-4 and MyD88 inflammatory response were down-regulated, when treated with TAR. Production of CYP2E1, Nrf2 and HO-1, which produced in response to increased oxidative stress, were regulated in TAR treated, ethanol-induced hepatocytes. In summary, TAR could inhibit the inflammatory response and oxidative stress, which was related to the regulation of TAR on TLR-4/MyD88/NF-κB and Nrf2/HO-1 pathways.
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http://dx.doi.org/10.1016/j.lfs.2020.118546DOI Listing
December 2020

Rapid determination of rosmarinic acid and its two bioactive metabolites in the plasma of rats by LC-MS/MS and application to a pharmacokinetics study.

Biomed Chromatogr 2021 Feb 9;35(2):e4984. Epub 2020 Nov 9.

State Key Laboratory of Component-based Chinese Medicine and Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Rosmarinic acid (RA), an ester compound of caffeic acid (CA) and 3,4-dihydroxyphenyllacic acid, is widely distributed in the herbs of the Lamiaceae family and has shown a wide spectrum of pharmacological properties. CA and FA (ferulic acid) are two bioactive metabolites in vivo after oral administration of RA; however, a rapid and robust analytical approach that can enable the quantitative assay of RA and two bioactive metabolites is still lacking. A liquid chromatography/tandem mass spectrometry method was established that was capable of the quantitative determination of RA, CA and FA by negative-mode multiple reaction monitoring within 7 min using a Zorbax SB-C column and an isocratic elution. This assay method was validated as linear over the investigated ranges with correlation coefficients (r) > 0.9950. The intra- and inter-day precision was <10.65%, and the accuracies (relative error, %) <-6.41%. The validated approach was applied to a pharmacokinetics study of RA and its two metabolites in rats after oral and intravenous administration. RA was rapidly metabolized in both administration modes, whilst the metabolites CA and FA were only detectable by oral administration. The absolute availability of RA was calculated to be 4.13%.
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http://dx.doi.org/10.1002/bmc.4984DOI Listing
February 2021

The effects of Gentiana dahurica Fisch on alcoholic liver disease revealed by RNA sequencing.

J Ethnopharmacol 2020 Sep 29:113422. Epub 2020 Sep 29.

College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, Gansu, 730000, PR China. Electronic address:

Ethnopharmacological Relevance: The root of Gentiana dahurica Fisch (called Qin-Jiao in China), a traditional Chinese medicine, is used in China to treat alcoholic liver disease (ALD), but there has been no scientific report on the treatment of ALD.

Aim Of The Study: To investigate the therapeutic effects of Gentiana dahurica Fisch ethanol extract (GDEE) on ALD and to reveal its possible mechanism of action using RNA sequencing.

Materials And Methods: The model of ALD was established by continuous gavage with alcohol in mice, and GDEE was used to treat ALD. Pathological observation (HE staining, oil red O staining) and biochemical indicators were performed to evaluate liver tissue lesions and efficacy of GDEE. RNA sequencing analysis of liver tissues was carried out to elucidate the pathogenesis of ALD and the mechanism of hepatoprotective effect by GDEE. The RNA sequencing results were verified by detecting mRNA and protein expressions of acetyl coenzyme A carboxylase α (Acacα), fatty acid synthase (Fasn) and carnitine palmitoyltransferase 1A (Cpt1a) by quantitative real-time polymerase chain reaction (PCR) and Western blot.

Results: Measurements of biochemical parameters showed that GDEE could inhibit the increased transaminase activities in the serum and lipid levels in the liver caused by alcohol. It was observed that GDEE could alleviate fatty degeneration, edema and cell necrosis caused by alcohol in the liver tissue. RNA sequencing analysis of liver tissues found that 719 genes and 1137 genes were significantly changed by alcohol and GDEE, respectively. GDEE reversed most of the changes in triglycerides synthesis-related genes up-regulated by alcohol. GDEE up-regulated most of the genes involved in the fatty acid degradation in ALD mice, while alcohol had little effect on them. In addition, GDEE suppressed most of the genes involved in cholesterol synthesis that were up-regulated by alcohol. GDEE up-regulated genes related to bile acid synthesis in ALD mice, and down-regulated genes related to bile acid reabsorption, while alcohol had no significant effect on genes related to bile acid metabolism. In the validation experiments, the Acacα, Fasn and Cpt1a expressions quantified by real-time PCR and Western blot were consistent with the RNA sequencing results.

Conclusions: GDEE can alleviate liver damage and steatosis in ALD mice, and its mechanism of action may be related to the process of regulating triglycerides and cholesterol.
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http://dx.doi.org/10.1016/j.jep.2020.113422DOI Listing
September 2020

A novel noble-metal-free MoC-InS heterojunction photocatalyst with efficient charge separation for enhanced photocatalytic H evolution under visible light.

J Colloid Interface Sci 2021 Jan 28;582(Pt B):488-495. Epub 2020 Aug 28.

Beijing Key Laboratory for Science and Application of Functional Molecular and Crystalline Materials, University of Science and Technology Beijing, Beijing 100083, China.

Currently, designing novel noble-metal-free photocatalysts with efficient carriers migration and catalytically active sites have been a researching hotspot in photocatalytic hydrogen evolution. In this paper, a novel noble-metal-free MoC-InS heterojunction was synthesized by a simple hydrothermal method. Morphology characterization revealed InS was attached to MoC. Electrochemical results showed MoC improved the interface conductivity, and promoted the transportation of photogenerated carriers. Under visible light, the optimal MoC-InS composite achieved a H generation rate of 535.58 μmol h g, which was 175.6 and 25.8 times higher than pristine InS (3.05 μmol h g) and InS-1% Pt (20.73 μmol h g). In addition, a reasonable mechanism of the elevated photocatalytic activity was also discussed. This study demonstrates commercial MoC has an important effect of separating carriers and replacing Pt as co-catalyst in heterojunctions. This research also provides a method to design and synthesize new noble-metal-free photocatalysts for excellent hydrogen production activity.
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http://dx.doi.org/10.1016/j.jcis.2020.08.083DOI Listing
January 2021

Maintenance of mid-latitude oceanic fronts by mesoscale eddies.

Sci Adv 2020 Jul 31;6(31):eaba7880. Epub 2020 Jul 31.

Key Laboratory of Physical Oceanography and Frontiers Science Center for Deep Ocean Multispheres and Earth System, Ocean University of China, Qingdao, China.

Oceanic fronts associated with strong western boundary current extensions vent a vast amount of heat into the atmosphere, anchoring mid-latitude storm tracks and facilitating ocean carbon sequestration. However, it remains unclear how the surface heat reservoir is replenished by ocean processes to sustain the atmospheric heat uptake. Using high-resolution climate simulations, we find that the vertical heat transport by ocean mesoscale eddies acts as an important heat supplier to the surface ocean in frontal regions. This vertical eddy heat transport is not accounted for by the prevailing inviscid and adiabatic ocean dynamical theories such as baroclinic instability and frontogenesis but is tightly related to the atmospheric forcing. Strong surface cooling associated with intense winds in winter promotes turbulent mixing in the mixed layer, destructing the vertical shear of mesoscale eddies. The restoring of vertical shear induces an ageostrophic secondary circulation transporting heat from the subsurface to surface ocean.
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http://dx.doi.org/10.1126/sciadv.aba7880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399485PMC
July 2020

Hydroxyapatite based biocomposite scaffold: A highly biocompatible material for bone regeneration.

Saudi J Biol Sci 2020 Aug 23;27(8):2143-2148. Epub 2020 May 23.

Department of Orthopaedics, Shanghai Pudong New Area Gongli Hospital, Shanghai city 200120, China.

The conventional approaches for treating bone defects such as autografts donor tissue shortages and allografts transmission of diseases pose many shortcomings. The objective of this study was to design a nano strontium/magnesium doped hydroxyapatite (Sr/Mg-HA) with chitosan (CTS) and multi-walled carbon nanotubes (MWCNT) (Sr/Mg-HA/MWCNT/CTS) biocomposite was created to support the growth of osteoblasts using a solvent evaporation method. To help the growth of osteoblasts, a solvent evaporation technique was used to design a nano strontium/magnesium doped hydroxyapatite with chitosan and multi-walled carbon nanotubes biocomposite. We studied the biocompatibility and efficiency in vitro of biocomposite following physicochemical analyzes. Tests of biocompatibility, cell proliferation, mineralization, and osteogenic differentiation have shown that in-vitro safety and effectiveness of biocomposite are good. The performance of biocomposite was more efficient in in-vitro as well as in vivo experiments than in Sr/Mg-HA nanoparticles. Briefly, the Sr/Mg-HA/MWCNT/CTS biocomposite is an ideal candidate for effective bone repair in clinics with excellent mechanical properties with durable multi-biofunctional antibacterial properties and osteoinductivity.
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http://dx.doi.org/10.1016/j.sjbs.2020.05.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384365PMC
August 2020

Functional Integration of Two CYP450 Genes Involved in Biosynthesis of Tanshinones for Improved Diterpenoid Production by Synthetic Biology.

ACS Synth Biol 2020 07 3;9(7):1763-1770. Epub 2020 Jul 3.

State Key Laboratory Breeding Base of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.

Cytochrome P450s (CYPs) are important enzymes in the secondary metabolism of plants and have been recognized as key players in bioengineering and synthetic biology. Previously reported CYP76AH1 and CYP76AH3, having greater than 80% sequence homology, played a continuous catalytic role in the biosynthesis of tanshinones in . Homology modeling indicates that four sites might be responsible for differences in catalytic activity between the two enzymes. A series of modeling-based mutational variants of CYP76AH1 were designed to integrate the functions of the two CYPs. The mutant CYP76AH1, which integrated the functions of CYP76AH1 and CYP76AH3, was found to efficiently catalyze C11 and C12 hydroxylation and C7 oxidation of miltiradiene substrates. Integration and utilization of CYP76AH1 by synthetic biology methods allowed the robust production of 11-hydroxy ferruginol, sugiol, and 11-hydroxy sugiol in yeast. The functionally integrated CYP gene after active site modifications improves catalytic efficiency by reducing the transfer of intermediate metabolites between component proteins. This provides a synthetic biology reference for improving the catalytic efficiencies of systems that produce plant natural products in microorganisms.
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http://dx.doi.org/10.1021/acssynbio.0c00136DOI Listing
July 2020

Research on the reconfigurable bottle beam based on adjusting the spot shape of the incident beam.

Appl Opt 2020 Jun;59(16):4821-4825

An optical system was designed that can generate a bottle beam with a reconfigurable function. The incident beam is produced by transmitting a circular Gaussian beam through the oblique circular aperture, effectively forming the elliptic beam spot. Due to the asymmetry of the elliptically limited Gaussian beam, the bottle beam with locally vanishing light intensity is generated after the optical system. The results show that the bottle beam can be opened and closed freely by the oblique circular aperture, which is of great significance to particle capture.
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http://dx.doi.org/10.1364/AO.390455DOI Listing
June 2020

Antidepressant effects of 3-(3,4-methylenedioxy-5-trifluoromethyl phenyl)-2E-propenoic acid isobutyl amide involve TSPO-mediated mitophagy signalling pathway.

Basic Clin Pharmacol Toxicol 2020 Nov 23;127(5):380-388. Epub 2020 Jul 23.

Medical College, Tibet University, Lhasa, China.

Piper laetispicum C. DC is one of the Chinese herbal medicines used for alleviating depressive disorders. G11-5 [3-(3, 4-methylenedioxy-5-trifluoromethyl phenyl)-2E-propenoic acid isobutyl amide] is synthesized based on the chemical structure of an active integrant of Piper laetispicum C. DC. The present study assessed the antidepressant effect of G11-5 and investigated the underlying mechanism with learned helplessness (LH) and social defeat stress (SDS) mice model of depression. In the LH model, mice were exposed to 60 inescapable electric shocks once a day for three consecutive days followed by 2-week drug administration and helpless behaviour assessment. In the SDS model, mice were subjected to repeated social defeat by an aggressive CD-1 mouse once a day for consecutive 10 days. Following oral administration for 2 weeks, the mice were subjected to a series of behavioural tests including social interaction test. G11-5 significantly decreased the number of escape failures induced by LH paradigm, meanwhile increased the social interaction ratio and shortened the immobility time in forced swimming test for the SDS-exposed mice, suggesting remarkable antidepressant effect. Moreover, G11-5 ameliorated the changes in mitophagy-related proteins induced by two stress exposures and restored retrograde axonal transport and neurotransmitter release. Our findings suggested that G11-5 exhibited an obvious antidepressant through TSPO-mediated mitophagy pathway.
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http://dx.doi.org/10.1111/bcpt.13452DOI Listing
November 2020

Fenestrated/Branched Endovascular Repair for Postdissection Thoracoabdominal Aneurysms: A Systematic Review with Pooled Data Analysis.

Vasc Endovascular Surg 2020 Aug 21;54(6):510-518. Epub 2020 May 21.

Department of Vascular Surgery, Chinese PLA General Hospital, Haidian District, Beijing, People's Republic of China.

Purpose: Patients who have survived an acute aortic dissection remain at risk for postdissection thoracoabdominal aortic aneurysms (PD-TAAAs). Fenestrated/branched endovascular repair for PD-TAAA is increasingly used in some high-volume centers, but outcomes are still limited because of the additional challenges compared to atherosclerotic thoracoabdominal aneurysms. This study was performed to evaluate the literature on fenestrated/branched endovascular repair for PD-TAAAs.

Methods: PubMed, Embase, and the Cochrane Database were searched for relevant studies published until September 2019. Outcome data were extracted to evaluate the technical success, 30-day mortality, later survival, major complications, endoleaks, target vessel patency, and reintervention. Studies were analyzed in a pooled proportion meta-analysis.

Results: In total, 143 patients from 4 studies were identified for the pooled data analysis. The pooled technical success rate was 98% (95% CI: 86%-100%). After the treatment, the overall estimated 30-day mortality rate was 3% (95% CI: 1%-8%), early spinal cord ischemia rate was 10% (95% CI: 4%-21%), early renal injury rate was 5% (95% CI: 1%-19%), endoleak rate was 33% (95% CI: 22%-47%), reintervention rate at a median follow-up of 22.5 months was 34% (95% CI: 27%-42%), and all-cause mortality rate was 12% (95% CI: 6%-24%).

Conclusions: The use of fenestrated/branched stent grafts for the treatment of PD-TAAA appears generally feasible based on the limited literature, but endoleaks and reinterventions are frequent.
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http://dx.doi.org/10.1177/1538574420927131DOI Listing
August 2020

[Progress in Clinical Research of Amide Proton Transfer Imaging].

Zhongguo Yi Liao Qi Xie Za Zhi 2020 Feb;44(2):185-188

Department of Radiology, Children's Hospital Affiliated to Zhejiang University School of Medicine, Hangzhou, 310052.

As a new type of magnetic resonance imaging method, amide proton transfer (APT) imaging can detect the chemical exchange characteristics of free proprotein, peptide amide proton and water proton by water signal changes, reflecting the changes of protein and pH in tissues. In recent years, clinical research on brain tumors, multiple sclerosis, hepatic encephalopathy and cervical cancer have been carried out. It is a radiation-free and non-invasive new magnetic resonance molecular imaging technology. This study briefly reviews the principle of APT technology and its clinical application, and prospects its application prospects in children's abdominal tumors.
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http://dx.doi.org/10.3969/j.issn.1671-7104.2020.02.018DOI Listing
February 2020

The Effects of B1344, a Novel Fibroblast Growth Factor 21 Analog, on Nonalcoholic Steatohepatitis in Nonhuman Primates.

Diabetes 2020 08 30;69(8):1611-1623. Epub 2020 Apr 30.

CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China

Nonalcoholic steatohepatitis has emerged as a major cause of liver diseases with no effective therapies. Here, we evaluate the efficacies and pharmacokinetics of B1344, a long-acting polyethylene glycolylated (PEGylated) fibroblast growth factor 21 analog, in a nongenetically modified nonhuman primate species that underwent liver biopsy and demonstrate the potential for efficacies in humans. B1344 is sufficient to selectively activate signaling from the βKlotho/FGFR1c receptor complex. In cynomolgus monkeys with nonalcoholic fatty liver disease (NAFLD), administration of B1344 via subcutaneous injection for 11 weeks caused a profound reduction of hepatic steatosis, inflammation, and fibrosis, along with amelioration of liver injury and hepatocyte death, as evidenced by liver biopsy specimen and biochemical analysis. Moreover, improvement of metabolic parameters was observed in the monkeys, including reduction of body weight and improvement of lipid profiles and glycemic control. To determine the role of B1344 in the progression of murine NAFLD independent of obesity, B1344 was administered to mice fed a methionine- and choline-deficient diet. Consistently, B1344 administration prevented the mice from lipotoxicity damage and nonalcoholic steatohepatitis in a dose-dependent manner. These results provide preclinical validation for an innovative therapeutic approach to NAFLD and support further clinical testing of B1344 for treating nonalcoholic steatohepatitis and other metabolic diseases in humans.
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http://dx.doi.org/10.2337/db20-0209DOI Listing
August 2020

Transnitrosylation Mediated by the Non-canonical Catalase ROG1 Regulates Nitric Oxide Signaling in Plants.

Dev Cell 2020 05 23;53(4):444-457.e5. Epub 2020 Apr 23.

State Key Laboratory of Plant Genomics, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences, Beijing 100101, China. Electronic address:

The redox-based protein S-nitrosylation is a conserved mechanism modulating nitric oxide (NO) signaling and has been considered mainly as a non-enzymatic reaction. S-nitrosylation is regulated by the intracellular NO level that is tightly controlled by S-nitrosoglutathione reductase (GSNOR). However, the molecular mechanisms regulating S-nitrosylation selectivity remain elusive. Here, we characterize an Arabidopsis "repressor of" gsnor1 (rog1) mutation that specifically suppresses the gsnor1 mutant phenotype. ROG1, identical to the non-canonical catalase, CAT3, is a transnitrosylase that specifically modifies GSNOR1 at Cys-10. The transnitrosylase activity of ROG1 is regulated by a unique and highly conserved Cys-343 residue. A ROG1 mutant displays increased catalase but decreased transnitrosylase activities. Consistent with these results, the rog1 mutation compromises responses to NO under both normal and stress conditions. We propose that ROG1 functions as a transnitrosylase to regulate the NO-based redox signaling in plants.
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http://dx.doi.org/10.1016/j.devcel.2020.03.020DOI Listing
May 2020

Preclinical evaluation of an endovascular sealing device for distal re-entry tears in type B aortic dissection in a porcine model.

Int J Cardiol 2020 08 17;313:108-113. Epub 2020 Apr 17.

Department of Vascular and Endovascular Surgery, Chinese PLA General Hospital, Beijing, China.

Objectives: The objective of present study was to evaluate the feasibility and safety of a novel endovascular sealing device for distal re-entry tears in type B aortic dissection in a porcine model.

Background: Distal re-entry tears are a well-recognized risk factor for unfavorable aortic remodeling after thoracic endovascular aortic repair. However, there is currently no device for sealing a distal re-entry tear.

Methods: We implanted the ENDOPATCH device (Weiqiang Medical, Hangzhou, China) in 15 pigs (40-50 kg) under angiographic guidance. The device can be retrieved and repositioned with an 8-10 French sheath. All pigs were assessed using angiography before sacrifice 1- (n = 1), 3- (n = 1), and 6 months (n = 13) after implantation, which was followed by gross specimen evaluation and histological examination of harvested tissues.

Results: The ENDOPATCH device was successfully implanted in all 15 pigs. The mean disk diameter of the implant was 10.3 ± 1.7 mm, and the chosen device was 4.4 ± 0.9 mm larger than the measured maximum diameter of the fistula. No device migration or leakage was observed angiographically, before sacrifice. An organized thrombus on the disk surface was found in the inferior vena cava of one pig. Complete sealing of the fistula was confirmed by gross and microscopic examinations in all pigs.

Conclusions: Our results indicated that the ENDOPATCH device is feasible and safe in a porcine model. Human studies are needed to evaluate the safety and efficacy of the ENDOPATCH.
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http://dx.doi.org/10.1016/j.ijcard.2020.04.045DOI Listing
August 2020

UFLC-MS/MS Determination and Population Pharmacokinetic Study of Tanshinol, Ginsenoside Rb1 and Rg1 in Rat Plasma After Oral Administration of Compound Danshen Dripping Pills.

Eur J Drug Metab Pharmacokinet 2020 Aug;45(4):523-533

Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, 210009, China.

Background And Objectives: As a traditional Chinese Materia Medica (CMM), the Compound Danshen Dripping Pill (CDDP) is widely used for the treatments of cardiovascular diseases. In view of its undefined applicable population and dosage, a population pharmacokinetic (PPK) study is required. The objective of this study was to explore the feasibility of multi-component CMM PPK in rat plasma after oral administration of CDDP based on sparse sampling.

Methods: In this research, a simple, rapid and highly sensitive UFLC-MS/MS method for the simultaneous determination of tanshinol (TSL), ginsenoside Rb1 (GRb1) and ginsenoside Rg1 (GRg1) has been successfully developed in rat plasma. Moreover, the validated method has been applied to a PPK study of CDDP based on sparse data. We established the PPK models for these three main active constituents using a nonlinear mixed-effects model, taking into account of factors such as gender, age in weeks and weight.

Results: The PPK models of TSL and GRb1 were best described by a one-compartment model with linear elimination and first-order absorption. The model of GRg1 was best described by a two-compartment model with first-order absorption. Bootstrap validation and a visual predictive check confirmed the predictive ability, the model stability and the precision of the parameter estimates from these models.

Conclusion: As a preliminary exploration toward the clinical population pharmacokinetic research, this study provides a reference for the population pharmacokinetic study of traditional CMM.
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http://dx.doi.org/10.1007/s13318-020-00618-4DOI Listing
August 2020

Altered aortic arch geometry in patients with type B aortic dissection.

Eur J Cardiothorac Surg 2020 10;58(4):714-721

Department of Vascular and Endovascular Surgery, Chinese PLA General Hospital, Beijing, China.

Objectives: This study aims to evaluate differences in proximal aorta geometry and identify specific anatomical predictors of type B aortic dissection (TBAD).

Methods: We evaluated computed tomographic angiograms of controls (n = 185) and patients with acute TBAD (n = 173). Using propensity score matching, we created 2 groups of 127 patients. 3mensio Vascular software was used to analyse the computed tomographic angiograms and measure the diameter, length, tortuosity index and angulation of the proximal aorta (divided into ascending aorta and aortic arch). Tortuosity index was calculated by dividing the centre lumen line length of the aortic segment by its shortest length. Angulation was measured by the centre lumen line 'tangent line angle'. Two independent multivariable models identified significant anatomical associations regarding the tortuosity and angulation geometry.

Results: Aortic diameter and ascending aorta and aortic arch lengths in TBAD increased significantly. The aortic arch tortuosity was significantly higher in the TBAD group (P < 0.001), with no difference regarding the ascending aorta (P = 0.11). Ascending aorta and aortic arch angulation were significantly higher in the TBAD group (P = 0.01, P < 0.001, respectively). Multivariable analyses showed that increased aortic arch tortuosity and angulation were significant predictors of the development of TBAD [odds ratio (OR) 1.91, 95% confidence interval (CI) 1.40-2.59; P < 0.001 and OR 1.08, 95% CI 1.04-1.12; P < 0.001], respectively.

Conclusions: In addition to proximal aorta dilation and elongation, we identified increased aortic arch tortuosity and angulation as possible specific predictors of TBAD.
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http://dx.doi.org/10.1093/ejcts/ezaa102DOI Listing
October 2020

Application of a Reversed Off-the-Shelf Iliac Branched Device Stent in Revascularization of the Renal Artery Originating from the False Lumen.

Ann Vasc Surg 2020 Aug 28;67:569.e1-569.e7. Epub 2020 Mar 28.

Department of Vascular Surgery, Chinese PLA General Hospital, Beijing, People's Republic of China. Electronic address:

Fenestrated/branched endovascular aneurysm repair is a feasible and effective treatment option for patients with postdissection thoracoabdominal/abdominal aneurysm. However, this technique is cumbersome when the target vessel originates from the false lumen. We herein report our primary experiences in utilizing a reversed off-the-shelf iliac branched device (IBD) stent to reconstruct the renal artery originating from the false lumen. This technique was performed in 3 patients (all men; 49, 46, and 45 years old) in our center. After deployment of the main aortic endograft, the distal re-entry in the common iliac artery was dilated by a balloon. The off-the-shelf IBD was then reversely deployed to allow for deployment of the bridging stent graft. Finally, the IBD and the bridging stents were assembled and the IBD was connected to the main graft. No migration of the IBDs occurred, and all target vessels remained patent during follow-up. Utilization of a reversed off-the-shelf IBD for the renal artery originating from the false lumen is a feasible option, especially for patients with specific anatomical characteristics of postdissection aortic aneurysms.
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http://dx.doi.org/10.1016/j.avsg.2020.03.026DOI Listing
August 2020

2-Methyltetrol sulfate ester-initiated nucleation mechanism enhanced by common nucleation precursors: A theory study.

Sci Total Environ 2020 Jun 17;723:137987. Epub 2020 Mar 17.

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

Aerosol samples from all over the word contained 2-methyltetrol sulfate ester (MTS). We investigated the role of MTS in new particle formation (NPF) with aerosol nucleation precursors, including sulfuric acid (SA), water (W), ammonia (N), methylamine (MA), dimethylamine (DMA), and trimethylamine (TMA). The analysis was performed using quantum chemical approach, kinetic calculation and molecular dynamics (MD) simulations. The results proved that the molecular interactions in the clusters were mainly H-bonds and electrostatic interaction. The negative Gibbs free energy changes for all the studied MTS-containing clusters indicated that the formation of these clusters was thermodynamically favorable. The stability of the clusters was evaluated according to the total evaporation rate. Here, (MTS)(SA) and (MTS)(W) were the most and least stable cluster, respectively. MD simulations were used for time and spatial analysis of the role of the MTS-SA system. The results indicated that MTS can self-aggregate or absorb SA molecules into clusters, larger than the size of the critical cluster (approximately 1 nm), suggesting that MTS can initiate NPF by itself or together with SA.
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http://dx.doi.org/10.1016/j.scitotenv.2020.137987DOI Listing
June 2020

Efficacy and safety of thromboprophylaxis in cancer patients: a systematic review and meta-analysis.

Ther Adv Med Oncol 2020 18;12:1758835920907540. Epub 2020 Mar 18.

Department of Critical Care Medicine, Harbin Medical University Cancer Hospital, No. 150 Haping Rd., Nangang District, Harbin, 150081, China.

Background: Thrombosis is a common complication in patients with cancer. Whether thromboprophylaxis could benefit patients with cancer is unclear. The aim of this systematic review was to determine the efficacy and safety of thromboprophylaxis in patients with cancer undergoing surgery or chemotherapy.

Methods: We searched the Cochrane Library, EMBASE, MEDLINE, EBSCOhost, and Web of Science for studies published before May 2018 to investigate whether thromboprophylaxis measures were more effective than a placebo in patients with cancer.

Results: In total, 33 trials with 11,942 patients with cancer were identified. In patients with cancer undergoing surgery, the administration of thromboprophylaxis was associated with decreasing trends in venous thromboembolism (VTE) [relative risk (RR) 0.51, 95% confidence interval (CI) 0.32-0.81] and DVT (RR 0.53, 95% CI 0.33-0.87). In patients with cancer undergoing chemotherapy, the administration of thromboprophylaxis reduced the incidences of VTE, DVT, and pulmonary embolism compared with no thromboprophylaxis (RR 0.54, 95% CI 0.40-0.73; RR 0.47, 95% CI 0.31-0.73; RR 0.51, 95% CI 0.32-0.81, respectively). The pooled results regarding major bleeding showed no significant difference between prophylaxis and no prophylaxis in either the surgical or the chemotherapy groups (RR 2.35, 95% CI 0.74-7.52,  = 0.1482, I = 0%; RR 1.30, 95% CI 0.93-1.83,  = 0.1274, I = 0%, respectively).

Conclusion: Thromboprophylaxis did not increase major bleeding events or the incidence of thrombocytopenia. All-cause mortality was not significantly different between those who received thromboprophylaxis and those who did not. This meta-analysis provides evidence that thromboprophylaxis can reduce the number of VTE and DVT events, with no apparent increase in the incidence of major bleeding in patients with cancer.
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http://dx.doi.org/10.1177/1758835920907540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081475PMC
March 2020

Determination of the amine-catalyzed SO hydrolysis mechanism in the gas phase and at the air-water interface.

Chemosphere 2020 Aug 25;252:126292. Epub 2020 Feb 25.

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

New particle formation (NPF) involving amines in the atmosphere is considered an aggregation process, during which stable molecular clusters are formed from amines and sulfuric acid via hydrogen bond interaction. In this work, ab initio dynamics simulations of ammonium bisulfate formation from a series of amines, SO, and HO molecules were carried out in the gas phase and at the air-water interface. The results show that reactions between amines and hydrated SO molecules in the gas phase are barrierless or nearly barrierless processes. The reaction rate is related to the basicity of gas-phase amines-the stronger the basicity, the faster the reaction. Furthermore, SO hydrolysis catalyzed by amines occurs simultaneously with HSO-amine cluster formation. At the air-water interface, reactions between amines and SO involve multiple water molecules. The reaction center's ring structure (amine-SO-nHO) promotes the transfer of protons in the water molecules. The formed ammonium cation (-RNH) and the bisulfate anion (HSO) are present and stable by means of hydrogen bond interaction. The cluster formation mechanism provides new insights into NPF involving amines, which may play an important role in the formation of aerosols in some heavily polluted areas - e.g., those with a high amine concentration.
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http://dx.doi.org/10.1016/j.chemosphere.2020.126292DOI Listing
August 2020