Publications by authors named "Xinyue Liu"

180 Publications

A Semiautomated Paramagnetic Bead-Based Platform for Isobaric Tag Sample Preparation.

J Am Soc Mass Spectrom 2021 May 5. Epub 2021 May 5.

Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, United States.

The development of streamlined and high-throughput sample processing workflows is important for capitalizing on emerging advances and innovations in mass spectrometry-based applications. While the adaptation of new technologies and improved methodologies is fast paced, automation of upstream sample processing often lags. Here we have developed and implemented a semiautomated paramagnetic bead-based platform for isobaric tag sample preparation. We benchmarked the robot-assisted platform by comparing the protein abundance profiles of six common parental laboratory yeast strains in triplicate TMTpro16-plex experiments against an identical set of experiments in which the samples were manually processed. Both sets of experiments quantified similar numbers of proteins and peptides with good reproducibility. Using these data, we constructed an interactive website to explore the proteome profiles of six yeast strains. We also provide the community with open-source templates for automating routine proteomics workflows on an opentrons OT-2 liquid handler. The robot-assisted platform offers a versatile and affordable option for reproducible sample processing for a wide range of protein profiling applications.
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http://dx.doi.org/10.1021/jasms.1c00077DOI Listing
May 2021

Transcriptomics and metabolomics reveal the adaption of Akkermansia muciniphila to high mucin by regulating energy homeostasis.

Sci Rep 2021 Apr 27;11(1):9073. Epub 2021 Apr 27.

Key Laboratory of Meat Processing and Quality Control, Ministry of Education, Key Laboratory of Meat Processing, Ministry of Agriculture and Rural Affairs, Jiangsu Collaborative Innovation Centre of Meat Production and Processing, Quality and Safety Control, Meat Production, College of Food Science and Technology, Nanjing Agricultural University, Weigang 1#, Nanjing, 210095, People's Republic of China.

In gut, Akkermansia muciniphila (A. muciniphila) probably exerts its probiotic activities by the positive modulation of mucus thickness and gut barrier integrity. However, the potential mechanisms between A. muciniphila and mucin balance have not been fully elucidated. In this study, we cultured the bacterium in a BHI medium containing 0% to 0.5% mucin, and transcriptome and gas chromatography mass spectrometry (GC-MS) analyses were performed. We found that 0.5% (m/v) mucin in a BHI medium induced 1191 microbial genes to be differentially expressed, and 49 metabolites to be changed. The metabolites of sorbose, mannose, 2,7-anhydro-β-sedoheptulose, fructose, phenylalanine, threonine, lysine, ornithine, asparagine, alanine and glutamic acid were decreased by 0.5% mucin, while the metabolites of leucine, valine and N-acetylneuraminic acid were increased. The association analysis between transcriptome and metabolome revealed that A. muciniphila gave strong responses to energy metabolism, amino sugar and nucleotide sugar metabolism, and galactose metabolism pathways to adapt to high mucin in the medium. This finding showed that only when mucin reached a certain concentration in a BHI medium, A. muciniphila could respond to the culture environment significantly at the level of genes and metabolites, and changed its metabolic characteristics by altering the effect on carbohydrates and amino acids.
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http://dx.doi.org/10.1038/s41598-021-88397-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079684PMC
April 2021

The effects of Fushen Granule on the composition and function of the gut microbiota during Peritoneal Dialysis-Related Peritonitis.

Phytomedicine 2021 Mar 28;86:153561. Epub 2021 Mar 28.

Department of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, PR China. Electronic address:

Background: Peritoneal dialysis (PD) is an acknowledged treatment for patients with irreversible kidney failure. The treatment usually causes peritoneal dialysis-related peritonitis (PDRP), a common complication of PD that can lead to inadequate dialysis, gastrointestinal dysfunction, and even death. Recent studies indicated that Fushen Granule (FSG), a Chinese herbal formula, improves the treatment of PD. However, the mechanism of how FSG plays its role in the improvement is still unclear. Gut microbiota has been closely related to the development of various diseases. We carried out a randomized controlled trial to assess whether FSG can modulate the gut microbiota during PDRP treatment.

Methods: Forty-two PDRP patients were recruited into the clinical trial, and they were randomly divided into control(CON), probiotics(PRO) or Fushen granule group(FSG). To check whether FSG improve the PD treatment, we assessed the clinical parameters, including albumin(ALB), hemoglobin(HGB), blood urea nitrogen(BUN) and creatinine(CR). Fecal samples were collected before hospitalization and discharge, and stored at -80°C within 1 hour. And we assessed the microbial population and function by applying the 16S rRNA gene sequencing and functional enrichment analysis.

Results: Compared to control group, ALB is improved in both probiotics and FSG groups, while HGB is increased but BUN and CR is reduced in FSG group. Sequencing of 16S rRNA genes revealed that FSG and PRO affected the composition of the microbial community. FSG significantly increased a abundant represented by Bacteroides, Megamonas and Rothia, which was significantly correlated with the improvements in carbohydrate and amino acid metabolism.

Conclusions: This study demonstrates that FSG ameliorates the nutritional status and improves the quality of life by enriching beneficial bacteria associated with metabolism. These results indicate that FSG as alternative medicine is a promising treatment for patients with PDRP.
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http://dx.doi.org/10.1016/j.phymed.2021.153561DOI Listing
March 2021

Interference of nuclear mitochondrial DNA segments in mitochondrial DNA testing resembles biparental transmission of mitochondrial DNA in humans.

Genet Med 2021 Apr 12. Epub 2021 Apr 12.

GeneDx Inc, Gaithersburg, MD, USA.

Purpose: Reports have questioned the dogma of exclusive maternal transmission of human mitochondrial DNA (mtDNA), including the recent report of an admixture of two mtDNA haplogroups in individuals from three multigeneration families. This was interpreted as being consistent with biparental transmission of mtDNA in an autosomal dominant-like mode. The authenticity and frequency of these findings are debated.

Methods: We retrospectively analyzed individuals with two mtDNA haplogroups from 2017 to 2019 and selected four families for further study.

Results: We identified this phenomenon in 104/27,388 (approximately 1/263) unrelated individuals. Further study revealed (1) a male with two mitochondrial haplogroups transmits only one haplogroup to some of his offspring, consistent with nuclear transmission; (2) the heteroplasmy level of paternally transmitted variants is highest in blood, lower in buccal, and absent in muscle or urine of the same individual, indicating it is inversely correlated with mtDNA content; and (3) paternally transmitted apparent large-scale mtDNA deletions/duplications are not associated with a disease phenotype.

Conclusion: These findings strongly suggest that the observed mitochondrial haplogroup of paternal origin resulted from coamplification of rare, concatenated nuclear mtDNA segments with genuine mtDNA during testing. Evaluation of additional specimen types can help clarify the clinical significance of the observed results.
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http://dx.doi.org/10.1038/s41436-021-01166-1DOI Listing
April 2021

Soft Materials by Design: Unconventional Polymer Networks Give Extreme Properties.

Chem Rev 2021 Apr 12;121(8):4309-4372. Epub 2021 Apr 12.

Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.

Hydrogels are polymer networks infiltrated with water. Many biological hydrogels in animal bodies such as muscles, heart valves, cartilages, and tendons possess extreme mechanical properties including being extremely tough, strong, resilient, adhesive, and fatigue-resistant. These mechanical properties are also critical for hydrogels' diverse applications ranging from drug delivery, tissue engineering, medical implants, wound dressings, and contact lenses to sensors, actuators, electronic devices, optical devices, batteries, water harvesters, and soft robots. Whereas numerous hydrogels have been developed over the last few decades, a set of general principles that can rationally guide the design of hydrogels using different materials and fabrication methods for various applications remain a central need in the field of soft materials. This review is aimed at synergistically reporting: (i) general design principles for hydrogels to achieve extreme mechanical and physical properties, (ii) implementation strategies for the design principles using , and (iii) future directions for the orthogonal design of hydrogels to achieve multiple combined mechanical, physical, chemical, and biological properties. Because these design principles and implementation strategies are based on generic polymer networks, they are also applicable to other soft materials including elastomers and organogels. Overall, the review will not only provide comprehensive and systematic guidelines on the rational design of soft materials, but also provoke interdisciplinary discussions on a fundamental question: why does nature select soft materials with unconventional polymer networks to constitute the major parts of animal bodies?
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http://dx.doi.org/10.1021/acs.chemrev.0c01088DOI Listing
April 2021

Hydrogel-based biocontainment of bacteria for continuous sensing and computation.

Nat Chem Biol 2021 Apr 5. Epub 2021 Apr 5.

Synthetic Biology Group, Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, USA.

Genetically modified microorganisms (GMMs) can enable a wide range of important applications including environmental sensing and responsive engineered living materials. However, containment of GMMs to prevent environmental escape and satisfy regulatory requirements is a bottleneck for real-world use. While current biochemical strategies restrict unwanted growth of GMMs in the environment, there is a need for deployable physical containment technologies to achieve redundant, multi-layered and robust containment. We developed a hydrogel-based encapsulation system that incorporates a biocompatible multilayer tough shell and an alginate-based core. This deployable physical containment strategy (DEPCOS) allows no detectable GMM escape, bacteria to be protected against environmental insults including antibiotics and low pH, controllable lifespan and easy retrieval of genomically recoded bacteria. To highlight the versatility of DEPCOS, we demonstrated that robustly encapsulated cells can execute useful functions, including performing cell-cell communication with other encapsulated bacteria and sensing heavy metals in water samples from the Charles River.
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http://dx.doi.org/10.1038/s41589-021-00779-6DOI Listing
April 2021

The Mechanisms and Functions of GDF-5 in Intervertebral Disc Degeneration.

Orthop Surg 2021 Apr 4. Epub 2021 Apr 4.

Spinal Surgery Department, Hospital (T.C.M) Affiliated to Southwest Medical University, Luzhou, China.

Intervertebral disc degeneration (IDD) is widely recognized as the main cause of low back pain, which leads to disability in aging populations and induces great losses both socially and economically worldwide. Unfortunately, current treatments for IDD are aimed at relieving symptoms instead of preserving disc structure and function. Researchers are forged to find new promising biological therapeutics to stop, and even reverse, IVD degeneration. Recently, the injection of growth factors has been shown to be a promising biological therapy for IDD. A number of growth factors have been investigated to modulate the synthesis of the extracellular matrix (ECM) through a variety of pathogenetic biological mechanisms, including suppressing inflammatory process and down-regulating degrading enzymes. However, growth factors, including Transforming Growth Factor-β (TGF-β), Fibroblast Growth Factor (FGF), and Insulin-like Growth Factor-1 (IGF-1), may induce unwanted blood vessel in-growth, which accelerates the process of IDD. On the contrary, studies have demonstrated that injection of GDF-5 into the intervertebral disc of mice can effectively alleviate the degeneration of the intervertebral disc, which elicits their response via BMPRII and will not induce blood vessel in-growth. This finding suggests that GDF-5 is more suitable for use in IDD treatment compared with the three other growth factors. Substantial evidence has suggested that GDF-5 may maintain the structure and function of the intervertebral disc (IVD). GDF-5 plays an important role in IDD and is a very promising therapeutic agent for IDD. This review is focused on the mechanisms and functions of GDF-5 in IDD.
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http://dx.doi.org/10.1111/os.12942DOI Listing
April 2021

One-step vapor deposition of fluorinated polycationic coating to fabricate antifouling and anti-infective textile against drug-resistant bacteria and viruses.

Chem Eng J 2021 Aug 16;418:129368. Epub 2021 Mar 16.

Ningbo Institute, Frontiers Science Center for Flexible Electronics (FSCFE), Xi'an Institute of Flexible Electronics (IFE) and Xi'an Institute of Biomedical Materials & Engineering (IBME), Northwestern Polytechnical University, 127 West Youyi Road, Xi'an 710072, China.

The ongoing pandemic caused by the novel coronavirus has turned out to be one of the biggest threats to the world, and the increase of drug-resistant bacterial strains also threatens the human health. Hence, there is an urgent need to develop novel anti-infective materials with broad-spectrum anti-pathogenic activity. In the present study, a fluorinated polycationic coating was synthesized on a hydrophilic and negatively charged polyester textile via one-step initiated chemical vapor deposition of poly(dimethyl amino methyl styrene--1H,1H,2H,2H-perfluorodecyl acrylate) (P(DMAMS--PFDA), PDP). The surface characterization results of SEM, FTIR, and EDX demonstrated the successful synthesis of PDP coating. Contact angle analysis revealed that PDP coating endowed the polyester textile with the hydrophobicity against the attachment of different aqueous foulants such as blood, coffee, and milk, as well as the oleophobicity against paraffin oil. Zeta potential analysis demonstrated that the PDP coating enabled a transformation of negative charge to positive charge on the surface of polyester textile. The PDP coating exhibited excellent contact-killing activity against both gram-negative and gram-positive methicillin-resistant , with the killing efficiency of approximate 99.9%. In addition, the antiviral capacity of PDP was determined by a green fluorescence protein (GFP) expression-based method using lentivirus-EGFP as a virus model. The PDP coating inactivated the negatively charged lentivirus-EGFP effectively. Moreover, the coating showed good biocompatibility toward mouse NIH 3T3 fibroblast cells. All the above properties demonstrated that PDP would be a promising anti-pathogenic polymeric coating with wide applications in medicine, hygiene, hospital, etc., to control the bacterial and viral transmission and infection.
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http://dx.doi.org/10.1016/j.cej.2021.129368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962519PMC
August 2021

SeqEnhDL: sequence-based classification of cell type-specific enhancers using deep learning models.

BMC Res Notes 2021 Mar 19;14(1):104. Epub 2021 Mar 19.

Division of Intramural Clinical and Biological Research (DICBR), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, 20892, USA.

Objective: To address the challenge of computational identification of cell type-specific regulatory elements on a genome-wide scale.

Results: We propose SeqEnhDL, a deep learning framework for classifying cell type-specific enhancers based on sequence features. DNA sequences of "strong enhancer" chromatin states in nine cell types from the ENCODE project were retrieved to build and test enhancer classifiers. For any DNA sequence, positional k-mer (k = 5, 7, 9 and 11) fold changes relative to randomly selected non-coding sequences across each nucleotide position were used as features for deep learning models. Three deep learning models were implemented, including multi-layer perceptron (MLP), Convolutional Neural Network (CNN) and Recurrent Neural Network (RNN). All models in SeqEnhDL outperform state-of-the-art enhancer classifiers (including gkm-SVM and DanQ) in distinguishing cell type-specific enhancers from randomly selected non-coding sequences. Moreover, SeqEnhDL can directly discriminate enhancers from different cell types, which has not been achieved by other enhancer classifiers. Our analysis suggests that both enhancers and their tissue-specificity can be accurately identified based on their sequence features. SeqEnhDL is publicly available at https://github.com/wyp1125/SeqEnhDL .
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http://dx.doi.org/10.1186/s13104-021-05518-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980595PMC
March 2021

pH-dependent and dynamic interactions of cystatin C with heparan sulfate.

Commun Biol 2021 Feb 12;4(1):198. Epub 2021 Feb 12.

Department of Oral Biology, The University at Buffalo, Buffalo, NY, USA.

Cystatin C (Cst-3) is a potent inhibitor of cysteine proteases with diverse biological functions. As a secreted protein, the potential interaction between Cst-3 and extracellular matrix components has not been well studied. Here we investigated the interaction between Cst-3 and heparan sulfate (HS), a major component of extracellular matrix. We discovered that Cst-3 is a HS-binding protein only at acidic pH. By NMR and site-directed mutagenesis, we identified two HS binding regions in Cst-3: the highly dynamic N-terminal segment and a flexible region located between residue 70-94. The composition of the HS-binding site by two highly dynamic halves is unique in known HS-binding proteins. We further discovered that HS-binding severely impairs the inhibitory activity of Cst-3 towards papain, suggesting the interaction could actively regulate Cst-3 activity. Using murine bone tissues, we showed that Cst-3 interacts with bone matrix HS at low pH, again highlighting the physiological relevance of our discovery.
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http://dx.doi.org/10.1038/s42003-021-01737-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881039PMC
February 2021

EGCG binds intrinsically disordered N-terminal domain of p53 and disrupts p53-MDM2 interaction.

Nat Commun 2021 02 12;12(1):986. Epub 2021 Feb 12.

Center for Biotechnology and Interdisciplinary Studies, Department of Chemistry and Chemical Biology, Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, NY, USA.

Epigallocatechin gallate (EGCG) from green tea can induce apoptosis in cancerous cells, but the underlying molecular mechanisms remain poorly understood. Using SPR and NMR, here we report a direct, μM interaction between EGCG and the tumor suppressor p53 (K = 1.6 ± 1.4 μM), with the disordered N-terminal domain (NTD) identified as the major binding site (K = 4 ± 2 μM). Large scale atomistic simulations (>100 μs), SAXS and AUC demonstrate that EGCG-NTD interaction is dynamic and EGCG causes the emergence of a subpopulation of compact bound conformations. The EGCG-p53 interaction disrupts p53 interaction with its regulatory E3 ligase MDM2 and inhibits ubiquitination of p53 by MDM2 in an in vitro ubiquitination assay, likely stabilizing p53 for anti-tumor activity. Our work provides insights into the mechanisms for EGCG's anticancer activity and identifies p53 NTD as a target for cancer drug discovery through dynamic interactions with small molecules.
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http://dx.doi.org/10.1038/s41467-021-21258-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881117PMC
February 2021

Exogenous Calcium Alleviates Nocturnal Chilling-Induced Feedback Inhibition of Photosynthesis by Improving Sink Demand in Peanut ().

Front Plant Sci 2020 21;11:607029. Epub 2020 Dec 21.

The UWA Institute of Agriculture, The University of Western Australia, Perth, WA, Australia.

(peanut) is a globally important oilseed crop with high nutritional value. However, upon exposure to overnight chilling stress, it shows poor growth and seedling necrosis in many cultivation areas worldwide. Calcium (Ca) enhances chilling resistance in various plant species. We undertook a pot experiment to investigate the effects of exogenous Ca and a calmodulin (CaM) inhibitor on growth and photosynthetic characteristics of peanut exposed to low night temperature (LNT) stress following warm sunny days. The LNT stress reduced growth, leaf extension, biomass accumulation, gas exchange rates, and photosynthetic electron transport rates. Following LNT stress, we observed larger starch grains and a concomitant increase in nonstructural carbohydrates and hydrogen peroxide (HO) concentrations. The LNT stress further induced photoinhibition and caused structural damage to the chloroplast grana. Exogenous Ca enhanced plant growth following LNT stress, possibly by allowing continued export of carbohydrates from leaves. Foliar Ca likely alleviated the nocturnal chilling-dependent feedback limitation on photosynthesis in the daytime by increasing sink demand. The foliar Ca pretreatment protected the photosystems from photoinhibition by facilitating cyclic electron flow (CEF) and decreasing the proton gradient (pH) across thylakoid membranes during LNT stress. Foliar application of a CaM inhibitor increased the negative impact of LNT stress on photosynthetic processes, confirming that Ca-CaM played an important role in alleviating photosynthetic inhibition due to the overnight chilling-dependent feedback.
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http://dx.doi.org/10.3389/fpls.2020.607029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779555PMC
December 2020

Dimension control of in situ fabricated CsPbClBr nanocrystal films toward efficient blue light-emitting diodes.

Nat Commun 2020 Dec 22;11(1):6428. Epub 2020 Dec 22.

MIIT Key Laboratory for Low-Dimensional Quantum Structure and Devices, School of Materials Science & Engineering, Beijing Institute of Technology, 100081, Beijing, China.

In the field of perovskite light-emitting diodes (PeLEDs), the performance of blue emissive electroluminescence devices lags behind the other counterparts due to the lack of fabrication methodology. Herein, we demonstrate the in situ fabrication of CsPbClBr nanocrystal films by using mixed ligands of 2-phenylethanamine bromide (PEABr) and 3,3-diphenylpropylamine bromide (DPPABr). PEABr dominates the formation of quasi-two-dimensional perovskites with small-n domains, while DPPABr induces the formation of large-n domains. Strong blue emission at 470 nm with a photoluminescence quantum yield up to 60% was obtained by mixing the two ligands due to the formation of a narrower quantum-well width distribution. Based on such films, efficient blue PeLEDs with a maximum external quantum efficiency of 8.8% were achieved at 473 nm. Furthermore, we illustrate that the use of dual-ligand with respective tendency of forming small-n and large-n domains is a versatile strategy to achieve narrow quantum-well width distribution for photoluminescence enhancement.
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http://dx.doi.org/10.1038/s41467-020-20163-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755912PMC
December 2020

Primary Invasive Mucinous Adenocarcinoma of the Lung: Prognostic Value of CT Imaging Features Combined with Clinical Factors.

Korean J Radiol 2021 04 19;22(4):652-662. Epub 2020 Nov 19.

Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Objective: To investigate the association between CT imaging features and survival outcomes in patients with primary invasive mucinous adenocarcinoma (IMA).

Materials And Methods: Preoperative CT image findings were consecutively evaluated in 317 patients with resected IMA from January 2011 to December 2015. The association between CT features and long-term survival were assessed by univariate analysis. The independent prognostic factors were identified by the multivariate Cox regression analyses. The survival comparison of IMA patients was investigated using the Kaplan-Meier method and propensity scores. Furthermore, the prognostic impact of CT features was assessed based on different imaging subtypes, and the results were adjusted using the Bonferroni method.

Results: The median follow-up time was 52.8 months; the 5-year disease-free survival (DFS) and overall survival rates of resected IMAs were 68.5% and 77.6%, respectively. The univariate analyses of all IMA patients demonstrated that 15 CT imaging features, in addition to the clinicopathologic characteristics, significantly correlated with the recurrence or death of IMA patients. The multivariable analysis revealed that five of them, including imaging subtype ( = 0.002), spiculation ( < 0.001), tumor density ( = 0.008), air bronchogram ( < 0.001), emphysema ( < 0.001), and location ( = 0.029) were independent prognostic factors. The subgroup analysis demonstrated that pneumonic-type IMA had a significantly worse prognosis than solitary-type IMA. Moreover, for solitary-type IMAs, the most independent CT imaging biomarkers were air bronchogram and emphysema with an adjusted p value less than 0.05; for pneumonic-type IMA, the tumors with mixed consolidation and ground-glass opacity were associated with a longer DFS (adjusted = 0.012).

Conclusion: CT imaging features characteristic of IMA may provide prognostic information and individual risk assessment in addition to the recognized clinical predictors.
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http://dx.doi.org/10.3348/kjr.2020.0454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005341PMC
April 2021

Plasma Phospholipid -3/-6 Polyunsaturated Fatty Acids and Desaturase Activities in Relation to Moderate-to-Vigorous Physical Activity through Pregnancy: A Longitudinal Study within the NICHD Fetal Growth Studies.

Nutrients 2020 Nov 19;12(11). Epub 2020 Nov 19.

Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.

Maternal plasma phospholipid polyunsaturated fatty acids (PUFAs) play critical roles in maternal health and fetal development. Beyond dietary factors, maternal moderate-to-vigorous physical activity (MVPA) has been linked to multiple health benefits for both the mother and offspring, but studies investigating the influence of maternal MVPA on maternal PUFA profile are scarce. The objective of present study was to examine the time-specific and prospective associations of MVPA with plasma PUFA profile among pregnant women. This study included 321 participants from the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons cohort. Maternal plasma phospholipid PUFAs and MPVA were measured at four visits during pregnancy (10-14, 15-26, 23-31, and 33-39 gestational weeks (GW)). Associations of maternal MVPA with individual plasma PUFAs and desaturase activity were examined using generalized linear models. Maternal MVPA was associated inversely with plasma phospholipid linoleic acid, gamma-linolenic acid, and Δ6-desaturase in late pregnancy (23-31 or 33-39 GW), independent of maternal age, race, education, parity, pre-pregnancy body mass index, and dietary factors. Findings from this longitudinal study indicate that maternal habitual MVPA may play a role on PUFAs metabolism, particular by alerting plasma -6 subclass and desaturase activity in late pregnancy. These associations are novel and merit confirmation in future studies.
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http://dx.doi.org/10.3390/nu12113544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699189PMC
November 2020

A Model for the Solution Structure of Human Fe(II)-Bound Acireductone Dioxygenase and Interactions with the Regulatory Domain of Matrix Metalloproteinase I (MMP-I).

Biochemistry 2020 11 2;59(44):4238-4249. Epub 2020 Nov 2.

Department of Chemistry, Brandeis University, 415 South Street, Waltham, Massachusetts 02454-9110, United States.

The metalloenzyme acireductone dioxygenase (ARD) shows metal-dependent physical and enzymatic activities depending upon the metal bound in the active site. The Fe(II)-bound enzyme catalyzes the penultimate step of the methionine salvage pathway, converting 1,2-dihydroxy-5-(methylthio)pent-1-en-3-one (acireductone) into formate and the ketoacid precursor of methionine, 2-keto-4-thiomethyl-2-oxobutanoate, using O as the oxidant. If Ni(II) is bound, an off-pathway shunt occurs, producing 3-methylthiopropionate, formate, and carbon monoxide from the same acireductone substrate. The solution structure of the Fe(II)-bound human enzyme, HsARD, is described and compared with the structures of Ni-bound forms of the closely related mouse enzyme, MmARD. Potential rationales for the different reactivities of the two isoforms are discussed. The human enzyme has been found to regulate the activity of matrix metalloproteinase I (MMP-I), which is involved in tumor metastasis, by binding the cytoplasmic transmembrane tail peptide of MMP-I. Nuclear magnetic resonance titration of HsARD with the MMP-I tail peptide permits identification of the peptide binding site on HsARD, a cleft anterior to the metal binding site adjacent to a dynamic proline-rich loop.
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http://dx.doi.org/10.1021/acs.biochem.0c00724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768908PMC
November 2020

Nano-sulforaphane attenuates PhIP-induced early abnormal embryonic neuro-development.

Ann Anat 2021 Jan 21;233:151617. Epub 2020 Oct 21.

International Joint Laboratory for Embryonic Development & Prenatal Medicine, Division of Histology and Embryology, Medical College, Jinan University, Guangzhou 510632, China; Key Laboratory for Regenerative Medicine of the Ministry of Education, Jinan University, Guangzhou 510632, China. Electronic address:

Background: 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyrimidine (PhIP), one of the most abundant heterocyclic aromatic amines (HAA) formed by cooking meat at high temperatures, may modify humans and rodents through the metabolic process prior to affecting nervous system development. In humans and rodents may be modified by metabolic processes and then affecting nervous system development.

Methods: In this paper, PhIP was used to prepare a chicken embryo model with abnormal embryonic nervous system defects. Sulforaphane (SFN) is a derivative of a glucosinolate, which is abundant in cruciferous vegetables, and can pass through the placental barrier. Moreover, SFN has antioxidant and anti-apoptotic functions and is considered as a bioactive antioxidant with significant neuroprotective effects. Nano-sulforaphane (Nano-SFN, sulforaphane nanoparticles) was prepared by self-assembly using biocompatible, biodegradable methoxy polyethylene glycol 5000-b-polyglutamic acid 10,000 (mPEG5K-PGA10K) as the substrate, to explore the new application of Nano-SFN and its modified compounds as leading compounds in protecting against the abnormal development of the embryonic nervous system.

Results: The results show that Nano-SFN could protect against PhIP-induced central nervous system (CNS, derived from neural tube) and peripheral nervous system (PNS, derived from neural crest cells, NCCs) defects and neural tube defects (NTDs), and increase the embryo survival rate.

Conclusions: This study indicates that Nano-SFN can effectively alleviate the developmental defects of embryonic nervous system induced by PhIP in the microenvironment and has a protective effect on embryonic development. It not only helps with expanding the application of SFN and improving its medicinal value, but also provides a possibility of SFN being developed as a novel drug for neuroprotection.
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http://dx.doi.org/10.1016/j.aanat.2020.151617DOI Listing
January 2021

Differences in maternal gene expression in Cesarean section delivery compared with vaginal delivery.

Sci Rep 2020 10 20;10(1):17797. Epub 2020 Oct 20.

Inova Children's Hospital, Falls Church, VA, USA.

Cesarean section (CS) is recognized as being a shared environmental risk factor associated with chronic immune disease. A study of maternal gene expression changes between different delivery modes can add to our understanding of how CS contributes to disease patterns later in life. We evaluated the association of delivery mode with postpartum gene expression using a cross-sectional study of 324 mothers who delivered full-term (≥ 37 weeks) singletons. Of these, 181 mothers had a vaginal delivery and 143 had a CS delivery (60 with and 83 without labor). Antimicrobial peptides (AMP) were upregulated in vaginal delivery compared to CS with or without labor. Peptidase inhibitor 3 (PI3), a gene in the antimicrobial peptide pathway and known to be involved in antimicrobial and anti-inflammatory activities, showed a twofold increase in vaginal delivery compared to CS with or without labor (adjusted p-value 1.57 × 10 and 3.70 × 10, respectively). This study evaluates differences in gene expression by delivery mode and provides evidence of antimicrobial peptide upregulation in vaginal delivery compared to CS with or without labor. Further exploration is needed to determine if AMP upregulation provides protection against CS-associated diseases later in life.
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http://dx.doi.org/10.1038/s41598-020-74989-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576122PMC
October 2020

Comparative transcriptomic analysis of contrasting hybrid cultivars reveal key drought-responsive genes and metabolic pathways regulating drought stress tolerance in maize at various stages.

PLoS One 2020 15;15(10):e0240468. Epub 2020 Oct 15.

State Key Laboratory for Crop Improvement and Regulation, Hebei Agricultural University, Baoding, China.

Drought stress is the primary environmental factor that negatively influences plant growth and yield in cereal grain crops such as maize (Zea mays L.). Crop breeding efforts for enhanced drought resistance require improved knowledge of plant drought stress responses. In this study, we applied a 12-day water-deficit stress treatment to maize plants of two contrasting (drought tolerant ND476 and drought sensitive ZX978) hybrid cultivars at four (V12, VT, R1, and R4) crop growth stages and we report key cultivar-specific and growth-stage-specific molecular mechanisms regulating drought stress responses in maize. Based on the transcriptome analysis, a total of 3451 and 4088 differentially expressed genes (DEGs) were identified in ND476 and ZX978 from the four experimental comparisons, respectively. These gene expression changes effected corresponding metabolic pathway responses related to drought tolerance in maize. In ND476, the DEGs associated with the ribosome, starch and sucrose metabolism, phenylpropanoid biosynthesis and phenylpropanoid metabolism pathways were predominant at the V12, VT, R2, and R4 stages, respectively, whereas those in ZX978 were related to ribosome, pentose and glucuronate interconversions (PGI), MAPK signaling and sulfur metabolism pathways, respectively. MapMan analysis revealed that DEGs related to secondary metabolism, lipid metabolism, and amino acid metabolism were universal across the four growth stages in ND476. Meanwhile, the DEGs involved in cell wall, photosynthesis and amino acid metabolism were universal across the four growth stages in ZX978. However, K-means analysis clustered those DEGs into clear and distinct expression profiles in ND476 and ZX978 at each stage. Several functional and regulatory genes were identified in the special clusters related to drought defense response. Our results affirmed that maize drought stress adaptation is a cultivar-specific response as well as a stage-specific response process. Additionally, our findings enrich the maize genetic resources and enhance our further understanding of the molecular mechanisms regulating drought stress tolerance in maize. Further, the DEGs screened in this study may provide a foundational basis for our future targeted cloning studies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240468PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561095PMC
December 2020

Isobaric Tag-Based Protein Profiling across Eight Human Cell Lines Using High-Field Asymmetric Ion Mobility Spectrometry and Real-Time Database Searching.

Proteomics 2021 01 26;21(1):e2000218. Epub 2020 Oct 26.

Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA.

A vast number of human cell lines are available for cell culture model-based studies, and as such the potential exists for discrepancies in findings due to cell line selection. To investigate this concept, the authors determine the relative protein abundance profiles of a panel of eight diverse, but commonly studied human cell lines. This panel includes HAP1, HEK293T, HeLa, HepG2, Jurkat, Panc1, SH-SY5Y, and SVGp12. A mass spectrometry-based proteomics workflow designed to enhance quantitative accuracy while maintaining analytical depth is used. To this end, this strategy leverages TMTpro16-based sample multiplexing, high-field asymmetric ion mobility spectrometry, and real-time database searching. The data show that the differences in the relative protein abundance profiles reflect cell line diversity. The authors also determine several hundred proteins to be highly enriched for a given cell line, and perform gene ontology and pathway analysis on these cell line-enriched proteins. An R Shiny application is designed to query protein abundance profiles and retrieve proteins with similar patterns. The workflows used herein can be applied to additional cell lines to aid cell line selection for addressing a given scientific inquiry or for improving an experimental design.
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http://dx.doi.org/10.1002/pmic.202000218DOI Listing
January 2021

Gut microbiota-derived trimethylamine N-oxide is associated with poor prognosis in patients with heart failure.

Med J Aust 2020 10 22;213(8):374-379. Epub 2020 Sep 22.

Shunde Hospital of Southern Medical University, Foshan (Guangdong), China.

Objective: Gut microbiota-produced trimethylamine N-oxide (TMAO) is a risk factor for cardiovascular events. However, conflicting findings regarding the link between plasma TMAO level and prognosis for patients with heart failure have been reported. We examined the association of plasma TMAO concentration with risk of major adverse cardiac events (MACEs) and all-cause mortality in patients with heart failure.

Study Design: Meta-analysis of prospective clinical studies.

Data Sources: We searched electronic databases (PubMed, EMBASE) for published prospective studies examining associations between plasma TMAO level and MACEs and all-cause mortality in adults with heart failure.

Data Synthesis: Hazard ratios (HRs) with 95% confidence intervals for associations between TMAO level and outcomes were estimated in random effects models. In seven eligible studies including a total of 6879 patients (median follow-up, 5.0 years) and adjusted for multiple risk factors, higher plasma TMAO level was associated with greater risks of MACEs (TMAO tertile 3 v tertile 1: HR, 1.68; 95% CI, 1.44-1.96; per SD increment: HR, 1.26; 95% CI, 1.18-1.36) and of all-cause mortality (TMAO tertile 3 v tertile 1: HR, 1.67; 95% CI, 1.17-2.38; per SD increment: HR, 1.26; 95% CI, 1.07-1.48). Higher TMAO level was also associated with greater risk of MACEs after adjusting for estimated glomerular filtration rate (eGFR; six studies included); however, the heterogeneity of studies in which risk was adjusted for eGFR was significant (I  = 76%).

Conclusions: Elevated plasma TMAO level in patients with heart failure is associated with poorer prognoses. This association is only partially mediated by renal dysfunction.
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http://dx.doi.org/10.5694/mja2.50781DOI Listing
October 2020

An europium functionalized carbon dot-based fluorescence test paper for visual and quantitative point-of-care testing of anthrax biomarker.

Talanta 2020 Dec 12;220:121377. Epub 2020 Jul 12.

College of Chemical Engineering, Zhejiang University of Technology, Hangzhou, 310014, PR China. Electronic address:

We reported Eu(III) functionalized carbon dots (CDs-Eu) as a novel ratiometric fluorescent probe for point-of-care testing (POCT) of dipicolinic acid (DPA), a biomarker of anthrax. The probe was synthesized simply by coordination interaction between Eu(III) ions and the CDs with carboxyl and amino groups. Upon addition of DPA, the intrinsic red luminescence of Eu(III) ions can be sensitized due to the presence of energy transfer when DPA chromophore coordinated with Eu(III) ions. The fluorescence peaking at 530 nm as a reference remained essentially constant, leading to ratiometric fluorescence response toward DPA. This approach exhibited a linearity range from 0.5 nM to 5 μM and a detection limit of 0.8 nM. More Importantly, the combination of probe-based test paper and smartphone provided a convenient approach for visual POCT of DPA with a detection limit of 67 nM, which was lower than other reported test paper for DPA detection. The color of fluorescence gradually changed from green to red as the DPA increases, which can be captured by a smartphone and further quantitatively analyzed with a built-in Color Analyzer App. The satisfactory result of detecting DPA accurately and reliably in real samples by the test paper certified its practicality in POCT of DPA.
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http://dx.doi.org/10.1016/j.talanta.2020.121377DOI Listing
December 2020

Walnut-like MoO with interconnected skeleton and opened muti-channel for fast sodium storage.

Nanotechnology 2020 Nov;31(47):475405

School of Materials Science and Engineering, Shaanxi Key Laboratory of Green Preparation and Functionalization for Inorganic Materials, Shaanxi University of Science and Technology, Xi'an 710021, People's Republic of China.

Molybdenum dioxide (MoO) has attracted lots of theoretical interest as an anode material for sodium ion batteries (SIBs) due to its high theoretical capacity (836 mA h g) and metallic electrical conductivity (1.9 × 10 S cm). The insertion reaction, forming NaMoO and the reversible conversion reaction, forming Mo and NaO from NaMoO contribute capacities of 209 and 627 mA h g, respectively, the latter occupies 75% of the totally theoretical capacity. However, intrinsic slow kinetics in bulk MoO severely restricts the redox conversion reaction. In the present work, a walnut-like MoO architecture (W-MoO) with opened multi-channel and interconnected skeleton was prepared in a tube furnace, providing an interconnected ion/electron dual-pathway, which effectively facilitates Na diffusion and reduces the internal resistance of the cells. The W-MoO anode demonstrates an enhanced reversible sodium storage capacity of 354.7 mA h g at 0.5 A g.
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http://dx.doi.org/10.1088/1361-6528/abaf83DOI Listing
November 2020

Targeting Amyloidogenic Processing of APP in Alzheimer's Disease.

Front Mol Neurosci 2020 4;13:137. Epub 2020 Aug 4.

Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, United States.

Alzheimer's disease (AD) is the most common type of senile dementia, characterized by neurofibrillary tangle and amyloid plaque in brain pathology. Major efforts in AD drug were devoted to the interference with the production and accumulation of amyloid-β peptide (Aβ), which plays a causal role in the pathogenesis of AD. Aβ is generated from amyloid precursor protein (APP), by consecutive cleavage by β-secretase and γ-secretase. Therefore, β-secretase and γ-secretase inhibition have been the focus for AD drug discovery efforts for amyloid reduction. Here, we review β-secretase inhibitors and γ-secretase inhibitors/modulators, and their efficacies in clinical trials. In addition, we discussed the novel concept of specifically targeting the γ-secretase substrate APP. Targeting amyloidogenic processing of APP is still a fundamentally sound strategy to develop disease-modifying AD therapies and recent advance in γ-secretase/APP complex structure provides new opportunities in designing selective inhibitors/modulators for AD.
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http://dx.doi.org/10.3389/fnmol.2020.00137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418514PMC
August 2020

Prognostic Value of Secreted Frizzled-Related Protein 5 in Heart Failure Patients With and Without Type 2 Diabetes Mellitus.

Circ Heart Fail 2020 09 26;13(9):e007054. Epub 2020 Aug 26.

Department of Cardiology, Shunde Hospital (H.Z., X.L., J. Luo, X.H., Y. Hu, Y. Huang), Southern Medical University, Foshan, China.

Background: Patients with heart failure (HF) with diabetes mellitus have distinct biomarker profiles compared with those without diabetes mellitus. SFRP5 (secreted frizzled-related protein 5) is an anti-inflammatory adipokine with an important suppressing role on the development of type 2 diabetes mellitus (T2DM). This study aimed to evaluate the prognostic value of SFRP5 in patients with HF with and without T2DM.

Methods: The study included 833 consecutive patients with HF, 312 (37.5%) of whom had T2DM. Blood samples were collected at presentation, and SFRP5 levels were measured. The primary outcome was the composite end points of first occurrence of HF rehospitalization or all-cause mortality during follow-up.

Results: During median follow-up of 2.1 years, 335 (40.2%) patients in the cohort experienced the composite primary outcome. After adjustment for multiple risk factors, each doubling of SFRP5 level was associated with a 21% decreased risk of primary outcomes in the overall study population (<0.001). Subgroup analyses showed that the association between level of SFPR5 and primary outcomes may be stronger in patients with T2DM (hazard ratio, 0.69 [95% CI, 0.61-0.79]) than in patients without T2DM (hazard ratio, 0.89 [95% CI, 0.79-1.01]; interaction =0.006). Similar associations were observed when taking SFRP5 as a categorical variable. Addition of SFRP5 significantly improved discrimination and reclassification of the incident primary outcomes beyond clinical risk factors and N-terminal pro-B-type natriuretic peptide in all patients with HF and those with T2DM (all <0.01).

Conclusions: SFRP5 is an independent novel biomarker for risk stratification in HF, especially in HF with T2DM.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.007054DOI Listing
September 2020

The significance of the neuregulin-1/ErbB signaling pathway and its effect on Sox10 expression in the development of terminally differentiated Schwann cells .

Int J Neurosci 2020 Aug 24:1-10. Epub 2020 Aug 24.

Department of Anesthesiology, Affiliated Hospital of Qingdao University, Qingdao, P.R China.

Purpose: The purpose of this study was to explore the significance of the neuregulin-1/ErbB signaling pathway and its effect on Sox10 expression in the course of the differentiation of mouse bone marrow mesenchymal stem cells into Schwann-like cells .

Materials And Methods: The experiment was conducted with three groups-control, TAK 165, and HRG-off. In the control group, we used the classical induction method of adding β-ME, RA, FSK, b-FGF, PDGF, and neuregulin (HRG); the cells were collected on the 7 day. Using the same basic protocol as the control group, the specific ErbB2 inhibitor mubritinib (TAK 165) was added to block the neuregulin-1/ErbB pathway in the TAK 165 group, while HRG was not added in the HRG-off group. We detected the degree of differentiation of stem cells into Schwann-like cells by using RT-PCR to examine the expression of Sox10, NRG-1, ErbB2, ErbB3, and ErbB4 and by using immunofluorescence staining to examine the Schwann cell marker S100B, Glial Fibrillary Acidic Protein (GFAP) and P75.

Results: Our results showed that the proliferation of Schwann cells was reduced and apoptosis was increased in the TAK 165 group and the HRG-off group. Sox10 was stably expressed and NRG-1, ErbB2, and ErbB3 increased in the control group. However, the expression of Sox10 in the TAK 165 group was obviously decreased at the end of induced differentiation; meanwhile, the degree of stem cell differentiation also decreased.

Conclusions: the neuregulin-1/ErbB signaling pathway plays an important role in the differentiation of bone marrow mesenchymal stem cells into Schwann-like cells and can promote the maintenance of Sox10 。.
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http://dx.doi.org/10.1080/00207454.2020.1806266DOI Listing
August 2020

The new horizon of liquid biopsy in sarcoma: the potential utility of circulating tumor nucleic acids.

J Cancer 2020 9;11(18):5293-5308. Epub 2020 Jul 9.

Department of bone and soft tissue tumor, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.

The diagnosis, treatment and prognosis of sarcoma are mainly dependent on tissue biopsy, which is limited in its ability to provide a panoramic view into the dynamics of tumor progression. In addition, effective biomarkers to monitor the progression and therapeutic response of sarcoma are lacking. Liquid biopsy, a recent technological breakthrough, has gained great attention in the last few decades. Nucleic acids (such as DNA, mRNAs, microRNAs, and long non-coding RNAs) that are released from tumors circulate in the blood of cancer patients and can be evaluated through liquid biopsy. Circulating tumor nucleic acids reflect the intertumoral and intratumoral heterogeneity, and thus liquid biopsy provides a noninvasive strategy to examine these molecules compared with traditional tissue biopsy. Over the past decade, a great deal of information on the potential utilization of circulating tumor nucleic acids in sarcoma screening, prognosis and therapy efficacy monitoring has emerged. Several specific gene mutations in sarcoma can be detected in peripheral blood samples from patients and can be found in circulating tumor DNA to monitor sarcoma. In addition, circulating tumor non-coding RNA may also be a promising biomarker in sarcoma. In this review, we discuss the clinical application of circulating tumor nucleic acids as blood-borne biomarkers in sarcoma.
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http://dx.doi.org/10.7150/jca.42816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391194PMC
July 2020

A study on the nitrogen removal efficacy of bacterium Acinetobacter tandoii MZ-5 from a contaminated river of Shenzhen, Guangdong Province, China.

Bioresour Technol 2020 Nov 21;315:123888. Epub 2020 Jul 21.

College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China. Electronic address:

Heterotrophic nitrification-aerobic denitrification (HN-AD) has advantages over the traditional nitrogen removal process when removing multiple types of nitrogen in wastewater treatment. Acinetobacter tandoii MZ-5, which is capable of HN-AD, was isolated from the sediment of a polluted river for the first time. It used NH-N, NO-N and NO-N as sole nitrogen sources with maximum removal rates of 2.28, 1.18 and 1.04 mg Lh, respectively. Simultaneous nitrification and denitrification were observed when using mixed N sources and NH-N was preferentially utilized. High nitrogen removal efficiencies (>90%) were achieved under the following conditions: C/N ratio 11-18, pH 6-8, 25-30 °C and dissolved oxygen 7.35-7.66 mg L. Strain MZ-5 was effective at treating wastewater from landfill leachate treatment plants, with NH-N, NO-N and total nitrogen (TN) removal efficiencies of 99.28%, 44.85% and 45.31%, respectively. Thus, strain MZ-5 may be a good candidate for wastewater treatment.
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http://dx.doi.org/10.1016/j.biortech.2020.123888DOI Listing
November 2020

General anesthesia affecting on developing brain: evidence from animal to clinical research.

J Anesth 2020 10 29;34(5):765-772. Epub 2020 Jun 29.

Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun, China.

As the recent update of General anaesthesia compared to spinal anaesthesia (GAS) studies has been published in 2019, together with other clinical evidence, the human studies provided an overwhelming mixed evidence of an association between anaesthesia exposure in early childhood and later neurodevelopment changes in children. Pre-clinical studies in animals provided strong evidence on how anaesthetic and sedative agents (ASAs) causing neurotoxicity in developing brain and deficits in long-term cognitive functions. However pre-clinical results cannot translate to clinical practice directly. Three well designed large population-based human studies strongly indicated that a single brief exposure to general anesthesia (GAs) is not associated with any long-term neurodevelopment deficits in children's brain. Multiple exposure might cause decrease in processing speed and motor skills of children. However, the association between GAs and neurodevelopment in children is still inconclusive. More clinical studies with larger scale observations, randomized trials with longer duration exposure of GAs and follow-ups, more sensitive outcome measurements, and strict confounder controls are needed in the future to provide more conclusive and informative data. New research area has been developed to contribute in finding solutions for clinical practice as attenuating the neurotoxic effect of ASAs. Xenon and Dexmedetomidine are already used in clinical setting as neuroprotection and anaesthetic sparing-effect, but more research is still needed.
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http://dx.doi.org/10.1007/s00540-020-02812-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511469PMC
October 2020

Clinical study of apatinib in the treatment of stage IV osteogenic sarcoma after failure of chemotherapy.

Cancer Biol Med 2020 05;17(2):501-512

Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China.

To analyze the efficacy and safety of apatinib in the treatment of stage IV osteogenic sarcoma after chemotherapy failure through a single-arm, prospective, and open clinical phase II study. Information on 34 patients with stage IV osteogenic sarcoma treated with apatinib after failure of chemotherapy in Tianjin Medical University Cancer Institute and Hospital between September 2015 and December 2019 was collected and analyzed. The participants included 23 males and 11 females, with an average age of 35.24 years (11-73 years). The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), PFS rate (PFR), and overall survival (OS) were evaluated. The treatment-related adverse events (AEs) and safety of apatinib were also evaluated. Of the 34 patients, 33 were able to be evaluated for efficacy. One patient received apatinib treatment for less than one cycle; therefore, only safety analysis was performed. The 12-week clinical evaluation showed that 2 patients had a partial response (PR), 24 patients had stable disease (SD), and 7 patients had progressive disease (PD). The ORR, DCR, and PFR at 12 weeks were 6.06% (2/33), 78.79% (26/33), and 82%, respectively. By the end of the follow-up, 6 patients had SD (18.18%, 6/33), 27 patients had PD (81.82%, 27/33), and 15 patients died because of disease progression (45.45%, 15/33). The ORR was 0 (0/33), the DCR was 18.18% (6/33), and the median PFS (mPFS) was 7.89 months (95% CI: 4.56-11.21). The median OS (mOS) was 17.61 months (95% CI: 10.85-24.37). The most common treatment-related AEs were hand-foot syndrome (35.29%, 12/34), proteinuria (32.35%, 11/34), and hypertension (32.35%, 11/34). Apatinib is effective and well tolerated in stage IV osteogenic sarcoma patients after chemotherapy failure.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2019.0397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309459PMC
May 2020