Publications by authors named "Hongmei Lu"

78 Publications

Photocatalytic reduction-based liquid microjunction surface sampling-mass spectrometry for rapid in situ analysis of aromatic amines originating from azo dyes in packaging papers.

Anal Bioanal Chem 2021 Sep 8. Epub 2021 Sep 8.

College of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan, 410083, People's Republic of China.

A rapid in situ analytical method was developed for the detection of generated carcinogenic aromatic amines from banned azo dyes utilizing a photocatalytic reduction-based liquid microjunction surface sampling (LMJSS)-mass spectrometry (MS) system. We utilized photocatalytic reduction under UV irradiation with TiO as catalyst to have rapid and mild reduction of azo dyes. The reaction conditions were optimized to have complete photocatalytic reduction within 2-5 min in pure methanol at room temperature. TiO was immobilized in the inner wall of the capillaries in the LMJSS system to achieve in situ sampling-online rapid reduction-MS detection for aromatic amines originating from azo dyes in packaging surface. The yields of in-tube photocatalytic reduction were near 100% by delivering the azo dye extracts through the capillary at 1 μL/min under UV irradiation. With this design, in situ analysis was completed within 2 min via direct MS detection and 7 min via liquid chromatography (LC)-MS detection. The detection limits for five aromatic amines originating from four different azo dyes were in the range of 1-17 mg/kg with relative standard deviations (RSDs) < 8.5%. In the application of the new method, four carcinogenic aromatic amines were detected and identified in three commercial packaging materials, and the quantitation results were comparable with those obtained by the conventional chemical reduction-LC-MS method (relative recovery, 81-121%). Moreover, due to the spatial resolution of the present method with a flow probe, MS imaging was achieved demonstrating clear azo dye patterns of a lab-made sample.
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http://dx.doi.org/10.1007/s00216-021-03631-xDOI Listing
September 2021

Per-pixel absolute quantitation for mass spectrometry imaging of endogenous lipidomes by model prediction of mass transfer kinetics in single-probe-based ambient liquid extraction.

Talanta 2021 Nov 25;234:122654. Epub 2021 Jun 25.

College of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan, 410083, PR China.

With the development of mass spectrometry imaging (MSI), techniques providing quantitative information on the spatial distribution have attracted more attentions recent years. However, for MSI of endogenous compounds in bio-samples, the uncertainty of locally varied sampling efficiencies always hinders accurate absolute quantitation. Here single-probe was used for ambient liquid extraction MSI in rat cerebellum, and standards of phosphatidylcholines (PCs) and cerebrosides (CBs) were doped in extraction solvent. The extraction kinetic curves of endogenous lipids in the ambient liquid extraction during probe parking in single pixel of tissue were investigated. From the results, the extraction kinetic curves were varied between different lipid species in different brain regions, resulting in variations of extraction efficiencies between imaging pixels, and calibration with standards deposited in tissue could not compensate for the variations. In our approach, the theoretical kinetic model of ambient liquid extraction was established, and original concentrations of endogenous lipids in each pixel of tissue were predicted by fitting the experimental extraction kinetic curve in each imaging pixel to the model. The experimental data was demonstrated to be well fitted to the kinetic model with R > 0.86, and only with 18-s extraction in each pixel, the original lipid concentrations were predicted accurately with relative errors <23%. With the new method, totally 157 lipids and small metabolites were imaged, and per-pixel quantitation was achieved for 19 PCs and 4 CBs. Compared with conventional quantitative MSI (q-MSI) method, the new q-MSI method had better reproducibility and wider linear range, and produced better contrast in the quantitative images of lipids in brain tissue with less hot spots and noises. The absolute quantitation results by the new method were verified by quantitative LC-MS method with Pearson'r > 0.9 and the slope of the linear fitting line of the correlation plot near 1.
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http://dx.doi.org/10.1016/j.talanta.2021.122654DOI Listing
November 2021

Standardization of Raman spectra using variable penalty dynamic time warping.

Anal Methods 2021 08 13;13(30):3414-3423. Epub 2021 Jul 13.

College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, China.

Raman spectroscopy can provide structural fingerprints to identify molecules by means of spectral library searching. However, it is difficult to share the spectral library between different Raman spectrometers because of the nonlinear displacement in Raman shift. In this study, we propose a Raman spectra Standardization method using Variable Penalty dynamic time warping (RS-VPdtw), which can synchronize the nonlinear displacement between spectra acquired with different spectrometers. We have compared the standardization performance of RS-VPdtw and MWFFT on the spectra of 13 real samples acquired with 6 different spectrometers. The mean spectral similarity of RS-VPdtw and MWFFT increased from 0.79 to 0.97 and 0.91 respectively. Results show that RS-VPdtw is significantly better than MWFFT in Raman spectra standardization. The Raman spectra acquired with different spectrometers can be standardized by RS-VPdtw to search the same spectral library, which can avoid the time-consuming and labor-intensive reestablishment of spectral libraries for different spectrometers. This means that RS-VPdtw is a promising and valuable method to solve the spectra standardization problem in large-scale applications of Raman spectroscopy.
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http://dx.doi.org/10.1039/d1ay00541cDOI Listing
August 2021

Pure Ion Chromatograms Combined with Advanced Machine Learning Methods Improve Accuracy of Discriminant Models in LC-MS-Based Untargeted Metabolomics.

Molecules 2021 May 5;26(9). Epub 2021 May 5.

Yunnan Academy of Tobacco Agricultural Sciences, Kunming 650021, China.

Untargeted metabolomics based on liquid chromatography coupled with mass spectrometry (LC-MS) can detect thousands of features in samples and produce highly complex datasets. The accurate extraction of meaningful features and the building of discriminant models are two crucial steps in the data analysis pipeline of untargeted metabolomics. In this study, pure ion chromatograms were extracted from a liquor dataset and left-sided colon cancer (LCC) dataset by K-means-clustering-based Pure Ion Chromatogram extraction method version 2.0 (KPIC2). Then, the nonlinear low-dimensional embedding by uniform manifold approximation and projection (UMAP) showed the separation of samples from different groups in reduced dimensions. The discriminant models were established by extreme gradient boosting (XGBoost) based on the features extracted by KPIC2. Results showed that features extracted by KPIC2 achieved 100% classification accuracy on the test sets of the liquor dataset and the LCC dataset, which demonstrated the rationality of the XGBoost model based on KPIC2 compared with the results of XCMS (92% and 96% for liquor and LCC datasets respectively). Finally, XGBoost can achieve better performance than the linear method and traditional nonlinear modeling methods on these datasets. UMAP and XGBoost are integrated into KPIC2 package to extend its performance in complex situations, which are not only able to effectively process nonlinear dataset but also can greatly improve the accuracy of data analysis in non-target metabolomics.
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http://dx.doi.org/10.3390/molecules26092715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125400PMC
May 2021

Differences in microbiota between acute and chronic perianal eczema.

Medicine (Baltimore) 2021 Apr;100(16):e25623

Department of Internal Medicine, Beijing Coloproctological Hospital, Beijing Erlonglu Hospital, Beijing, China.

Abstract: Microbiota has been suggested to play a role in patients with intestinal and cutaneous diseases. However, the profiling of perianal eczema microbiota has not been described. We have explored the general profile and possible differences between acute and chronic perianal eczema. A total of 101 acute perianal eczema (APE) and 156 chronic perianal eczema (CPE) patients were enrolled in this study and the perianal microbiota was profiled via Illumina sequencing of the 16S rRNA V4 region.The microbial α-diversity and structure are similar in APE and CPE patients; however, the perianal microbiota of the APE patients had a higher content of Staphylococcus (22.2%, P < .01) than that of CPE patients. Top10 genera accounting for more than 60% (68.81% for APE and 65.47% for CPE) of the whole microbiota, including Prevotella, Streptococcus, and Bifidobacterium, show an upregulation trend in the case of APE without reaching statistically significant differences. This study compared the microbiota profiles of acute and chronic perianal eczema. Our results suggest that the microbiota of acute perianal eczema patients is enriched in Staphylococcus compared with that in the chronic group. Our findings provide data for further studies.
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http://dx.doi.org/10.1097/MD.0000000000025623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078401PMC
April 2021

Quantitative Mass Spectrometry Imaging of Metabolomes and Lipidomes for Tracking Changes and Therapeutic Response in Traumatic Brain Injury Surrounding Injured Area at Chronic Phase.

ACS Chem Neurosci 2021 04 1;12(8):1363-1375. Epub 2021 Apr 1.

College of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan 410083, P. R. China.

Traumatic brain injury (TBI) is a complex disease process that may contribute to temporary or permanent disability. Tracking spatial changes of lipids and metabolites in the brain helps unveil the underlying mechanisms of the disease procession and therapeutic response. Here, the liquid microjunction surface sampling technique was used for mass spectrometry imaging of both lipids and metabolites in rat models of controlled cortical impact with and without XueFu ZhuYu decoction treatment, and the work was focused on the diffuse changes outside the injured area at chronic phase (14 days after injury). Quantitative information was provided for phosphotidylcholines and cerebrosides by adding internal standards in the sampling solvent. With principal component analysis for the imaging data, the midbrain was found to be the region with the largest diffuse changes following TBI outside the injured area. In detail, several phosphatidylcholines, phosphatidylethanolamines, phosphatidic acids, and diacylglycerols were found to be significantly up-regulated particularly in midbrain and thalamus after TBI and XFZY treatment. It is associated with the reported "self-repair" mechanisms at the chronic phase of TBI activated by neuroinflammation. Several glycosphingolipids were found to be increased in most of brain regions after TBI, which was inferred to be associated with neuroinflammation and oxidative stress triggered by TBI. Moreover, different classes of small matabolites were significantly changed after TBI, including fatty acids, amino acids, and purines. All these compounds were involved in 10 metabolic pathway networks, and 6 target proteins of XFZY were found related to the impacted pathways. These results shed light on the molecular mechanisms of TBI pathologic processes and therapeutic response.
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http://dx.doi.org/10.1021/acschemneuro.1c00002DOI Listing
April 2021

Effectiveness of home visiting on patients with hypertension: A systematic review and meta-analysis.

Medicine (Baltimore) 2021 Mar;100(10):e24072

Evidence-Based Nursing Center, School of Nursing of Lanzhou University.

Background: Blood pressure lowering treatments can help prevent cardiovascular disease. However, little is known about the possibility of home visiting programs for hypertension. This study aims to evaluate the effectiveness of home visiting programs on hypertensive patients.

Methods: We systematically reviewed the medical literature and performed a meta-analysis. Five electronic databases were systematically searched from their inception to September 2019. Two reviewers independently assessed the risk of bias of the studies included in the review using tools developed by the Cochrane Collaboration. The meta-analysis was performed using Review Manager software (version 5.3).

Results: Thirteen RCTs with 2674 participants were identified. The home visiting program demonstrated a greater reduction in systolic blood pressure (MD = -5.63, 95% confidence interval (CI): -8.32 to -2.94), diastolic blood pressure (MD = -4.14, 95% CI: -6.72 to -1.56) and waist circumference (MD = -2.61, 95% CI: -3.5, -1.72) during a 6 month intervention. However, there were no significant differences between the groups in terms of body mass index, weight, or blood lipids.

Conclusion: Home visiting programs were associated with improved BP control and reduced blood pressure, which indicate that it might be an effective method for management of hypertension.
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http://dx.doi.org/10.1097/MD.0000000000024072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969236PMC
March 2021

The treatment of syphilis infection in pregnant women and the follow-up investigation and analysis of syphilis infection in children after delivery in Huai'an City.

Panminerva Med 2021 Feb 10. Epub 2021 Feb 10.

Unit of Population Health Information, Huai'an Women and Children's Hospital, Huai'an, China -

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http://dx.doi.org/10.23736/S0031-0808.21.04294-4DOI Listing
February 2021

Maternal and neonatal outcomes of repeated antepartum bleeding in 493 placenta previa cases: a retrospective study.

J Matern Fetal Neonatal Med 2021 Jan 31:1-6. Epub 2021 Jan 31.

Department of Obstetrics and Gynecology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Objective: To explore the effect of antepartum bleeding caused by PP on pregnancy outcomes.

Study Design: We retrospectively analyzed 493 pregnant women complicated with PP. Patients were divided into antepartum repeated bleeding and non-bleeding groups. Maternal characteristics and pregnancy outcomes were compared.

Results: The risk of antepartum hemorrhage was 2.038 times higher when gravidity was 5 (95% CI 1.104-3.760,  = .023). Pregnant women with a history of more than three intrauterine procedures had a 1.968 times higher risk of antepartum hemorrhage (95% CI 1.135-3,412,  = .016) compared to pregnant women without any intrauterine procedures. The risk of antepartum bleeding was found to be decreasing with the pregnancy advancing; When the placenta edge was noted to be over cervical os, the risk of antepartum bleeding was 4.385-fold than the low-lying plcaenta cases (95%CI2.454-8.372,  = .000). In the respect of maternal outcomes, the repeated bleeding group, the risk of emergency surgery was 7.213 times higher than elective surgery (95% CI 4.402-11.817,  = .000). As for the neonatal outcomes, the risk of asphyxia was 2.970 times and the risk of neonatal intensive care unit (NICU) admission was 2.542-fold higher in repeated bleeding group compared to non-bleeding group, respectively.

Conclusions: Obstetricians should be aware of the increased risk of antepartum bleeding especially for ≤34 weeks and placenta edge over cervical os PP patients, they have a higher risk of antepartum bleeding. These women have higher possibility of emergency C-section and need preterm newborn resuscitation.
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http://dx.doi.org/10.1080/14767058.2021.1878495DOI Listing
January 2021

Prediction of Liquid Chromatographic Retention Time with Graph Neural Networks to Assist in Small Molecule Identification.

Anal Chem 2021 02 7;93(4):2200-2206. Epub 2021 Jan 7.

College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, China.

The predicted liquid chromatographic retention times (RTs) of small molecules are not accurate enough for wide adoption in structural identification. In this study, we used the graph neural network to predict the retention time (GNN-RT) from structures of small molecules directly without the requirement of molecular descriptors. The predicted accuracy of GNN-RT was compared with random forests (RFs), Bayesian ridge regression, convolutional neural network (CNN), and a deep-learning regression model (DLM) on a METLIN small molecule retention time (SMRT) dataset. GNN-RT achieved the highest predicting accuracy with a mean relative error of 4.9% and a median relative error of 3.2%. Furthermore, the SMRT-trained GNN-RT model can be transferred to the same type of chromatographic systems easily. The predicted RT is valuable for structural identification in complementary to tandem mass spectra and can be used to assist in the identification of compounds. The results indicate that GNN-RT is a promising method to predict the RT for liquid chromatography and improve the accuracy of structural identification for small molecules.
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http://dx.doi.org/10.1021/acs.analchem.0c04071DOI Listing
February 2021

Shenshuaikang Enema, a Chinese Herbal Remedy, Inhibited Hypoxia and Reoxygenation-Induced Apoptosis in Renal Tubular Epithelial Cells by Inhibiting Oxidative Damage-Dependent JNK/Caspase-3 Signaling Pathways Using Network Pharmacology.

Evid Based Complement Alternat Med 2020 17;2020:9457101. Epub 2020 Nov 17.

Department of Clinical Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.

Background: Acute kidney injury (AKI) is a common clinically critical illness with serious consequences for the patients. Shenshuaikang enema (SE) is a Chinese herbal compound that is used to treat AKI in clinical practice. However, its mechanism of action remains unclear.

Aim: The aim of this study was to investigate the therapeutic effect of SE and explore the molecular mechanisms using network pharmacology and in vitro experiments.

Materials And Methods: The herb-component-target network was constructed based on network pharmacology. The predicted targets and pathways were validated using in vitro experiments. A renal tubular epithelial cell line (HK-2 cells) was exposed to hypoxia and reoxygenation (H/R) using air-tight conditions for five hours and treated with different concentrations of SE (25%, 50%, and 75%) to assess cell viability and apoptosis and determine the optimal experimental dose. Subsequently, H/R-injured HK-2 cells were pretreated with the optimal SE dose and then randomly divided into three groups, the SE, SE-SP600125 (inhibitor of JNK), and SE-NAC (antioxidant) groups. The cell vitality, apoptosis, and death were evaluated using the cell counting kit 8 (CCK8) and carboxyfluorescein succinimidyl ester/propidium iodide (CFSF/PI) staining. The apoptosis-related protein JNK and Caspase-3 were assessed by Western blot. Expression of JNK and Caspase-3 genes was analyzed using real-time quantitative polymerase chain reaction (RT-qPCR).

Results: 123 active components and 226 targets were identified from four herbs that composed the herb-compound-target network based on transcriptomics and network pharmacology analyses. The KEGG pathway analyses revealed that the mitochondrial apoptosis pathway was involved in the therapeutic AKI effects of SE. Cell vitality of H/R-induced HK-2 cells was obviously increased when treating them with SE, and the apoptosis was significantly inhibited, especially in the SE (50%) group at 4 and 12 h after modeling. Pretreatment with antioxidant NAC obviously prevented cell death compared to the SE (50%) group, while no obvious reduction of apoptosis was observed in the SP600125 group. JNK expression level was significantly increased in the SE (50%) group compared to the SP600125 ( < 0.01) and the NAC group ( < 0.05). Caspase-3 was downregulated in the SE (50%) group compared to the SP600125 ( < 0.01) and NAC group ( < 0.05). Caspase-3 activation in the SP600125 group was higher than that in the NAC group ( < 0.05). Moreover, the oxidative damage-dependent JNK/Caspase-3 pathway was identified in the H/R-injured HK-2 cells by inhibiting the JNK activation and oxidative damage.

Conclusions: Our findings suggested that the H/R-triggered apoptosis in HK-2 cells was abrogated by SE by upregulating the oxidative damage-dependent JNK to trigger suppression of Caspase-3.
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http://dx.doi.org/10.1155/2020/9457101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685836PMC
November 2020

Deep-Learning-Assisted multivariate curve resolution.

J Chromatogr A 2021 Jan 13;1635:461713. Epub 2020 Nov 13.

College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, P. R. China. Electronic address:

Gas chromatography-mass spectrometry (GC-MS) is one of the major platforms for analyzing volatile compounds in complex samples. However, automatic and accurate extraction of qualitative and quantitative information is still challenging when analyzing complex GC-MS data, especially for the components incompletely separated by chromatography. Deep-Learning-Assisted Multivariate Curve Resolution (DeepResolution) was proposed in this study. It essentially consists of convolutional neural networks (CNN) models to determine the number of components of each overlapped peak and the elution region of each compound. With the assistance of the predicted elution regions, the informative regions (such as selective region and zero-concentration region) of each compound can be located precisely. Then, full rank resolution (FRR), multivariate curve resolution-alternating least squares (MCR-ALS) or iterative target transformation factor analysis (ITTFA) can be chosen adaptively to resolve the overlapped components without manual intervention. The results showed that DeepResolution has superior compound identification capability and better quantitative performances when comparing with MS-DIAL, ADAP-GC and AMDIS. It was also found that baseline levels, interferents, component concentrations and peak tailing have little influences on resolution result. Besides, DeepResolution can be extended easily when encountering unknown component(s), due to the independence of each CNN model. All procedures of DeepResolution can be performed automatically, and adaptive selection of resolution methods ensures the balance between resolution power and consumed time. It is implemented in Python and available at https://github.com/XiaqiongFan/DeepResolution.
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http://dx.doi.org/10.1016/j.chroma.2020.461713DOI Listing
January 2021

Efficacy and safety of traditional Chinese medicinal enemas for treatment of chronic renal failure: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2020 Oct;99(44):e23002

Department of Nephrology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, PR China.

Background: Chronic renal failure (CRF) is a common kidney disease characterized by a slow and progressive decline in kidney function. Clinical practice suggests that traditional Chinese medicinal enemas have a therapeutic effect on CRF. To assess the therapeutic efficacy and safety of traditional Chinese medicinal enemas in treating CRF, we created a protocol for a systematic review to inform future clinical applications.

Methods: We completed a literature search of all clinical randomized controlled trials evaluating traditional Chinese medicinal enemas on CRF in the following five English and four Chinese databases completed before August 2020: Medline, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Library database, Chinese National Knowledge Infrastructure (CNKI), WANFANE Database, Chinese Scientific and Technological Periodical Database (VIP) and Chinese Biomedical Database (CBM). The primary outcomes evaluated blood urea nitrogen levels, uric acid levels, endogenous creatinine clearance rate, and serum creatinine, and the secondary outcomes included clinical efficacy and adverse effects of treatment. Two independent researchers performed data extraction and quality assessment. RevMan5.3 software was used to assess data quality and bias. This protocol was conducted according to the Preferred Reporting Item for Systematic Review and Meta-analysis Protocol (PRISMA-P) statement.

Results: This study will provide a rational synthesis of current evidence for traditional Chinese medicinal enemas for the treatment of CRF.

Conclusion: This study presents evidence on whether traditional Chinese medicinal enemas are an effective and safe intervention for CRF patients.

Registration Number: INPLASY202080052.
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http://dx.doi.org/10.1097/MD.0000000000023002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598863PMC
October 2020

Neuroprotective Effects of OMO within the Hippocampus and Cortex in a D-Galactose and A -Induced Rat Model of Alzheimer's Disease.

Evid Based Complement Alternat Med 2020 10;2020:1067541. Epub 2020 Oct 10.

Scientific Research Platform, The Second Clinical Medical College, Guangdong Medical University, Dongguan 523808, China.

F.C. How. (Rubiaceae) is a herbal medicine. It has been recorded that its oligosaccharides have neuroprotective properties. In order to understand the oligosaccharides extracted from (OMO), a systematic study was conducted to provide evidence that supports its use in neuroprotective therapies for Alzheimer's disease (AD). AD rat models were prepared with D-galactose and A . The following groups were used in the present experiment: normal control group, sham-operated group, model group, Aricept group, OMO low-dose group, OMO medium-dose group, and OMO high-dose group. The effects on behavioral tests, antioxidant levels, energy metabolism, neurotransmitter levels, and AD-related proteins were detected with corresponding methodologies. AD rats administered with different doses of OMO all exhibited a significant ( < 0.05) decrease in latency and an increase ( < 0.05) in the ratio of swimming distance to total distance in a dose-dependent manner in the Morris water maze. There was a significant ( < 0.05) increase in antioxidant enzyme activities (SOD, GSH-Px, and CAT), neurotransmitter levels (acetylcholine, -GABA, and NE and DA), energy metabolism (Na/K-ATPase), and relative synaptophysin (SYP) expression levels in AD rats administered with OMO. Furthermore, there was a significant ( < 0.05) decrease in MDA levels and relative expression levels of APP, tau, and caspase-3 in AD rats with OMO. The present research suggests that OMO protects against D-galactose and A -induced neurodegeneration, which may provide a novel strategy for improving AD in clinic.
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http://dx.doi.org/10.1155/2020/1067541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569426PMC
October 2020

Fast and Low-Cost Surface-Enhanced Raman Scattering (SERS) Method for On-Site Detection of Flumetsulam in Wheat.

Molecules 2020 Oct 13;25(20). Epub 2020 Oct 13.

College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, China.

The pesticide residues in agri-foods are threatening people's health. This study aims to establish a fast and low-cost surface-enhanced Raman scattering (SERS) method for the on-site detection of flumetsulam in wheat. The two-step modified concentrated gold nanoparticles (AuNPs) acted as the SERS substrate with the aid of NaCl and MgSO. NaCl is served as the activator to modify AuNPs, while MgSO is served as the aggregating agent to form high-density hot spots. The activation and aggregation are two essential collaborative procedures to generate remarkable SERS enhancement and achieve the trace-level detection of flumetsulam. This method exhibits good enhancement effect with an enhancement factor of 10 and wide linear range (5-1000 μg/L). With simple pretreatment, the flumetsulam residue in real wheat samples can be successfully detected with the limit of detection (LOD) down to 0.01 μg/g, which is below the maximum residue limit of flumetsulam in wheat (0.05 μg/g) set in China. The recovery of flumetsulam residue in wheat ranges from 88.3% to 95.6%. These results demonstrate that the proposed SERS method is a powerful technique for the detection of flumetsulam in wheat, which implies the great application potential in the rapid detection of other pesticide residues in various agri-foods.
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http://dx.doi.org/10.3390/molecules25204662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587348PMC
October 2020

Sperm associated antigen 9 promotes oncogenic KSHV-encoded interferon regulatory factor-induced cellular transformation and angiogenesis by activating the JNK/VEGFA pathway.

PLoS Pathog 2020 08 10;16(8):e1008730. Epub 2020 Aug 10.

Department of Microbiology, Nanjing Medical University, Nanjing, People's Republic of China.

Kaposi's sarcoma (KS), caused by Kaposi's sarcoma-associated herpesvirus (KSHV), is a highly angioproliferative disseminated tumor of endothelial cells commonly found in AIDS patients. We have recently shown that KSHV-encoded viral interferon regulatory factor 1 (vIRF1) mediates KSHV-induced cell motility (PLoS Pathog. 2019 Jan 30;15(1):e1007578). However, the role of vIRF1 in KSHV-induced cellular transformation and angiogenesis remains unknown. Here, we show that vIRF1 promotes angiogenesis by upregulating sperm associated antigen 9 (SPAG9) using two in vivo angiogenesis models including the chick chorioallantoic membrane assay (CAM) and the matrigel plug angiogenesis assay in mice. Mechanistically, vIRF1 interacts with transcription factor Lef1 to promote SPAG9 transcription. vIRF1-induced SPAG9 promotes the interaction of mitogen-activated protein kinase kinase 4 (MKK4) with JNK1/2 to increase their phosphorylation, resulting in enhanced VEGFA expression, angiogenesis, cell proliferation and migration. Finally, genetic deletion of ORF-K9 from KSHV genome abolishes KSHV-induced cellular transformation and impairs angiogenesis. Our results reveal that vIRF1 transcriptionally activates SPAG9 expression to promote angiogenesis and tumorigenesis via activating JNK/VEGFA signaling. These novel findings define the mechanism of KSHV induction of the SPAG9/JNK/VEGFA pathway and establish the scientific basis for targeting this pathway for treating KSHV-associated cancers.
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http://dx.doi.org/10.1371/journal.ppat.1008730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446834PMC
August 2020

MicroRNA-1469-5p promotes the invasion and proliferation of pancreatic cancer cells via direct regulating the NDRG1/NF-κB/E-cadherin axis.

Hum Cell 2020 Oct 5;33(4):1176-1185. Epub 2020 Aug 5.

Department of Abdominal Surgery, Linyi Cancer Hospital, Linyi, Shandong, China.

Numerous studies demonstrated that microRNAs (miRNAs) were highly involved in pancreatic cancer development. However, the functional roles of many miRNAs remain elusive in pancreatic cancer. In the present study, we analyzed previous published microarray data and found that miR-1469-5p was one of top upregulated miRNAs in pancreatic tumors. Our further study showed that miR-1469-5p was highly expressed in collected pancreatic tumors and its upregulation was associated with lymph node metastasis and tumors of advanced TNM stage. Functional analysis with miR-1469-5p inhibitor showed that downregulation of miR-1469-5p repressed pancreatic cancer cell proliferation and invasion. Mechanistically, miR-1469-5p directly interacted with metastasis suppressor NDRG1 mRNA and downregulated expression of NDRG1 to activate NF-κB pathway in pancreatic cancer cells. It was also found that miR-1469-5p decreased expression of E-cadherin, a metastasis related gene repressed by NF-κB pathway, in pancreatic cancer cells. Transfection of NDRG1 small interference RNA (siRNA) attenuated the function of miR-1469-5p inhibitor in pancreatic cancer cells. Moreover, miR-1469-5p expression was negatively associated with NDRG1 and E-cadherin mRNA levels in pancreatic tumors. Taken together, miR-1469-5p may exert its oncogenic potential in pancreatic cancer via regulating a NDRG1/NF-κB/E-cadherin axis, suggesting that it may be clinically valuable as a prognostic biomarker of pancreatic cancer.
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http://dx.doi.org/10.1007/s13577-020-00399-7DOI Listing
October 2020

Separation of Glycolipids/Sphingolipids from Glycerophospholipids on TiO Coating in Aprotic Solvent for Rapid Comprehensive Lipidomic Analysis with Liquid Microjunction Surface Sampling-Mass Spectrometry.

Anal Chem 2020 08 28;92(16):11250-11259. Epub 2020 Jul 28.

College of Chemistry and Chemical Engineering, Central South University, Hunan, Changsha 410083, P. R. China.

In lipidomic analysis by direct mass spectrometry (MS), high abundance lipids with high ionizability (such as glycerophospholipids) would cause ion suppression to lipids with poor ionizability and low abundance (such as glycolipids, sphingolipids, or glycerides), which largely limits the detection coverage for lipidomics. In this work, TiO-based liquid microjunction surface sampling (LMJSS) coupled with MS was used for separation of glycerides, phospholipids and glycolipids/sphingolipids in biological samples and rapid analysis of lipids in different classes with high lipidome coverage. We found that, in nonaqueous aprotic solvents, lipids with a glycosyl or sphingosine group could be selectively separated from lipids with a phosphate group (selectivity >10) after being coenriched on TiO by tuning the solvent composition. Accordingly, a selective multistep extraction method was developed by loading the biosamples on TiO slides in neutral aprotic solvent, and sequentially eluting glycerides in pure acetonitrile, glycerophospholipids in 6% ammonia-94% acetonitrile () and glycolipids/sphingolipids in 5% formic acid-95% methanol (/) by LMJSS probe from TiO slide. Each eluate from TiO slide was directly delivered by LMJSS to MS for analysis. The total detection time with three desorption steps would be controlled in 3 min. The method performance for each lipid class was evaluated using lipid standards, including matrix effects (107-128%), RSDs (0.4-16%), linearity (0.98-0.99), detection limits (5-3000 ng/mL), the adsorption equilibrium constants (10-10) and adsorption capacity (1-38 μg/mm) of TiO coated slides to lipids. Finally, the TiO-based-LMJSS-MS method was applied to lipidomic analysis for blood plasma and brain tissue, and compared with direct infusion MS. Results showed that (2-5)-fold more sphingolipids/glycolipids and 40-50 more glycerophospholipids/glycerides were identified in both plasma and brain extract by the new method comparing with direct infusion MS method. Detected lipids were quantified with standard addition calibration method, and the absolute quantitation results measured by TiO-based-LMJSS-MS were verified with that by the traditional LC-MS method (correlation coefficient >0.98, slope of correlation line = 0.87-1.05).
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http://dx.doi.org/10.1021/acs.analchem.0c01870DOI Listing
August 2020

Low bone mineral density due to secondary hyperparathyroidism in the mouse model of Fabry disease.

FASEB Bioadv 2020 Jun 10;2(6):365-381. Epub 2020 Jun 10.

Department of Matrix Medicine Faculty of Medicine Oita University Yufu Oita Japan.

Low bone mineral density (BMD)-diagnosed as osteoporosis or osteopenia-has been reported as a new characteristic feature of Fabry disease; however, the mechanism underlying the development of low BMD is unknown. We previously revealed that a mouse model of Fabry disease [] exhibits impaired functioning of medullary thick ascending limb (mTAL), leading to insufficient Ca reabsorption and hypercalciuria. Here, we investigated bone metabolism in mice without marked glomerular or proximal tubular damage. Low BMD was detected by 20 weeks of age micro-X-ray-computed tomography. Bone histomorphometry revealed that low BMD results by accelerated bone resorption and osteomalacia. Plasma parathyroid hormone levels increased in response to low blood Ca-not plasma fibroblast growth factor 23 (FGF-23) elevation-by 5 weeks of age and showed progressively increased phosphaturic action. Secondary hyperparathyroidism developed by 20 weeks of age and caused hyperphosphatemia, which increased plasma FGF-23 levels with phosphaturic action. The expression of 1α-hydroxylase [synthesis of 1α,25(OH)D] in the kidney did not decrease, but that of 24-hydroxylase [degradation of 1α,25(OH)D] decreased. Vitamin D deficiency was ruled out as the cause of osteomalacia, as plasma 1α,25(OH)D and 25(OH)D levels were maintained. Results demonstrate that secondary hyperparathyroidism due to mTAL impairment causes accelerated bone resorption and osteomalacia due to hyperphosphaturia and hypercalciuria, leading to low BMD in Fabry model mice.
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http://dx.doi.org/10.1096/fba.2019-00080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325589PMC
June 2020

Predicting a Molecular Fingerprint from an Electron Ionization Mass Spectrum with Deep Neural Networks.

Anal Chem 2020 07 25;92(13):8649-8653. Epub 2020 Jun 25.

College of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan 410083, PR China.

Electron ionization-mass spectrometry (EI-MS) hyphenated to gas chromatography (GC) is the workhorse for analyzing volatile compounds in complex samples. The spectral matching method can only identify compounds within the spectral database. In response, we present a deep-learning-based approach (DeepEI) for structure elucidation of an unknown compound with its EI-MS spectrum. DeepEI employs deep neural networks to predict molecular fingerprints from an EI-MS spectrum and searches the molecular structure database with the predicted fingerprints. We evaluated DeepEI with MassBank spectra, and the results indicate DeepEI is an effective identification method. In addition, DeepEI can work cooperatively with database spectral matching and NEIMS (fingerprint to spectrum method) to improve identification accuracy.
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http://dx.doi.org/10.1021/acs.analchem.0c01450DOI Listing
July 2020

An oncogenic viral interferon regulatory factor upregulates CUB domain-containing protein 1 to promote angiogenesis by hijacking transcription factor lymphoid enhancer-binding factor 1 and metastasis suppressor CD82.

Cell Death Differ 2020 12 17;27(12):3289-3306. Epub 2020 Jun 17.

Department of Microbiology, Nanjing Medical University, Nanjing, 211166, P.R. China.

Kaposi's sarcoma (KS), a highly angiogenic and invasive vascular tumor, is the most common AIDS-associated cancer caused by KS-associated herpesvirus (KSHV) infection. We have recently shown that KSHV-encoded viral interferon regulatory factor 1 (vIRF1) contributes to KSHV-induced cell motility (PLoS Pathog. 15:e1007578, 2019). However, the role of vIRF1 in KSHV-induced angiogenesis remains unknown. Here, using two in vivo angiogenesis models including the chick chorioallantoic membrane assay (CAM) and the matrigel plug angiogenesis assay in mice, we show that vIRF1 promotes angiogenesis by upregulating CUB domain (for complement C1r/C1s, Uegf, Bmp1) containing protein 1 (CDCP1). Mechanistically, vIRF1 enhances the expression of transcription factor lymphoid enhancer-binding factor 1 (Lef1) and binds to Lef1 to promote CDCP1 transcription. Meanwhile, vIRF1 degrades metastasis suppressor CD82 through an ubiquitin-proteasome pathway by recruiting E3 ubiquitin ligase AMFR to CD82, which protects CDCP1 from CD82-mediated, palmitoylation-dependent degradation. CDCP1 activates AKT signaling, which is required for vIRF1-induced cell motility but not angiogenesis. Our results illustrate that, by hijacking Lef1 and CD82, vIRF1 upregulates CDCP1 to promote angiogenesis and cell invasion. These novel findings demonstrate the vIRF1 targets multiple cellular proteins and pathways to promote the pathogenesis of KS, which could be attractive therapeutic targets for KSHV-induced malignancies.
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http://dx.doi.org/10.1038/s41418-020-0578-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852890PMC
December 2020

Rapid in situ quantitation of photoinitiators in packaging by two-points kinetic calibration of liquid microjunction surface sampling-mass spectrometry.

Talanta 2020 Aug 9;216:121017. Epub 2020 Apr 9.

College of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan, 410083, PR China.

Absolute quantitation is always a challenge for in situ analysis of solid samples with ambient liquid extraction mass spectrometry due to unknown sampling efficiencies of analytes from complex solid matrices such as commercial packaging materials. Standards were usually dropped onto the sample surface for signal calibration, but the mass transfer of standards would not be the same as analytes distributed in samples. In this work, an in situ quantitation method via liquid microjunction sampling (LMJSS) coupled with mass spectrometry (MS) for photoinitiators (PIs) in packaging was developed without standard spiking. For direct in situ quantitation, mass transfer kinetic model for LMJSS of solid surface was proposed and validated. Results showed that the detection data well fitted the mass transfer model with adjusted R mostly in the range of 0.8-0.9 for 12 PIs in both lab-made mimetic positive samples and commercial packaging samples. According to the mass transfer kinetic model, two-point kinetic calibration method was proposed for calculation of the absolute concentration of PIs in solid samples by LMJSS of the same sample area for two times. The conditions of LMJSS including extraction solvent composition and solvent flowrate were optimized. With the optimized LMJSS-MS method and new calibration method, in situ analysis was done within only 2 min, and detection limits and quantitation limits of 15 PIs in mimetic samples were in the range of 0.06-1.5 mg/m and 0.34-6 mg/m respectively with relative standard deviation (RSDs) in the range of 2%-26%. The quantitation accuracy by the new calibration method for 13 PIs was in the range of 61%-162%. The method was applied to the quantitation of PIs in commercial packaging samples. 6 PIs were detected and identified in four commercial packaging materials, and the quantitation results were comparable with that by traditional solvent extraction-LC-MS method (relative recovery, 63%-127%).
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http://dx.doi.org/10.1016/j.talanta.2020.121017DOI Listing
August 2020

Viral interleukin-6 encoded by an oncogenic virus promotes angiogenesis and cellular transformation by enhancing STAT3-mediated epigenetic silencing of caveolin 1.

Oncogene 2020 06 11;39(23):4603-4618. Epub 2020 May 11.

Department of Microbiology, Nanjing Medical University, Nanjing, 211166, PR China.

Kaposi's sarcoma (KS) caused by oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV) is a highly angiogenic and invasive vascular tumor and the most common AIDS-associated cancer. KSHV-encoded viral interleukin-6 (vIL-6) is implicated in the development of KSHV-induced malignancies; however, the mechanisms underlying vIL-6-induced angiogenesis and tumorigenesis remain undefined. Here, we show that vIL-6 promotes angiogenesis, cell proliferation, and invasion by downregulating caveolin 1 (CAV1) that plays a pivotal and versatile role in multiple cancer-associated processes. Mechanistically, vIL-6 signaling led to the phosphorylation and acetylation of STAT3 that targeted DNA methyltransferase 1 (DNMT1) in a sequential manner. Specifically, the vIL-6-induced phosphorylated form of STAT3 transcriptionally activated DNMT1 expression. Furthermore, vIL-6-induced acetylated form of STAT3 interacted with DNMT1 to form a transcription factor complex that bound to and methylated the CAV1 promoter, leading to CAV1 expression silencing. In fact, downregulation of CAV1 expression resulted in the activation of AKT signaling, promoting cell invasion, and growth transformation induced by KSHV. Finally, genetic deletion of vIL-6 from the KSHV genome abolished KSHV-induced cellular transformation and impaired angiogenesis. Our results reveal that vIL-6 epigenetically silences CAV1 expression to promote angiogenesis and tumorigenesis by regulating the formation of STAT3-DNMT1 complex. These novel findings define a mechanism by which KSHV inhibits the CAV1 pathway and establish the scientific basis for targeting this pathway to treat KSHV-associated cancers.
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http://dx.doi.org/10.1038/s41388-020-1317-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970339PMC
June 2020

Development of a sensitive and rapid UHPLC-MS/MS method for simultaneous quantification of nine compounds in rat plasma and application in a comparative pharmacokinetic study after oral administration of Xuefu Zhuyu Decoction and nimodipine.

Biomed Chromatogr 2020 Sep 16;34(9):e4872. Epub 2020 Jul 16.

Guangzhou Analytical Application Center, Shimadzu Corporation, Guangzhou, China.

Xuefu Zhuyu Decoction (XFZYD) is a traditional Chinese medicine prescription used for the clinical treatment of traumatic brain injury (TBI). The purpose of this work was to develop a sensitive and rapid UHPLC-MS/MS method to simultaneously study the pharmacokinetics of nimodipine and eight components of XFZYD, namely, amygdalin, hydroxysafflor yellow A, rutin, liquiritin, narirutin, naringin, neohesperidin and saikosaponin A, in rats with and without TBI. Multiple reaction monitoring was highly selective in the detection of nine analytes and the internal standard without obvious interference. The calibration curves displayed good linearity (r > 0.99) over a wide concentration range. The mean absolute recoveries of the nine analytes were 85-106%, and all matrix effects were in the range 80-120%. The intra- and inter-day precision and accuracy were acceptable (RSD, <15%; RE%, ±20%). The validated method was successfully applied to compare the pharmacokinetics in four experimental groups, including control rats orally administered XFZYD and TBI model rats orally administered XFZYD, XFZYD and nimodipine, or nimodipine alone. The results showed that herb-drug interactions occurred between XFZYD and nimodipine in the treatment of TBI, nimodipine affected the pharmacokinetics of XFZYD, and XFZYD affected the absorption, distribution and excretion of nimodipine in vivo.
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http://dx.doi.org/10.1002/bmc.4872DOI Listing
September 2020

Quantitative mass spectrometry imaging of amino acids with isomer differentiation in brain tissue via exhaustive liquid microjunction surface sampling-tandem mass tags labeling-ultra performance liquid chromatography-mass spectrometry.

J Chromatogr A 2020 Jun 18;1621:461086. Epub 2020 Apr 18.

College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, Hunan, PR China. Electronic address:

Mass spectrometry imaging (MSI) has been used for localization of various biomolecules in tissues, but it is still challenging to have absolute pixel-to-pixel quantitation of analytes and differentiation of isobaric ions by MSI. In this proof-of-concept study, we present a quantitative MSI method for amino acids with distinguishing their constitutional isomers by exhaustive liquid microjunction surface sampling (LMJSS)-tandem mass tags (TMT) labeling-ultra performance liquid chromatography (UPLC)-MS. TMT6 reagents were used to differentially isotopically label amino acids in extracts from 6 pixels of brain section, resulting in multiplexed analysis of 6 pixels and largely shortening the LC-MSI time. From the results, with TMT labeling, the MS signals of amino acids in brain tissue extract were enhanced by (3-141)-fold. The calibration curves of TMT-labeled amino acids had good linearity in both MS1 and MS2 detection, which is essential for quantitation. A new extraction solvent for LMJSS (10% hexafluoroisopropanol-40% methanol-0.5% acetic acid-water) was developed to improve the extraction efficiencies of polar amino acids from brain tissue. The results showed that the extraction efficiencies of amino acids from different tissue regions were in the range of 75-110% with the new solvent, which made LMJSS an exhaustive sampling. Due to the complete extraction of amino acids from tissue, TMT0-labeled amino acid standards were directly added into the extracts for absolute quantitation. Finally, UPLC-MS was coupled with LMJSS to successfully separate the isobaric labeled amino acids in each pixel, allowing separate imaging of them. The imaging results of amino acid standard pattern demonstrate 500 µm spatial resolution of the MSI method. The brain tissue imaging results showed that the new method enabled quantitative MSI of 11 amino acids including three pairs of isomers, and the quantitation results were highly comparable and correlated with that by traditional bulk extraction-LC-MS method (correlation coefficient = 0.97, the slope of the correlation curve = 0.96).
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http://dx.doi.org/10.1016/j.chroma.2020.461086DOI Listing
June 2020

Corrigendum to "Comprehensive metabolic profiles of seminal plasma with different forms of male infertility and their correlation with sperm parameters'' [J. Pharm. Biomed. Anal. 177 (2020) 112888 / UNSP 112888].

J Pharm Biomed Anal 2020 May 17;184:113167. Epub 2020 Mar 17.

College of Chemistry and Chemical Engineering, Central South University, Hunan, Changsha, 410083, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.jpba.2020.113167DOI Listing
May 2020

Is there a cardiovascular protective effect of aspirin in chronic kidney disease patients? A systematic review and meta-analysis.

Int Urol Nephrol 2020 Feb 9;52(2):315-324. Epub 2019 Dec 9.

No. 1 Department of Nephrology, Hospital of Chengdu University of Traditional Chinese Medicine, No. 37 Shierqiao Road, Chengdu, Sichuan Province, People's Republic of China.

Purpose: To perform a systematic review and meta-analysis to evaluate the cardiovascular prevention effect of aspirin among patients with chronic kidney disease (CKD).

Methods: A comprehensive literature search was conducted in Embase, PubMed, and Cochrane library (up to March 2019) without language limitations. Randomized control trials (RCT) and observational studies that met the inclusion and exclusion criteria were included. Two reviewers independently extracted data, and evaluated study quality using modified Jadad score for RCTs and Newcastle-Ottawa Scale for observational study. A meta-analysis was conducted in the Stata 15.0 software using the DerSimonian and Laird random-effects model.

Results: 1768 references were identified from literature searching. Four RCTs and four cohort studies that reported the cardiovascular prevention outcome of aspirin in CKD patients (38,341 participants) were included in this review. The pooled data revealed that aspirin had no significant prevention effect on cardiovascular events among CKD patients (RR = 0.96, 95% CI, 0.59-1.13). There was also no significant reduction in cardiovascular mortality and all-cause mortality. Although we found no significant increased risk in major bleeding events, there was a statistically significant increased risk of minor bleeding events (RR = 2.57, 95% CI, 1.60-4.13) and renal events (RR = 1.30, 95% CI, 1.02-1.65) for aspirin use.

Conclusion: Our review indicated that aspirin use in CKD patients had no prevention effect on cardiovascular events and no statistically significant reduction in risk of cardiovascular or all-cause mortality, with a significant increased risk of minor bleeding and renal events.
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http://dx.doi.org/10.1007/s11255-019-02350-8DOI Listing
February 2020

Comprehensive metabolic profiles of seminal plasma with different forms of male infertility and their correlation with sperm parameters.

J Pharm Biomed Anal 2020 Jan 21;177:112888. Epub 2019 Sep 21.

College of Chemistry and Chemical Engineering, Central South University, Hunan, Changsha,410083, PR China. Electronic address:

Metabolomics measurements of seminal plasma are widely used in diagnosis and finding of molecular mechanisms of male infertility. However, so far the limitation of metabolome coverage of analytical methods hinders comprehensive metabolite biomarker finding. Moreover, the widely used case-control comparison is not enough to unveil the detailed correlations of the metabolic changes with different sperm abnormalities. In this work, we aimed to have comprehensive metabolic profiling of seminal plasma to find the metabolomics difference between healthy controls and infertility case samples with different semen abnormities by liquid chromatography-mass spectrometry (LC-MS) detection with previously established new sample preparation procedure. Among 624 detected metabolite features, 63 potential biomarkers in various metabolite classes were found for infertility in seminal plasma by multivariate analysis. Interestingly, different infertility forms have different potential biomarkers with few in common, and most of potential biomarkers were found in oligo-astheno-teratospermia samples. To further find the association of the metabolomic changes with specific sperm abnormality, sperm parameters including sperm concentration, sperm deformity rate and sperm motility were also collected, and multivariate linear regression was used to find correlations between sperm parameters and potential biomarkers. Finally, levels of 17 metabolites were found to be significantly correlated with sperm parameters. Most of correlations agreed with previously reported mechanisms of infertility, such as correlation of acylcarnitines with sperm concentration and sperm deformity, and correlation of some antioxidants with sperm deformity rate and sperm motility. Some correlations were reported for the first time, such as negative correlations of isopentenyl pyrophosphate, 2-phosphoglyceric acid and γ-glutamyl-Se-methylselenocysteine with sperm deformity rate, and negative correlation of creatine riboside with sperm concentration. All the potential biomarkers were involved in 14 metabolic pathways playing important role in energy production, antioxidation, hormone regulation and sperm membrane. These results proved previously reported molecular mechanism (such as oxidative stress and energy production) and also gave new possible clues to the pathology of male infertility, which will benefit future etiology, diagnosis and treatment of male infertility.
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http://dx.doi.org/10.1016/j.jpba.2019.112888DOI Listing
January 2020

Enhancing coverage in LC-MS-based untargeted metabolomics by a new sample preparation procedure using mixed-mode solid-phase extraction and two derivatizations.

Anal Bioanal Chem 2019 Sep 14;411(23):6189-6202. Epub 2019 Aug 14.

College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, Hunan, China.

It is a challenge to expand the metabolome coverage of liquid chromatography (LC)-electrospray ionization (ESI) mass spectrometry (MS) based untargeted metabolomics analysis. The limited coverage is attributed to the weak signal of hydroxyl and carboxyl groups in ESI-MS and the limited capacity of LC separation for metabolites with a wide range of polarities. Here a new sample preparation procedure is proposed to solve these problems. Mixed-mode (reversed-phase and anion-exchange) solid-phase extraction sorbents were used to separate metabolites into hydrophilic amine, hydrophobic amine/alcohol, and organic acid groups. Then, alcohols and carboxylic acids in separated groups were tagged with pyridine with use of two derivatization systems for signal enhancement. Finally, hydrophilic amines were analyzed by LC-MS with a hydrophilic interaction LC column, and the two hydrophobic compound groups were analyzed by LC-MS with a C column. From the results for standard samples, the detection limits of the new method are lower than those of the classic solvent extraction-protein precipitation method by 3.3-70 times for five amino acids and by 65-1141 times for five fatty acids. Moreover, the detection limit of this new method is 125 ng mL for cholesterol, which has no signal with the classic method even at 10 μg mL. In seminal plasma samples, 110 more metabolites were identified by this new method than by the traditional solvent extraction-protein precipitation method in positive-mode ESI (new method vs traditional method, 65 vs 22 identified by comparing MS/MS spectra with those of standards, 203 vs 136 identified by searching MS spectra in a published database). Among them, 53 carboxylic acids and 21 alcohols were identified only by the new method, and more hydrophilic amine metabolites, such as amino acids and nucleosides, were identified by the new method than by the classic method. Finally, in application to the study of male infertility, more potential biomarkers of oligoasthenoteratospermic infertility were found with the new method (46 potential biomarkers) than with the classic method (19 potential biomarkers) and previously reported methods (10-30 potential biomarkers). Thus, it is demonstrated that this new sample preparation method expands the detection coverage of LC-MS-based untargeted metabolomics methods and has application potential in biological research.
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http://dx.doi.org/10.1007/s00216-019-02010-xDOI Listing
September 2019
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