Publications by authors named "Lingyun Wang"

132 Publications

A sandwich sensor based on imprinted polymers and aptamers for highly specific double recognition of viruses.

Analyst 2021 May 13. Epub 2021 May 13.

Foshan Green Intelligent Manufacturing Research Institute of Xiangtan University, Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan 411105, China.

Highly selective and highly efficient identification of large viruses has been a major obstacle in the field of virus detection. In this work, a novel sandwich resonance light scattering sensor was designed based on molecularly imprinted polymers (MIPs) and aptamers for the first time. One of the recognition probes was obtained by molecular imprinting using environmentally friendly carbon spheres as carriers and the other by modification of the aptamer that can specifically recognize hepatitis B virus (HBV) on the surface of silicon spheres. In the presence of both probes, an MIP-HBV-aptamer sandwich structure was formed continuously in the system with the increase in HBV concentration, resulting in a strong resonance light scattering response. Finally, satisfactory selectivity and sensitivity were obtained, and the imprinting factor was as high as 7.56, which was higher than that reported in previous works of viral molecular imprinting sensor. In addition, it is of great significance to solve the problem of insufficient selectivity of traditional detection methods for macromolecular targets.
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http://dx.doi.org/10.1039/d1an00155hDOI Listing
May 2021

MTM1 plays an important role in the regulation of zinc tolerance in Saccharomyces cerevisiae.

J Trace Elem Med Biol 2021 Jul 14;66:126759. Epub 2021 Apr 14.

College of Life Sciences, Shanghai Normal University, Shanghai, 200234, China. Electronic address:

Background: Acquisition and distribution of zinc supports a number of biological processes. Various molecular factors are involved in zinc metabolism but not fully explored.

Basic Procedures: Spontaneous mutants were generated in yeast with excess zinc culture followed by whole genome DNA sequencing to discover zinc metabolism related genes by bioinformatics. An identified mutant was characterized through metallomic and molecular biology methods.

Main Findings: Here we reported that MTM1 knockout cells displayed much stronger zinc tolerance than wild type cells on SC medium when exposed to excess zinc. Zn accumulation of mtm1Δ cells was dramatically decreased compared to wild type cells under excessive zinc condition due to MTM1 deletion reduced zinc uptake. ZRC1 mRNA level of mtm1Δ cells was significantly higher than that in the wild-type strain leading to increased vacuolar zinc accumulations in mtm1Δ cells. The mRNA levels of ZRT1 and ZAP1 decreased in mtm1Δ cells contributing to less Zn uptake. The zrc1Δmtm1Δ double knockout strain exhibited Zn sensitivity. MTM1 knockout did not afford resistance to excess zinc through an effect mediated through an influence on levels of ROS. Superoxide dismutase 2 (Sod2p) activity in mtm1Δ cells was severely impaired and not restored through Zn supplementation. Meanwhile, additional Zn showed no significant effect on the localization and expression of Mtm1p.

Principal Conclusions: Our study reveals the MTM1 gene plays an important role in the regulation of zinc homeostasis in yeast cells via changing zinc uptake and distribution. This discovery provides new insights for better understanding biochemical communication between vacuole and mitochondrial in relation to zinc-metabolism.
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http://dx.doi.org/10.1016/j.jtemb.2021.126759DOI Listing
July 2021

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

Phytomedicine 2021 Jun 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
June 2021

An amine-functionalized metal-organic framework and triple-helix molecular beacons as a sensing platform for miRNA ratiometric detection.

Talanta 2021 Jun 8;228:122199. Epub 2021 Feb 8.

Foshan Green Intelligent Manufacturing Research Institute of Xiangtan University, Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan, 411105, China. Electronic address:

Herein, a metal-organic framework (UiO-66-NH) with two functions (intrinsic fluorescence and fluorescence quenching ability) is designed to establish a ratiometric fluorescent platform for high-performance miRNA detection. The use of a fluorescent organic ligand endows the MOF material with a strong intrinsic fluorescence at 440 nm. In the presence of target miRNA, the fluorescence signal of the FAM is restored with the triple helix molecular beacons bind to the target. Using the I/I signal as the output, the prepared ratiometric probe was able to eliminate disturbance caused by the sensing environment. Under the optimal reaction conditions, including buffer pH of 7.4, temperature of 37 °C, and response time of 1 h, the best detection results can be obtained. The ratiometric fluorescence probe presented showed good sensitivity and selectivity for detecting miRNA-203 and the limit of detection was 400 pM with a wide linear range from 1 nM to 160 nM. In addition, this method was applied to diluted human serum and cell lysates, and good detection effect was realized.
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http://dx.doi.org/10.1016/j.talanta.2021.122199DOI Listing
June 2021

Extracellular vesicles and the regulation of tumor immunity: Current progress and future directions.

J Cell Biochem 2021 Feb 16. Epub 2021 Feb 16.

Departments of Pathophysiology, School of Basic Medical Sciences, Nanchang University, Nanchang, Jiangxi, China.

As nano-level information carriers, extracellular vesicles (EVs) contain proteins, DNA or RNA, which maintain the transmembrane transport of biomolecules and the homeostasis of normal cells. EVs can be released by most cell types and absorbed by specific recipient cells, subsequently affecting phenotypic expression. EVs are believed to play an important role in cellular communication, especially in immune cells. During tumor development, EVs of different origins have different effects on the survival and growth of tumor cells. Some tumor cell-derived EVs can mediate tumor immunosuppressive responses by inhibiting the differentiation and maturation of dendritic cells (DCs) and by negatively regulating the expression of T cell receptors, causing tumor cells to escape immune surveillance and proliferate. EVs have therefore become a key component of tumor cell proliferation and metastasis. In contrast, EVs derived from DCs mediate antitumor immune activation by inducing the killing and inhibitory effects of the immune system. This makes it an antigen component of the antitumor response. Integrating the interaction and connection of EVs to immunosuppression and immune response is significant for the application of EVs in clinical practice. Here, we reviewed the research progress on the role of EVs in the immune regulation of tumors.
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http://dx.doi.org/10.1002/jcb.29904DOI Listing
February 2021

The Performance of a Dual-Energy CT Derived Radiomics Model in Differentiating Serosal Invasion for Advanced Gastric Cancer Patients After Neoadjuvant Chemotherapy: Iodine Map Combined With 120-kV Equivalent Mixed Images.

Front Oncol 2020 11;10:562945. Epub 2021 Jan 11.

Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Objectives: The aim was to determine whether the dual-energy CT radiomics model derived from an iodine map (IM) has incremental diagnostic value for the model based on 120-kV equivalent mixed images (120 kVp) in preoperative restaging of serosal invasion with locally advanced gastric cancer (LAGC) after neoadjuvant chemotherapy (NAC).

Methods: A total of 155 patients (110 in the training cohort and 45 in the testing cohort) with LAGC who had standard NAC before surgery were retrospectively enrolled. All CT images were analyzed by two radiologists for manual classification. Volumes of interests (VOIs) were delineated semi-automatically, and 1,226 radiomics features were extracted from every segmented lesion in both IM and 120 kVp images, respectively. Spearman's correlation analysis and the least absolute shrinkage and selection operator (LASSO) penalized logistic regression were implemented for filtering unstable and redundant features and screening out vital features. Two predictive models (120 kVp and IM-120 kVp) based on 120 kVp selected features only and 120 kVp combined with IM selected features were established by multivariate logistic regression analysis. We then build a combination model (ComModel) developed with IM-120 kVp signature and ycT. The performance of these three models and manual classification were evaluated and compared.

Result: Three radiomics models showed great predictive accuracy and performance in both the training and testing cohorts (ComModel: AUC: training, 0.953, testing, 0.914; IM-120 kVp: AUC: training, 0.953, testing, 0.879; 120 kVp: AUC: training, 0.940, testing, 0.831). All these models showed higher diagnostic accuracy (ComModel: 88.9%, IM-120 kVp: 84.4%, 120 kVp: 80.0%) than manual classification (68.9%) in the testing group. ComModel and IM-120 kVp model had better performances than manual classification both in the training (both p<0.001) and testing cohorts (p<0.001 and p=0.034, respectively).

Conclusions: Dual-energy CT-based radiomics models demonstrated convincible diagnostic performance in differentiating serosal invasion in preoperative restaging for LAGC. The radiomics features derived from IM showed great potential for improving the diagnostic capability.
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http://dx.doi.org/10.3389/fonc.2020.562945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874026PMC
January 2021

Spatial Inhibition of Return Affected by Self-Prioritization Effect in Three-Dimensional Space.

Perception 2021 Mar 11;50(3):231-248. Epub 2021 Feb 11.

12582Soochow University, China.

Spatial inhibition of return (IOR) being affected by the self-prioritization effect (SPE) in a two-dimensional plane has been well documented. However, it remains unknown how the spatial IOR interacts with the SPE in three-dimensional (3D) space. By constructing a virtual 3D environment, Posner's classically two-dimensional cue-target paradigm was applied to a 3D space. Participants first associated labels for themselves, their best friends, and strangers with geometric shapes in a shape-label matching task, then performed Experiment 1 (referential information appeared as the cue label) and Experiment 2 (referential information appeared as the target label) to investigate whether the IOR effect could be influenced by the SPE in 3D space. This study showed that when the cue was temporarily established with a self-referential shape and appeared in far space, the IOR effect was the smallest. When the target was temporarily established with a self-referential shape and appeared in near space, the IOR effect disappeared. This study suggests that the IOR effect was affected by the SPE when attention was oriented or reoriented in 3D space and that the IOR effect disappeared or decreased when affected by the SPE in 3D space.
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http://dx.doi.org/10.1177/0301006621992940DOI Listing
March 2021

Nitrogen-doped fluorescence carbon dots as multi-mechanism detection for iodide and curcumin in biological and food samples.

Bioact Mater 2021 Jun 19;6(6):1541-1554. Epub 2020 Nov 19.

Department of Physics, The University of Texas at Arlington, Arlington, TX, 76019-0059, USA.

Iodine ion is one of the most indispensable anions in living organisms, particularly being an important substance for the synthesis of thyroid hormones. Curcumin is a yellow-orange polyphenol compound derived from the rhizome of , which has been commonly used as a spice and natural coloring agent, food additives, cosmetics as well as Chinese medicine. However, excess curcumin may cause DNA inactivation, lead to a decrease in intracellular ATP levels, and trigger the tissue necrosis. Therefore, quantitative detection of iodine and curcumin is of great significance in the fields of food and life sciences. Herein, we develop nitrogen-doped fluorescent carbon dots (NCDs) as a multi-mechanism detection for iodide and curcumin in actual complex biological and food samples, which was prepared by a one-step solid-phase synthesis using tartaric acid and urea as precursors without adding any other reagents. An assembled NCDs-Hg fluorescence-enhanced sensor for the quantitative detection of I was established based on a fluorescence "turn-off-on" mechanism in a linear range of 0.3-15 μM with a detection limit of 69.4 nM and successfully quantified trace amounts of I in water samples and urine sample. Meanwhile, the as-synthesized NCDs also can be used as a fluorescent quenched sensor for curcumin detection based on the synergistic internal filtration effect (IFE) and static quenching, achieving a good linear range of 0.1-20 μM with a satisfactory detection limit of 29.8 nM. These results indicate that carbon dots are potential sensing materials for iodine and curcumin detection for the good of our health.
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http://dx.doi.org/10.1016/j.bioactmat.2020.11.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691164PMC
June 2021

Simple and rapid determination of dioxin in fish and sea food using a highly sensitive reporter cell line, CBG 2.8D.

J Environ Sci (China) 2021 Feb 18;100:353-359. Epub 2020 Aug 18.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100085, China. Electronic address:

Food, especially animal origin food is the main source of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), and dioxin-like polychlorinated biphenyls (dl-PCBs) for human exposure. So, a simple, rapid and cheap bioassay method is needed for determination of dioxins in food samples. In this study, we used a new highly sensitive reporter cell line to determine the concentration of dioxins in 33 fish and seafood samples. The samples were extracted by shaking with water/isopropanol (1:1 v/v) and hexane and cleaned-up by a multi layered silica gel column and an alumina column, then analyzed using CBG 2.8D cell line. We compared the results obtained from the CBG 2.8D cell assay to those obtained from conventional High-Resolution Gas Chromatography-High Resolution Mass Spectrometry (HRGC-HRMS) analysis. Good correlations were observed between these two methods (r=0.93). While the slope of regression line was 1.76, the bioanalytical equivalent (BEQ) values were 1.76 folds higher than WHO-TEQ values and the conversion coefficient was 0.568 (the reciprocal of 1.76). In conclusion, CBG 2.8D cell assay was an applicable method to determine dioxins levels in fish and sea food samples.
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http://dx.doi.org/10.1016/j.jes.2020.07.006DOI Listing
February 2021

Predicting Chemotherapeutic Response for Far-advanced Gastric Cancer by Radiomics with Deep Learning Semi-automatic Segmentation.

J Cancer 2020 18;11(24):7224-7236. Epub 2020 Oct 18.

Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

To build a dual-energy computed tomography (DECT) delta radiomics model to predict chemotherapeutic response for far-advanced gastric cancer (GC) patients. A semi-automatic segmentation method based on deep learning was designed, and its performance was compared with that of manual segmentation. This retrospective study included 86 patients with far-advanced GC treated with chemotherapy from September 2016 to December 2017 (66 and 20 in the training and testing cohorts, respectively). Delta radiomics features between the baseline and first follow-up DECT were modeled by random forest to predict the chemotherapeutic response evaluated by the second follow-up DECT. Nine feature subsets from confounding factors and delta radiomics features were used to choose the best model with 10-fold cross-validation in the training cohort. A semi-automatic segmentation method based on deep learning was developed to predict the chemotherapeutic response and compared with manual segmentation in the testing cohort, which was further validated in an independent validation cohort of 30 patients. The best model, constructed by confounding factors and texture features, reached an average AUC of 0.752 in the training cohort. Our proposed semi-automatic segmentation method was more time-effective than manual segmentation, with average saving-time of 11.2333 ± 6.3989 minutes and 9.9889 ±5.5086 minutes in the testing cohort and the independent validation cohort, respectively (both p < 0.05). The predictive ability of the semi-automatic segmentation was also better than that of the manual segmentation both in the testing cohort and the independent validation cohort (AUC: 0.728 vs. 0.687 and 0.828 vs. 0.749, respectively). DECT delta radiomics serves as a promising biomarker for predicting chemotherapeutic response for far-advanced GC. Semi-automatic segmentation based on deep learning shows the potential for clinical use with increased reproducibility and decreased labor costs compared to the manual version.
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http://dx.doi.org/10.7150/jca.46704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646171PMC
October 2020

Quantitative acetylome analysis reveals involvement of glucosyltransferase acetylation in Streptococcus mutans biofilm formation.

Environ Microbiol Rep 2021 Apr 24;13(2):86-97. Epub 2020 Nov 24.

State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Streptococcus mutans (S. mutans) effectively utilizes dietary sucrose for the exopolysaccharide productions, which are mostly synthesized by the effects of glucosyltransferases (Gtfs). In the present study, the acetylome of S. mutans was identified and quantitative acetylome analysis of the bacterial biofilm growth (SMB) was compared with that of planktonic growth (SMP). The dynamic changes of protein acetylation were quantified using the integrated approach involving TMT labeling and Kac affinity enrichment followed by high-resolution mass spectrometry-based quantitative proteomics. In total, 973 acetylation sites in 445 proteins were identified, among which 617 acetylation sites in 302 proteins were quantitated. The overall analysis indicated that 22.7% of proteins were acetylated. Among the quantified proteins in SMB, the acetylation degree of lysine in 56 sites increased, while that of lysine decreased in 52 sites. In the acetylome of S. mutans, six significantly enriched motifs were identified and obtained including Kac****K, KacF, Kac****R, KacY, KacH, F*Kac. In addition, KEGG pathway-based enrichment analysis indicated significant enrichments in glycolysis/gluconeogenesis, and RNA degradation. Particularly, most downregulated acetylated lysine proteins were glucosyltransferase-SI, glucosyltransferase-I, and glucosyltransferase-S in S. mutans biofilm, which probably reveals a switch-off mechanism for the regulation of glucosyltransferases function during the biofilm development.
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http://dx.doi.org/10.1111/1758-2229.12907DOI Listing
April 2021

A novel and efficient chromophore reaction based on a lactam-fused aza-BODIPY for polyamine detection.

Anal Chim Acta 2020 Oct 25;1135:38-46. Epub 2020 Aug 25.

Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Ministry of Agriculture Key Laboratory of Animal Nutrition and Feed Science in South China, Guangzhou, 510641, China. Electronic address:

Polyamines (such as spermine, spermidine) play important roles in biomedical and food field. The elevated polyamines have been proposed to serve as target analytes for monitoring meat spoilage. Because of structural similarity and low concentration of polyamines in real samples, it is exceedingly challenging to design and develop sensitive probes for visual detection of polyamines. To address this issue, a highly efficient probe was reported based on a newly developed chromophore reaction between lactam-fused aza-BODIPY (abbreviation: LAB) and polyamines by virtue of unique multiple amino groups character of polyamines. This chromophore reaction includes a kinetic-controllable reaction of a B-N bond cleavage by polyamines followed by a fast hydrolysis reaction to yield much smaller conjugated molecules. With 130 nm hypsochromic shift of the absorption peak and up to 99% fluorescence quenching within 1 min, LAB can be used as a highly sensitive fluorescent probe for detection of polyamines solution and monitoring fish spoilage with synchronous colorimetric and fluorescent changes.
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http://dx.doi.org/10.1016/j.aca.2020.08.031DOI Listing
October 2020

Comparative Evaluation of Prophylactic SIV Vaccination Modalities Administered to the Oral Cavity.

AIDS Res Hum Retroviruses 2020 12 27;36(12):984-997. Epub 2020 Oct 27.

Department of Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.

Attempts to develop a protective human immunodeficiency virus (HIV) vaccine have had limited success, especially in terms of inducing protective antibodies capable of neutralizing different viral strains. As HIV transmission occurs mainly via mucosal surfaces, HIV replicates significantly in the gastrointestinal tract, and the oral route of vaccination is a very convenient one to implement worldwide, we explored three SIV vaccine modalities administered orally and composed of simian immunodeficiency virus (SIV) DNA priming with different boosting immunogens, with the goal of evaluating whether they could provide lasting humoral and cellular responses, including at mucosal surfaces that are sites of HIV entry. Twenty-four Cynomolgus macaques (CyM) were primed with replication-incompetent SIV DNA provirus and divided into three groups for the following booster vaccinations, all administered in the oral cavity: Group 1 with recombinant SIV gp140 and heat-labile toxin adjuvant dmLT, Group 2 with recombinant SIV-Oral Poliovirus (SIV-OPV), and Group 3 with recombinant SIV-modified vaccinia ankara (SIV-MVA). Cell-mediated responses were measured using blood, lymph node, rectal and vaginal mononuclear cells. Significant levels of systemic and mucosal T-cell responses against Gag and Env were observed in all groups. Some SIV-specific plasma IgG, rectal and salivary IgA antibodies were generated, mainly in animals that received SIV DNA + SIV-MVA, but no vaginal IgA was detected. Susceptibility to infection after SIV challenge was similar in vaccinated and nonvaccinated animals, but acute infection viremia levels were lower in the group that received SIV DNA + SIV-MVA. Nonvaccinated CyM maintained central memory and total CD4 T-cell levels in the normal range during the 5 months of postinfection follow-up as did the vaccinated animals, precluding evaluation of vaccine impact on disease progression. We conclude that the oral cavity vaccination tested in these regimens can stimulate cell-mediated immunity systemically and mucosally, but humoral response stimulation was limited with the doses and the vaccine platforms used.
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http://dx.doi.org/10.1089/AID.2020.0157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703093PMC
December 2020

Comprehensive profiling of protein lysine acetylation and its overlap with lysine succinylation in the Porphyromonas gingivalis fimbriated strain ATCC 33277.

Mol Oral Microbiol 2020 12 5;35(6):240-250. Epub 2020 Oct 5.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.

Porphyromonas gingivalis is a pathogen closely associated with periodontal and systemic infections. Recently, lysine acetylation (Kac) and lysine succinylation (Ksuc) have been identified in bacterial proteins with diverse biological and pathological functions. The Ksuc of P. gingivalis ATCC 33277 has been characterized in our previous work, and here, we report the systematic analysis of Kac and its crosstalk with Ksuc in this bacterium. A combination of the affinity enrichment by the acetyl-lysine antibody with highly sensitive LC-MS/MS was used to identify the lysine-acetylated proteins and sites in P. gingivalis ATCC 33277. A total of 1,112 lysine-acetylated sites matching 438 proteins were identified. These proteins involved in several cellular processes, especially those proteins related to protein biosynthesis and central metabolism had a high tendency to be lysine acetylated. Moreover, lysine sites flanked by tyrosine, phenylalanine, and histidine in the +1 position, as well as residue lysine in position +4 to +5, were the targets of Kac. Additionally, proteins involved in adhesins, gingipains, black pigmentation, and oxidative stress resistance were identified as substrates of Kac. Collectively, these results suggest Kac may play a critical role in the regulation of physiology and virulence of P. gingivalis. Furthermore, we discovered that, Ksuc and Kac were extensively overlapped in P. gingivalis ATCC 33277, especially in proteins related to ribosomes and metabolism. This study provides a significant beginning for further investigating the role of Kac and Ksuc in the pathogenicity of P. gingivalis.
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http://dx.doi.org/10.1111/omi.12312DOI Listing
December 2020

A Remote-Controlled Robotic System with Safety Protection Strategy Based on Force-Sensing and Bending Feedback for Transcatheter Arterial Chemoembolization.

Micromachines (Basel) 2020 Aug 25;11(9). Epub 2020 Aug 25.

Department of Mechanical and Electrical Engineering, Xiamen University, Xiamen 361102, China.

Transcatheter arterial chemoembolization (TACE) is the common choice of non-open surgery for hepatocellular carcinoma (HCC) now. In this study, a simple TACE robotic system of 4-degree-of-freedom is proposed to get higher accuracy and stability of the surgery operation and reduce X-ray exposure time of the surgeons. The master-slave control strategy is adopted in the robotic system and a customized sigmoid function is designed to optimize the joystick control of the master-slave robotic control system. A force-sensing module is developed to sense the resistance of the guide wire in linear delivery motion and an auxiliary bending feedback method based on constraint pipe with a film sensor is proposed. With two force-sensing methods, the safety strategy of robotic motion with 9 different motion constraint coefficients is given and a human-computer interface is developed. The TACE robot would monitor the value of the force sensor and the analog voltage of the film sensor to adopt the corresponding motion constraint coefficient in every 10 ms. Vascular model experiments were performed to validate the robotic system, and the results showed that the safety strategy could improve the reliability of the operation with immediate speed constraint and avoid potential aggressive delivery.
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http://dx.doi.org/10.3390/mi11090805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569875PMC
August 2020

Autoinhibition of TRPV6 Channel and Regulation by PIP2.

iScience 2020 Aug 8;23(9):101444. Epub 2020 Aug 8.

National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan, Hubei 430068, China. Electronic address:

Transient receptor potential vanilloid 6 (TRPV6), a calcium-selective channel possessing six transmembrane domains (S1-S6) and intracellular N and C termini, plays crucial roles in calcium absorption in epithelia and bone and is involved in human diseases including vitamin-D deficiency, osteoporosis, and cancer. The TRPV6 function and regulation remain poorly understood. Here we show that the TRPV6 intramolecular S4-S5 linker to C-terminal TRP helix (L/C) and N-terminal pre-S1 helix to TRP helix (N/C) interactions, mediated by Arg470:Trp593 and Trp321:Ile597 bonding, respectively, are autoinhibitory and are required for maintaining TRPV6 at basal states. Disruption of either interaction by mutations or blocking peptides activates TRPV6. The N/C interaction depends on the L/C interaction but not reversely. Three cationic residues in S5 or C terminus are involved in binding PIP2 to suppress both interactions thereby activating TRPV6. This study reveals "PIP2 - intramolecular interactions" regulatory mechanism of TRPV6 activation-autoinhibition, which will help elucidating the corresponding mechanisms in other TRP channels.
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http://dx.doi.org/10.1016/j.isci.2020.101444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452202PMC
August 2020

Cross-Linked Networks in Poly(propylene carbonate) by Incorporating (Maleic Anhydride/-1,2,3,6-Tetrahydrophthalic Anhydride) Oligomer in CO/Propylene Oxide Copolymerization: Improving and Tailoring Thermal, Mechanical, and Dimensional Properties.

ACS Omega 2020 Jul 9;5(28):17808-17817. Epub 2020 Jul 9.

School of Chemistry and Chemical Engineering, Key Laboratory of Functional Molecular Engineering of Guangdong Province, South China University of Technology, Guangzhou 510641, China.

Poly(propylene carbonate) (PPC) from CO and propylene oxide (PO) has wide potential applications as a degradable "plastic". However, the thermal stability and mechanical properties of PPC cannot meet most of the application requirements. Herein, we focus on improving these properties. A (maleic anhydride/-1,2,3,6-tetrahydrophthalic anhydride) (MA/THPA) oligomer containing several cyclocarboxylic anhydride groups, which can copolymerize with PO, has been readily synthesized and used as the third comonomer to prepare PPC with cross-linked networks. The gel contents increase from 16 to 42% with increasing MA/THPA oligomer feed contents from 0.5 to 4 wt % of PO. The formation of cross-linked networks in PPC greatly improves the thermal, mechanical, and dimensional properties. The 5% weight-loss degradation temperature increases from 217 °C to nearly 290 °C before and after cross-linking, which ensures that PPC does not decompose in melt processing. The tensile strength of the copolymer is in the range of 22.2-44.3 MPa with elongation at break of 11-312%. The maximum tensile strength is improved by 143% compared to that of PPC. When the MA/THPA oligomer feed is above 3 wt % of PO, the hot-set elongation of the copolymer at 65 °C decreases more than 10 times when compared with that of PPC, and the permanent deformation is close to 0, while it is 145% for PPC. The dimensional stability is improved sharply. It can overcome the cold flow phenomenon of PPC. The improvement of the above comprehensive properties is of great significance to the practical application of PPC in various fields.
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http://dx.doi.org/10.1021/acsomega.0c02608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379107PMC
July 2020

Association between carotid intima media thickness and small dense low-density lipoprotein cholesterol in acute ischaemic stroke.

Lipids Health Dis 2020 Jul 28;19(1):177. Epub 2020 Jul 28.

Department of Neurology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, No. 15 Jiefang Road, Fancheng District, Xiangyang, 441000, People's Republic of China.

Background: Intima-media thickness (IMT) and small dense low-density lipoprotein cholesterol (sdLDL-C) have been reported to be related to atherosclerosis and stroke. This study is trying to explore the association between IMT and sdLDL-C in Chinese acute ischaemic stroke (AIS) subjects.

Methods: This study enrolled total 368 consecutive AIS patients and 165 non-AIS controls from November 2016 to February 2019. Mean IMT and carotid plaques were measured by using carotid ultrasonography method. Blood glucose and lipid parameters were measured by using an automatic biochemical instrument. SdLDL-C was detected by using the Lipoprint LDL system. IMT > 1.0 mm was defined as increased IMT. Plaque stability based on the nature of the echo was determined by ultrasound examination. Risk factors for IMT were identified by using multivariate logistic regression analysis. A logistic regression model was established to predict AIS risk. Python software (Version 3.6) was used for the statistical analysis of all data.

Results: The carotid IMT, proportion of plaques, and the sdLDL-C, triglycerides (TG) and glucose levels were obviously higher in AIS patients than those in controls. SdLDL-C level in the IMT thickening group was higher than that in the normal IMT group. SdLDL-C and total cholesterol (TC) were risk factors for IMT, while sdLDL-C was an independent risk factor. The IMT value of the unstable plaque group was markedly higher than that of the stable plaque group. The predictive value of IMT for AIS was better than that of low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) but not as good as that of sdLDL-C. A logistic regression model was established to predict AIS risk. Additionally, carotid IMT and sdLDL-C were closely related to AIS severity and outcomes.

Conclusions: SdLDL-C and TC were risk factors for increased IMT, while sdLDL-C was an independent risk factor. A prediction model based on IMT and other variables was established to screen the population with high AIS risk.
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http://dx.doi.org/10.1186/s12944-020-01353-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388515PMC
July 2020

Carbon Dot-Based Composite Films for Simultaneously Harvesting Raindrop Energy and Boosting Solar Energy Conversion Efficiency in Hybrid Cells.

ACS Nano 2020 Aug 29;14(8):10359-10369. Epub 2020 Jul 29.

Department of Mechanical and Automation Engineering, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.

Energy harvesting has drawn worldwide attention as a sustainable technology, while combining several approaches in a single device to maximize the overall energy output holds great promise to offer valuable technologies able to alleviate the energy crisis. Here, we present a hybrid cell composed of a silicon solar cell and a water-droplet-harvesting triboelectric nanogenerator (WH-TENG) with the capacity of harvesting both solar and raindrop energies. A transparent and solution processable carbon dot-based composite film is introduced as a dual-functional layer, acting as the transmittance enhancement layer of the solar cell as well as an ionic conductor of the WH-TENG. At an optimal loading of carbon dots in the composite, the significant enhancement of transmittance in visible spectral range increases the short-circuit current density of the solar cell, which results in an increase of its power conversion efficiency from 13.6% to 14.6%. In addition, the transparent WH-TENG consisting of fluorinated ethylene propylene as a triboelectrification layer can generate a maximum power of 13.9 μW by collecting raindrop energy. This study provides a promising strategy to boost the energy conversion through multiple sources with the aid of a dual-functional layer for enhancing solar cell performance as well as harvesting raindrop energy.
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http://dx.doi.org/10.1021/acsnano.0c03986DOI Listing
August 2020

Modulating the molecular configuration by varying linking bridge for double-anchored dye-sensitized solar cells.

J Chem Phys 2020 Jun;152(24):244708

State Key Laboratory of Luminescent Materials and Devices, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510641, China.

Three novel metal-free organic dyes (TPTZ1, TPTZ2, and TPTZ3) with an A-D-π-D-A configuration were synthesized and applied for dye-sensitized solar cells (DSSCs). The relationship between the photovoltaic properties and the different connection bridges of these organic dyes was studied systematically, showing that a strategical variation on the linkage ways of dithiophene can obviously affect the twisted degree of backbone and, thus, have a great effect on inhibiting the intermolecular aggregation. Compared with a bulky rigid group substituted on TPTZ3, introducing flexible side chains at suitable sites on the TPTZ1 and TPTZ2 seems to be a more effective strategy to achieve high photoelectric performance for double anchoring dye. Indeed, the DSSCs based on TPTZ2 exhibit a high efficiency of 7.50%, reaching 99% of an N719-based standard cell at the same condition. This study provides a new approach for highly efficient anti-aggregation organic sensitizers.
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http://dx.doi.org/10.1063/5.0009177DOI Listing
June 2020

Association between variants in vitamin D-binding protein gene and vitamin D deficiency among pregnant women in china.

J Clin Lab Anal 2020 Sep 14;34(9):e23376. Epub 2020 Jun 14.

Department of Gynaecology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, China.

Background: The prevalence of vitamin D deficiency and insufficiency is extremely high in pregnant women worldwide. However, the association between single nucleotide polymorphisms (SNPs) in vitamin D metabolic pathway genes and 25-hydroxyvitamin D (25(OH)D) concentration among Chinese pregnant women is seldom reported. The risk of adverse neonatal outcomes due to maternal vitamin D deficiency has not been well investigated.

Methods: A total of 815 pregnant women and 407 infants were enrolled in this study. Serum 25(OH)D concentration was detected. DNA was extracted from the maternal blood for genotyping genetic SNPs in vitamin D pathway. An XGBoost model was established based on SNPs combined with external variables.

Results: Mean serum 25(OH)D level was 15.67 ± 7.98 ng/mL among the pregnant women. Seventy-five percent of pregnant women had 25(OH)D deficiency in China. SNPs of GC (rs17467825, rs4588, rs2282679, rs2298850, and rs1155563) were significantly associated with maternal 25(OH)D concentration. The influence of variants of rs17467825, rs4588, rs2282679, and rs2298850 on maternal 25(OH)D might be modified by vitamin D supplementation and sunshine exposure. An XGBoost model was established for monitoring 25(OH)D status in pregnant women and provided clinical advice to reduce the risk of 25(OH)D deficiency. Mothers with 25(OH)D deficiency hinted a risk for macrosomia.

Conclusion: A high prevalence of vitamin D deficiency in China has been confirmed. A clinical model was established to guide pregnant women to supplement vitamin D according to genotype. Furthermore, we suggest the effect of maternal vitamin D status on the risk of macrosomia.
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http://dx.doi.org/10.1002/jcla.23376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521226PMC
September 2020

Pyridinium-substituted tetraphenylethylene salt-based photosensitizers by varying counter anions: a highly efficient photodynamic therapy for cancer cell ablation and bacterial inactivation.

J Mater Chem B 2020 06;8(24):5234-5244

Department of Physics, The University of Texas at Arlington, Arlington, Texas 76019, USA.

Cancer and bacterial infection seriously threaten the health of human beings. The development of an image-guided photosensitizer with a "Two-in-One" function that can be simultaneously used for both efficient cancer cell ablation and rapid bacterial inactivation is highly in demand. In this project, we designed and prepared two aggregation-induced emission luminogens (AIEgens) (called TPEPy-I and TPEPy-PF6) with a strong electron push-pull effect. They have a near-infrared (NIR) emission, a high 1O2 quantum yield up to 0.93 and a fluorescence turn-on effect in mitochondria. Upon white light irradiation, the two mitochondria-targeting AIEgens exhibit a highly efficient photodynamic ablation of HeLa cells as well as excellent photodynamic inactivation of both Gram-positive S. aureus and Gram-negative E. coli. The time-dependent density functional theory (TD-DFT) results indicate that compared to TPEPy-PF6, TPEPy-I can easily produce the triplet state that is a prerequisite for 1O2 formation. Moreover, the positive effect of iodide anions gives TPEPy-I a higher photodynamic efficacy in cancer cell ablation and bacterial inactivation as compared with TPEPy-PF6.
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http://dx.doi.org/10.1039/d0tb00888eDOI Listing
June 2020

Characteristics of oral methicillin-resistant Staphylococcus epidermidis isolated from dental plaque.

Int J Oral Sci 2020 05 9;12(1):15. Epub 2020 May 9.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, China.

The oral microbial community is widely regarded as a latent reservoir of antibiotic resistance genes. This study assessed the molecular epidemiology, susceptibility profile, and resistance mechanisms of 35 methicillin-resistant Staphylococcus epidermidis (MRSE) strains isolated from the dental plaque of a healthy human population. Broth microdilution minimum inhibitory concentrations (MICs) revealed that all the isolates were nonsusceptible to oxacillin and penicillin G. Most of them were also resistant to trimethoprim (65.7%) and erythromycin (54.3%). The resistance to multiple antibiotics was found to be largely due to the acquisition of plasmid-borne genes. The mecA and dfrA genes were found in all the isolates, mostly dfrG (80%), aacA-aphD (20%), aadD (28.6%), aphA3 (22.9%), msrA (5.7%), and the ermC gene (14.3%). Classical mutational mechanisms found in these isolates were mainly efflux pumps such as qacA (31.4%), qacC (25.7%), tetK (17.1%), and norA (8.6%). Multilocus sequence type analysis revealed that sequence type 59 (ST59) strains comprised 71.43% of the typed isolates, and the eBURST algorithm clustered STs into the clonal complex 2-II(CC2-II). The staphyloccoccal cassette chromosome mec (SCCmec) type results showed that 25 (71.43%) were assigned to type IV. Moreover, 88.66% of the isolates were found to harbor six or more biofilm-associated genes. The aap, atlE, embp, sdrF, and IS256 genes were detected in all 35 isolates. This research demonstrates that biofilm-positive multiple-antibiotic-resistant ST59-SCCmec IV S. epidermidis strains exist in the dental plaque of healthy people and may be a potential risk for the transmission of antibiotic resistance.
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http://dx.doi.org/10.1038/s41368-020-0079-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210960PMC
May 2020

Host-Guest Complexation of Monoanionic and Dianionic Guests with a Polycationic Pillararene Host: Same Two-Step Mechanism but Striking Difference in Rate upon Inclusion.

J Phys Chem Lett 2020 Mar 27;11(6):2021-2026. Epub 2020 Feb 27.

State Key Laboratory of Luminescent Materials and Devices, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, China.

Supramolecular dynamic studies provide the most direct information to elucidate the binding mechanisms of the systems and yet are underdeveloped in pillararene chemistry. Herein, we describe the first real-time study on the binding dynamics of a water-soluble per-substituted pillar[5]arene (H1) with pentanesulfonate (G1) and butane-1,4-disulfonate (G2). Both the host-guest complexes were formed via a two-step process. The first step, equilibrated within 1 ms for both guests, was associated with the formation of a 1:1 exclusion complex, and the second step was the conversion of this exclusion complex to the inclusion complex. Threading and dethreading processes in the second step for G2 were at least a million times slower than for G1. Kinetics results reveal that for H1, complexation with a charged guest may follow the same "two-step" mechanism regardless of the number of charged moieties in the guests and the rate of the complexation. This study may advance the mechanistic understanding necessary for further development of functional supramolecular systems.
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http://dx.doi.org/10.1021/acs.jpclett.0c00277DOI Listing
March 2020

Association of Small Dense Low-Density Lipoprotein Cholesterol with Stroke Risk, Severity and Prognosis.

J Atheroscler Thromb 2020 Dec 15;27(12):1310-1324. Epub 2020 Feb 15.

Qinhuangdao No.1 Hospital.

Aim: To investigate the association of small dense low-density lipoprotein cholesterol (sdLDL-C) and acute ischemic stroke (AIS) in terms of risk, severity, and outcomes. Prediction models were established to screen high-risk patients and predict prognosis of AIS patients.

Methods: We enrolled in this study 355 AIS patients and 171 non-AIS controls. AIS was subtyped according to TOAST criteria, and the severity and outcomes of AIS were measured. Blood glucose and lipid profiles including total cholesterol, triglyceride, and lipoproteins were measured in all patients using automatic measure. Lipoprotein subfractions were detected by the Lipoprint LDL system.

Results: As compared with the non-AIS control group, the AIS group had higher sdLDL-C levels. Pearson correlation analysis revealed that the sdLDL-C level and risk of AIS, especially non-cardioembolic stroke, were positively correlated. The area under the curve of sdLDL-C for AIS risk was 0.665, better than that of other lipids. Additionally, the sdLDL-C level was significantly correlated with AIS severity and bad outcomes. A logistic regression model for assessing the probability of AIS occurrence and a prognostic prediction model were established based on sdLDL-C and other variables.

Conclusions: Elevated levels of sdLDL-C were associated with a higher prevalence of AIS, especially in non-cardioembolic stroke subtypes. After adjustment for other risk factors, sdLDL-C was found to be an independent risk factor for AIS. Also, sdLDL-C level was strongly associated with AIS severity and poor functional outcomes. Logistic regression models for AIS risk and prognosis prediction were established to help clinicians provide better prevention for high-risk subjects and monitor their prognosis.
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http://dx.doi.org/10.5551/jat.53132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840160PMC
December 2020

Genotypes and zoonotic potential of in edible bullfrogs () in China.

Int J Parasitol Parasites Wildl 2020 Apr 13;11:103-107. Epub 2020 Jan 13.

College of Animal Science, Tarim University, Alar, Xinjiang, 843300, China.

, an obligate intracellular pathogen of the intestinal epithelium, is commonly identified in humans and many other animals and is ubiquitous in water sources and the environment generally. To determine the molecular prevalence of in edible bullfrogs () and evaluate the possibility of its potential zoonotic transmission to humans via food or water, the intestinal contents of 295 bullfrogs were intermittently collected from two open markets in Aksu, China. The samples were screened for the internal transcribed spacer by polymerase chain reaction amplifications, revealing that 20.7% (61/295) of them were infected with , with no significant differences found between the two sampling locations ( > 0.05). Twenty-two different genotypes were identified, including one known genotype (EbpC) and 19 novel ones (named BLC1 to BLC19). The zoonotic genotype EbpC was identified in most of the -positive samples (65.6%, 40/61). The remaining genotypes were identified in either one or three samples each. Our phylogenetic analysis showed that 20 of the genotypes belonged to Group 1. As far as we are aware, this is the first report of infections in edible bullfrogs. Our findings suggest that can be maintained in edible bullfrogs and potentially transmitted via food or water. It is possible that these amphibians are unsuspected zoonotic reservoirs of .
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http://dx.doi.org/10.1016/j.ijppaw.2020.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005328PMC
April 2020

Fushen Granule, A Traditional Chinese Medicine, ameliorates intestinal mucosal dysfunction in peritoneal dialysis rat model by regulating p38MAPK signaling pathway.

J Ethnopharmacol 2020 Apr 23;251:112501. Epub 2019 Dec 23.

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

Ethnopharmacological Relevance: Fushen Granule (FSG) is a Chinese medicinal formular prepared in hospital to treat intestinal mucosal dysfunction induced by peritoneal dialysis (PD). However, the mechanisms of this formular has not been studied yet.

Aim Of The Study: The present study was designed to investigate the effect of FSG against intestinal dysfunction during PD treatment and explore the potential mechanisms using a rat PD model.

Methods And Methods: In the present study, the effect of FSG on improving intestinal mucosal architecture injury was intuitively shown by hematoxylin-eosin staining, the serum levels of DAO and D-lactate were measured to evaluate the intestinal permeability by the DAO Assay Kit and D-Lactic Acid ELISA Kit. The expression of the intestinal mucosal barrier related inflammation factor by real-time PCR. The main effective constituents of FSG were characterized by UPLC/Q-TOF analysis, and the targets and pathways of the constituents were predicted via TCMSP database and IPA. the activation of p38MAPK signaling pathway by western blotting.

Results: HE staining results showed that FSG protected against intestinal mucosal injury in pathology in PD rats. FSG decreased the intestinal mucosal permeability by increasing the transepithelial electrical resistance (TER) level and decreasing the intestinal clearance of fluorescein-isothiocyanate dextran (FD4) and the level of D-lactate and diamine oxidase (DAO). FSG significantly decreased the expression of ICAM-1, IL-1β, iNOS and TNF-α, and further inhibited the activation of p38MAPK signaling pathway via down-regulating the expression of P-p38MAPK and up-regulating the expression of DUSP1, occludin, and ZO-1.

Conclusion: This study demonstrates that FSG ameliorated intestinal mucosal dysfunction in PD by decreasing expression of pro-inflammatory cytokines and inhibiting the activation of p38MAPK signaling pathway. The results provide a promising basis for the alternative medicine treatment of intestinal mucosal dysfunction in PD.
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http://dx.doi.org/10.1016/j.jep.2019.112501DOI Listing
April 2020

Effect of Enhanced Squeezing Needle Structure on the Jetting Performance of a Piezostack-Driven Dispenser.

Micromachines (Basel) 2019 Dec 5;10(12). Epub 2019 Dec 5.

Department of Mechanical and Electrical Engineering, Xiamen University, 4221-134th Xiang'an South Road, Xiamen 361102, China.

Advanced dispensing technology is urgently needed to improve the jetting performance of fluid to meet the requirements of electronic product integration and miniaturization. In this work, an on-off valve piezostack-driven dispenser was used as a study object to investigate the effect of needle structure on jetting performance. Based on fluid dynamics, we investigated nozzle cavity pressure and jet velocity during the dispensing process using theoretical simulation for needles with and without a side cap. The results showed that the needle with a side cap had larger jet velocity and was capable of generating 8.27 MPa of pressure in the nozzle cavity, which was 2.39 times larger than the needle without a side cap. Further research on the influence of the nozzle and needle structural parameters showed that a nozzle conic angle of 85°-105°, needle conic angle of 10°-35°, and side clearance of 0.1-0.3 mm produced a dispenser with a large jet velocity and stable performance, capable of dispensing microscale droplets. Finally, a smaller droplet diameter of 0.42 mm was achieved in experiments using a glycerol/ethanol mixture, with a variation range of ± 4.61%.
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http://dx.doi.org/10.3390/mi10120850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953060PMC
December 2019

Molecular insights into the effect of an apoptotic raft-like bilayer on the conformation and dynamics of calreticulin.

Biochim Biophys Acta Biomembr 2020 02 6;1862(2):183146. Epub 2019 Dec 6.

Department of Biomedical Engineering, The University of Alabama at Birmingham, Birmingham, AL 35294, United States. Electronic address:

Cell surface calreticulin (CRT) can mediate apoptotic cells removal by binding and activating LDL receptor-related protein (LRP1). Phosphatidylserine (PS) lipids in the inner leaflet of the cell membrane are externalized and become exposed in cholesterol (CHOL)-rich membrane raft-like microdomain during apoptosis and co-localized with cell surface CRT. How the apoptotic raft-like membrane microdomain affects the structure and dynamics of CRT, further affecting CRT binding with LRP1 to signal apoptotic-cell clearance, remains unknown. In this study, we investigate the interactions between CRT and raft-like bilayers with or without POPS lipids with molecular dynamics simulations. In addition, the effect of an apoptotic raft bilayer on the binding between CRT and thrombospondin-1 (TSP1), a ligand of CRT on the cell surface to signal focal adhesion disassembly, was also investigated. Results of single CRT interactions with raft-like bilayers show that PS lipids in apoptotic raft-like bilayer increased the interactions between CRT and lipid bilayer, which enhanced the conformational stability and increased dynamical motion of CRT. The microscopic and mesoscopic properties of apoptotic raft-like bilayer were altered by the binding of CRT with lipid bilayer. Results of CRT-TSP1 complex interactions with raft-like bilayers show that the binding free energy between TSP1 and CRT was reduced in apoptotic raft-like bilayer environment. This study provides molecular and structural insight into the effect of an apoptotic raft-like bilayer on the conformation and dynamics of CRT, which could enrich our understanding of CRT-mediated apoptotic-cell clearance and focal adhesion disassembly.
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http://dx.doi.org/10.1016/j.bbamem.2019.183146DOI Listing
February 2020

IDO inhibitor synergized with radiotherapy to delay tumor growth by reversing T cell exhaustion.

Mol Med Rep 2020 Jan 12;21(1):445-453. Epub 2019 Nov 12.

Departments of Pathophysiology and Immunology, School of Basic Medical Sciences, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.

Previous studies suggest that radiotherapy (RT) can induce immune activation, which not only reduces the progression of tumors, but also causes the release of tumor antigens. The combination of RT and immune checkpoint blockade, such as the inhibition of programmed cell death 1 (PD‑1) and programmed cell death ligand 1 (PD‑L1), has been demonstrated to yield impressive response rates. However, a substantial proportion of patients develop resistance such therapies. Previous studies have shown that indoleamine 2,3‑dioxygenase (IDO) causes T cell exhaustion and increased formation of regulatory T cells (Tregs), upregulating the expression of inhibitory receptors and ligands. Therefore, the application of IDO inhibitors combined with RT may have a synergistic effect by relieving immunosuppression. Lewis lung cancer cell‑bearing mice were treated with the IDO inhibitor 1‑methyl‑tryptophan (1MT) and/or 10 Gy RT. Tumor size was measured every day, flow cytometry was performed to measure the expression of dendritic cell (DC) maturation markers, inhibitory receptors, ligands, cytotoxic T cells and Treg phenotypic markers. Reverse transcription‑quantitative PCR was used to evaluate the mRNA expression levels of IDO, PD‑L1, PD‑1, T cell immunoglobulin domain and mucin domain 3 (TIM‑3), B‑ and T‑lymphocyte attenuator (BTLA) and galectin‑9. Compared with the control group, treatment with 1MT or RT reduced tumor growth, however, the combination therapy was more effective than either treatment alone. Flow cytometry showed the upregulation of CD80, CD86 and the major histocompatibility complex II in spleen DCs and the concurrent downregulation of CD4, CD25 and forkhead box protein P3 in lymphocytes in the treatment groups. Compared with the control group, inhibitory receptors and ligands that affect DCs and T cells were observed, expression levels of PD‑L1, PD‑1, TIM‑3, BTLA and galectin‑9 are decreased in treatment group compared with control. IDO inhibition synergized with RT to downregulate Tregs, inhibitory receptors and ligands to prevent T cell exhaustion. By activating DCs and T cells, this combination therapy may strongly enhance antitumor immunity and inhibit tumor progression.
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http://dx.doi.org/10.3892/mmr.2019.10816DOI Listing
January 2020